200525160 nbde-part-i-biochem-review-and-study-guide

2003 Biochemistry Review for the National Boards Part I Page 1 of 35
©2003 Gene C. Lavers, Ph.D.
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Examination Specifications (2002)1
Building Blocks of Life Course (41)
I. Physical-Chemical Principles (3)
A. Basic principles (2)
B. Applied principles (1)
II. Biological Compounds (9)
A. Sugars and carbohydrates (1)
B. Amino Acids and proteins (2 )
C. Lipids (1)
D. Nucleic Acids and metabolism (1)
E. Interdisciplinary clinical/cross correlation (4)
III. Metabolism (13)
A. Bioenergetics (1)
B. Enzymology (1)
C. Catabolism (2)
D. Anabolism (2)
E. Regulation (2)
F. Interdisciplinary clinical/cross correlation (5)
---25 ---
IV. Molecular Biology (8)
A. DNA/RNA and protein synthesis (4 )
B. Genetic engineering (2)
C. Interdisciplinary clinical/cross correlation (2)
XIV. Nutrition (8)
A. Nutrients/minerals (3)
1. Requirements (1)
2. Functions (2)
B. Interdisciplinary and clinical/cross correlation (2)
---16 of 25 ---
---9 of 25 ---
Biochemistry in other D1 Courses (13)
V. Connective Tissues (8) (in Basic Tissues)
A. Soft tissue (2)
B. Hard Tissue/calcification (3)
C. Interdisciplinary and clinical/cross correlation (3)
VI. Membranes (4) (most in Cell Organelles )

A. Structure (1)
B. Function (1)
VII. Nervous System (9) (most in Organ Systems)
A. General properties (2)
B. Central nervous system (1)
C. Autonomic nervous system (1)
D. Somatic nervous system (with reflexes) (2)
E. Special senses (1)
F. Interdisciplinary and clinical/cross correlation (2)
VIII. Muscle (6) ()
A. Skeletal (2) metabolism and myoglobin
B. Smooth (1)
C. Cardiac (1)
D. Interdisciplinary and clinical/cross correlation (3)
IX. Circulation (9) (in Basic Tissues/clotting/gas transport
A. Fluid content and dynamics (2)
B. Coagulation (1)
C. Cardiodynamics and electrophysiology (2)
C. Regulation (1)
X. Respiration (6) (in Basic Tissues)
A. Mechanical aspects (1)
B. Gas exchange and transport (1)
C. Regulation (1)
XI. Renal (6) (see Organ Systems)
A. Functional anatomy (1)
B. Blood flow and filtration (1)
C. Reabsorption and secretion (1) metabolites
XII. Acid-Base Balance (1) (in Organ Systems)
XIII. Digestion (5) (in Organ Systems)
A. Neuromuscular (1)
B. Secretions (1) enzymes
C. Absorption (1)
D. Regulation (1)
E. Interdisciplinary and clinical/cross correlation (1)
XV. Endocrines (8) (in Organ Systems)
A. Pituitary/hypothalamus (1)
B. Reproduction (1)
C. Signaling systems (2) insulin/glucagon & cAMP
D. Pancreas/parathyroid (1)
E. Adrenal/thyroid (1)

Integrated Biochemistry Review and Study Questions
To assist you in reviewing Biochemistry for the Part I National Boards, review questions were prepared and are accompanied
by suggested study or thought questions in red text. Additionally, written answers - as endnotes - are provided to foster easier
review rather than new learning. To see the answer, move the mouse cursor over the endnote number (exponent) and the
endnote pops up. Greek letters, super/subscripts formatting are lost in the popup note, so consult the actual endnote as needed.
[Additional information is within brackets in grey tone, which is also lost in the popup note.].
The TOPIC headings (centered) and their SUBTOPIC headings (left margin) are also in gray scale. Topics in Building
Blocks of Life course are in blue text. Other topics taught in the previous traditional biochemistry course are in other D1
courses, these other topics are in green text. Many subtopics can not be included in a short 50 question format, so the related
study questions attempt to expand the subtopics in the questions. Not all answers (*) are reviewed or discussed in the endnote
material.
PHYSICAL-CHEMICAL PRINCIPLES (3)
BASIC PRINCIPLES
1. Which of the following functional groups behaves as a weak acid, i.e., dissociate a proton in aqueous solution, at
physiological pH?
A. R—CH2—R'
B. RCH2—OH
C. R—NH3
+
* D. R—COOH
E. Ph—OH
Related study questions.
[1] What is physiological pH?2
What is a weak acid compared to a strong acid?3
[2] Identify each functional group above, which can dissociate at physiological pH; and why4
?
[3] Why is the pKa of –COOH and –NH2 on the α-carbon of amino acids about 1-2 pH unit higher and lower, respectively5
?
2. Which of the following pairs of compounds is INCORRECTLY matched with its respective type of stereoisomerism?
A. D- and L–glyceraldehyde : absolute configuration
B. α– and β-glucose : anomer pair
C. glucose and mannose : epimers
D. cis- and trans–fumarate : geometric isomers
* E. ribose and glucose : diastereomers
[1] How many configurations can an asymmetric tetrahedral carbon and a chiral carbon have6
? How many different
configurations do all of the asymmetric carbons (C*) contribute in a sugar?7
How many C* in aldoses8
; ribose, glucose,
and mannose; in ketoses9
: ribulose, xylulose, fructose?
[2] Regarding carbons C1
–C5
or C1
–C6
, which chiral carbons in those sugars define pairs of anomers (α/β)10
, epimers11
(e.g.,
glucose and mannose) , D/L-sugar families12
(e.g., D/L-glucose).
[3] How many of the asymmetric carbon atoms of these sugars rotate polarized light, i.e., are optically active?13
If a D-sugar
always give a (+) optical rotation does the corresponding mirror image L-sugar always give a (–) rotation?14
Is there any
consistent relationship between the asymmetrical tetrahedral carbons and the direction (+ or –) of optical light rotation
properties?15
[4] What are meso stereoisomers versus diastereoisomer?16
Cite an example17
.
APPLIED PRINCIPLES
3. Which thermodynamic parameter deals with randomness and disorder?
A. enthalpy
* B. entropy
C. free energy
D. activation energy
E. potential energy
[1] What is the meaning of each the terms listed18
?
[2] What is the significance of random disorder versus specified order in biological systems19
?

[3] Is entropy increased or decreased by such processes as glycogenesis, fatty acid synthesis, protein synthesis, DNA and RNA
synthesis20
compared to others (e.g.: glycogenolysis, β-oxidation, proteolysis, and hydrolysis of DNA and RNA)21
?
BIOLOGICAL COMPOUNDS (9)
SUGARS AND CARBOHYDRATES
4. The C1
of ribose and glucose has all of the following properties EXCEPT ONE. Which is the EXCEPTION?
A. Anomeric carbon forms α/β racemic mixture.
B. Acyl aldehyde groups react with primary and secondary alcohols, amines, and mercaptans.
* C. D/L isomers define the specific optical rotation.
D. In solution, mutarotation of either pure intramolecular hemiacetal yields an equilibrium mixture of
α/β anomers.
E. Forms acetal ribosides and glucosides, respectively, that can’t mutarotate.
Related study questions
[1] How do planar aldehydes and ketones groups give rise to an asymmetric tetrahedral carbon racemic pair22
?
[2] Compare the total number of asymmetric centers in the open-chain and cyclic-forms of aldoses ribose, deoxyribose,
glucose, mannose, galactose have (and ketose fructose)23
.
[3] Mutarotation may or may not invert C1
configuration of cyclic-aldoses, but when C1
is in an α(1-4) acetal linkage no
inversion is possible, for example, for the C1
of the α−glucosyl moiety of maltose (glucosyl−α(1-4)-glucose), or for the
β−glucosyl moiety of cellobiose (glucosyl−β(1-4)-glucose) or for the β−ribosyl moiety of adenosine (N−β−ribosyl
adenine); explain.24
[4] Does this acetal type of chemistry have significance for RNA and DNA stability and function?25
AMINO ACIDS AND PROTEINS
5. All of the following are characteristic of amino acids EXCEPT.
A. The α-carbon (C2) is a chiral center (except for glycine).
* B. All migrate to the cathode in an electric field at physiological pH.
C. They have side chains with different physical and chemical properties.
D. Most can form dipolar ions (zwitterions) at physiological pH.
E. Only a repertoire of 20 amino acids are incorporated into proteins.
[1] How do D- and L-amino acids relate to the D- and L-glyceraldehyde reference compounds?26
[2] What functional groups are present in the side-chains of free amino acids that account for their ionization to zwitterion
forms at physiological pH?27
[3] How do some amino acids acquire a net (+1) or (–) charge in aqueous solution?28
[4] What changes in net charge occur in free amino acids if the pH is adjusted from pH 2 to pH 12 that effects their net charge
and therefore their electrophoretic mobility at different pHs?29
[5] Which amino acids are always incorporated into proteins compared to others in the body that arise either as pathway
metabolites (e.g., ornithine in the urea cycle) or as a result of posttranslational modification of in a protein (e.g.,
hydroxyproline from proline hydroxylation in collagen chains?30
6. Which amino acid is INCORRECTLY matched to its side-chain?
A. lysine : ε−amino–aliphatic hydrocarbon chain
B. isoleucine : branched aliphatic hydrocarbon chain
* C. tyrosine : aromatic imidazole
D. glutamic acid : δ–carboxylate –aliphatic hydrocarbon chain
E. methionine : γ-methylmercapto–aliphatic hydrocarbon chain
[1] How is the tertiary (3°) and quaternary (4°) structure of proteins affected by the properties of the amino acid side-chains
(polar, apolar, acidic, basic, neutral, aliphatic, aromatic, and reactivity)?31
[2] Which amino acids are usually in the hydrophobic interior and which are on the hydrophilic exterior in contact with water
when the primary sequence folds to yield the functional 3D-structure?32
[3] Which amino acids are most often modified with sugars and lipids posttranslationally that are then involved in non-bonded
versus covalent cross-links in complex structures?33
LIPIDS
7. Select the INCORRECT statement about lipids.

A. Lipids are small nonpolar molecules extracted by organic solvents.
B. Most of our fat is stored as triglyceride droplets in adipose tissue cells.
C. Phospholipids are the major class of lipids in membranes.
D. ABO-blood group antigens are glycosphingolipids (glycolipids).
* E. Most fatty acids are present as free acids in cells.
[1] What are the major classes of lipids and their constituent compounds found in the body?34
[2] What are some of the key properties of lipids that make them suitable for energy storage, as thermal and electrical
insulators, and appropriate for membrane partitions?35
[3] What core component distinguishes phospholipids from sphingolipids36
; what carbohydrate components of
glycosphingolipids constitute the ABO blood group antigens on red blood cells?37
NUCLEIC ACIDS AND METABOLISM
8. Which one of the following compounds DOES NOT supply atoms for the synthesis of the purine ring system?
A. glycine
B. aspartate
C. N10
-formyl-THFA
D. CO2
* E. S-adenosyl methionine (SAM)
[1] What are the substrates and sequence of incorporation of atoms or fragments into the purine ring system during de novo
synthesis of IMP?38
[2] How is IMP converted to AMP or GMP?39
Why are some purine and pyrimidine reaction steps coupled to ATP hydrolysis?40
[3] Choices C to E are compounds involved in 1-carbon fragment metabolism for the synthesis of which nucleotides?41
INTERDISCIPLINARY CLINICAL/CROSS CORRELATIONS
9. All of the following EXCEPT one correctly completes the statement below. Which is the EXCEPTION?
Oxidation of glutathione (GSH) to disulfide GSSG in red blood cells protects proteins from oxidative damage by:
A. O2•–
.
B. reactive oxygen species.
* C. NADP+
.
D. methylglyoxal.
[1] What is glutathione (GSH), which of its functional groups has an antioxidant role against various reactive oxygen species
(ROS), and which two cells-types have GSH levels that reach 6-8 mM?42
[2] The glyoxalase pathway in all cells protects proteins against oxidative insult from what small glucose fragments originating
from glycolysis?43
[3] What is the chemical relationship of oxygen, oxygen superoxide, hemoglobin, methemoglobin, and Heinz bodies?44
10. Gout disease and Lesch-Nyhan syndrome are due to deficiency of one or two enzymes in purine metabolism and can
be treated with allopurinol. Which statement about allopurinol biochemistry is INCORRECT?
A. Allopurinol decreases the rate of oxidation of purines to urate.
* B. Allopurinol increases urate solubility.
C. Allopurinol inhibits xanthine oxidase.
D. Allopurinol acts as a suicide inhibitor.
E. Allopurinol increases the opportunity for purine salvage.
[1] What two salvage enzymes and their reactions are deficient in purine metabolism that leads to hyperuricemia and excessive
accumulation of poorly soluble urate in the joints of cooler extremities and kidney stones in middle-aged men?45
[2] What molybdenum-requiring enzyme is inhibited by allopurinol? Why is allopurinol an example of a suicide inhibitor?46
[3] Account for the effect of allopurinol in regulating purine biosynthesis and alleviating symptoms?47
11. Which of the following represents the chemical substance that is an additional reserve of energy for muscle
contraction?
A. Glycogen
B. Lactic acid

C. Acetyl CoA
* D. Creatine phosphate
E. Adenosine triphosphate
[1] What is the primary source of energy for muscle contraction?48
[2] What compound is the secondary backup energy reserve the muscle cell used to regenerate ATP, which is rapidly depleted
during short bursts of contraction thereby giving time for activation of glycogenolysis to supply glucose thereafter?49
[3] Why is creatine phosphate a high energy molecule like ATP?50
[4] What dead-end catabolite of creatine phosphate is excreted from the muscle cell into plasma and then into urine that betrays
bursts of vigorous muscle contraction?51
12. A severe pyruvate carboxylase (PCase) deficiency would likely produce TCA cycle dysfunction and very low ATP
levels in cells because:
A. pyruvate concentration is too low.
B. lactic acid concentration is too low.
C. of insufficient fatty acid synthesis for membrane formation.
D. of respiratory acidosis from ongoing rapid breathing.
* E. of insufficient oxaloacetic acid (OAA) to condense with acetyl CoA to form citrate.
[1] What are anaplerotic reactions and why is pyruvate carboxylase so critical for normal TCA cycle activity?52
[2] Why do high pyruvate and lactate levels occur in PCase deficiency; why would that lead to lactic acidosis?53
[3] Why does lipogenesis increase significantly (up to several fold during this deficiency);54
and what pathway maintains the
supply of NADPH required?55
METABOLISM (13)
BIOENERGETICS
13. Hexokinase __1__ the free energy from ATP hydrolysis to phosphorylate glucose thereby driving an unfavorable
endergonic reaction with an spontaneous __2__ reaction.
A. 1 = uncouples 2 = endergonic
B. 1 = uncouples 2 = exergonic
C. 1 = couples 2 = endergonic
* D. 1 = couples 2 = exergonic
Helpful hints
[1] What is the significance of free energy change (∆G) compared to free energy (G); what is enthalpy change, in biological
systems and why is ∆G more useful as a measure of metabolic achievement?56
[2] If ∆G°´ = – 7.3 kcal/mol for ATP hydrolysis (Rx I): ATP + H2O –> ADP + Pi; and if ∆G°´ = + 3.3 kcal/mol for the
phosphorylation of glucose using a phosphate (Rx II): glucose + P –> G-6-P; then account for the – 3 kcal/mol net ∆G°´
that results from the coupled reaction (Rx III) of hexokinase: glucose + ATP –> G-6-P + ADP?57
[3] Reactions that are spontaneous are generally exergonic. In the individual and coupled reactions in the review question [2],
which reaction is exergonic, which is endergonic?58
Overall, is catabolism exergonic or endergonic; is anabolism exergonic
or endergonic?59
ENZYMOLOGY
14. Which term of the Michaelis-Menten equation,
[ ]
[ ]SK
SV
v
m +
= max
can be determined from the x-intercept of a Lineweaver-Burke plot?
A. v
B. Vmax
* C. Km
D. [S]
[1] What is a double reciprocal plot, and why is it advantageous in determining Km and Vmax?60
[2] What is the meaning of Km and Vmax for an enzyme reaction?61

[3] Why is the initial velocity (vo) important for determining v of an enzyme reaction; what are zero and first order kinetics,
relative the Km?62
CATABOLISM
15. All the following reactions occur during glycolysis EXCEPT ONE. Which is reaction is the EXCEPTION?
A. fructose-6P + ATP (phosphofructokinase–1)  fructose-1,6-BP
* B. fructose-2,6-BP (aldolase)  2 glyceraldehyde-3P
C. glyceraldehyde-3P + NAD+
(G3P dehydrogenase)  1,3-bisphosphoglycerate + NADH
D. 1,3-bisphosphoglycerate + ADP (phosphoglycerate kinase, PK)  3-phosphoglycerate + ATP
E. pyruvate + NADH (lactate dehydrogenase)  lactate + NAD+
Related study questions and perspectives on glycolysis
[1] What is the purpose of glycolysis63
; why is reaction ‘A’ the committed step?64
What is the major product of aerobic versus
anaerobic glycolysis?65
[2] The red blood cell (RBC,) like all cells, contains only trace quantities of coenzymes (hence “catalytic quantities”). The
RBC would convert the tiny supply of NAD+
to NADH very quickly and then glycolysis would stop! Which listed enzyme
reaction ‘?’ prevents this metabolic collapse?66
[3] Reactions C and D constitute a catalytic process known as substrate level oxidative phosphorylation, which is one of two
substrate level means of ATP regeneration (from ADP) essential for sustaining all ATP-dependent RBC metabolic
reactions from collapse. Ironically complete reliance on C and D produces a lower net ATP yield compared to all other
cells. What cellular organelle is uniquely missing in the RBC that other cells have and rely upon extensively for most ATP
regeneration and thereby bypass cytosolic lactate dehydrogenase to regenerate their NAD+
?67
[4] Which highly exergonic enzyme reaction (not listed, which in contrast to D doesn’t need an oxidative reaction like C),
provides the second substrate level phosphorylation of ADP in the RBC (all other glycolytic cells too)?68
[5] In other cells, which have mitochondria and can funnel NADH into both cytosolic lactate dehydrogenase or the
mitochondrial respiratory chain (in proportion to dynamic hypoxic oxygen levels), the net ATP regeneration ratio goes up
or down between the extremes of 2 and 8 ATP per glucose oxidized. What is the name given to glycolysis at either
extreme?69
[6] With the above in mind, can you appreciate why the glycolytic throughput must end in lactate not pyruvate? Hence, the
major source of plasma lactate is understood?70
What other major tissue can produce and secrete massive quantities of
lactate into the plasma using glycolysis?71
16. Which of the following glycolytic liver enzymes is NOT product-inhibited and is absent in muscle cells?
A. Hexokinase
B. Enolase
C. Aldolase
* D. Glucokinase
E. Glucose-6-phosphatase
[1] After a meal, glucose uptake in liver cells is facilitated and rapid compared to muscle cells because liver has an additional
glucose kinase that is not product-inhibited and has a higher Km for glucose. Why are these distinctions important for
appreciating special liver cell functions compared to muscle cell function?72
[2] An abrupt and sustained increase in diet glucose induces gene expression of one of these liver kinases, which enzyme is
inducible and why is that advantageous for liver functions?73
ANABOLISM
17. Select the statement about glycogen biochemistry that is INCORRECT.
A. Glycogen is composed of highly branched chains of α−glucose residues.
B. Glycogen’s outward branching provides reactive ends for extremely rapid incorporation and release of glucose.
C. Glucose residues are linked by acetal α(1  4) bonds.
D. Approximately 1 in 8 glucose residues are linked by an acetal α(1  6) bond.
* E. Glycogen is hydrophilic and therefore is less dense than triacylglycerides.
[1] What special aspects of acetal linkage properties and associated enzymes are advantageous with respect to storage of glucose
in starch and glycogen or for use of glucose for structural strength characteristic of cellulose?74

[2] Explain how the highly branched polymer structure of glycogen provides a major advantage compared to the structure of the
linear starch polymer in facilitating different in rates of synthesis and breakdown (i.e., storage and release) for both
polymers?75
[3] Is this consistent with muscle using glycogen rather than starch, which is used in plants?76
18. Unlike β-oxidation of fatty acids, fatty acid synthesis requires only:
A. NAD+
* B. NADPH
C. FAD
D. FADH2
[1] In the fatty acid synthesis pathway, which two reactions use NADPH; in contrast, which of the listed redox coenzymes are
used in the β-oxidation catabolic pathway?77
[2] Which metabolic pathway(s) or reaction(s) supply NADPH for FA synthesis; which vitamin, if deficient, therefore interferes
with FA synthesis, which second vitamin, if deficient with the first interferes with both FA pathways?78
[3] Which inherited enzyme deficiency was first revealed when an antimalarial (primaquine) was prescribed that lead to
insufficient NADPH production in the hexose monophosphate shunt in RBCs that developed into hemolytic anemia?79
REGULATION
19. Regulation of glycolytic enzyme activity includes posttranscriptional phosphorylation/dephosphorylation of:
* A. pyruvate kinase
B. glycogen synthase
C. phosphorylase kinase
D. phosphorylase a
E. phosphofructokinase-1
[1] A variety of regulatory mechanisms control the flux of molecules through the glycolytic pathway. These include substrate
availability, inhibition, allosterism, and posttranslational modification. Which enzymes are regulated by these mechanisms?80
[2] Which small glycolytic molecules, including those from other pathways, are involved in the regulatory mechanisms of
glycolysis?81
[3] Which pancreatic hormone(s) stimulates or inhibits glycolytic activity?82
By what mechanisms?83
20. Which key substrate of fatty acid synthesis also controls the inhibition of β-oxidation and thereby prevents a futile
cycle?
A. acetyl CoA
* B. malonyl CoA
C. citrate
D. pyruvate
E. propionyl CoA
[1] What is a futile cycle; why would metabolic futile cycles be life threatening?84
[2] What is the activated substrate for cytosolic fatty acid synthesis; which molecule inhibits the enzyme-driven entry of acyl
CoA fatty acids into the mitochondria for β-oxidation?85
How do those properties prevent a futile cycle in fatty acid
metabolism?86
[3] Excess dietary glucose is easily converted to fat and stored. Oddly enough, acetyl CoA arises from pyruvate via cytoplasmic
glycolysis of the excess glucose. Why does acetyl CoA become trapped inside the mitochondrion after mitochondrial
pyruvate dehydrogenase acts on pyruvate?87
[4] How does acetyl CoA escape the mitochondrion88
; how does acetyl CoA (and OAA) arise from cytosolic citrate89
; how is
acetyl CoA activated with CO2 to form malonyl CoA.90
[5] How does propionyl CoA arise from β-oxidation of odd-numbered fatty acids?91
INTERDISCIPLINARY CLINICAL/CROSS CORRELATION
21. Nucleoside derivatives are effective antibiotics compared to their free bases because after phosphorylation to
nucleoside triphosphates, the appropriate cellular polymerases then incorporate them into
A. the primary sequence of full length histone nucleoproteins in bacteria interfering with transfection.

B. polysaccharides that unfold DNA supercoils interfering with chromosome replication.
C. the 5'terminal cap of hnRNA pre-mRNA interfering with posttranscriptional processing.
* D. RNA or DNA transcripts either for subsequent inhibitory effects or termination of further polymerization.
[1] What is azido thymidine, dideoxyadenosine, and puromycin; what structural features make each of these nucleosides
effective antibiotics due to their mode of action?92
[2] Which cellular enzymes interconvert nucleosides and nucleotides, exchange sugars of nucleosides, salvage purine and
pyrimidine bases directly to nucleotides thereby allowing nucleotides and their drug analogs metabolic effectiveness?93
[3] Cite at least one example of a nucleoside with a modified sugar that terminates DNA synthesis thereby inhibiting
productive infection by the AIDS virus?94
22. An immigrant migrant farm worker presents her 5-year old male child to the emergency room complaining “All his
teeth are rotting, he cries all the time and seems to be in pain.” Examination reveals that the boy is unable to understand
and answer simple questions and has an unusual gait, sitting posture, and very light pigmentation. The family history
indicates male mental retardation and epilepsy, but otherwise normal dental histories. Urine analysis indicates excessive
phenylpyruvate, phenyllactate and a mousey smell. Further tests confirm phenylalanine hydroxylase deficiency. The most
likely diagnosis is:
A. Albinism.
B. Alkaptonuria.
C. Maple syrup urine disease (MSUD).
* D. Phenylketonuria.
[1] What simple test detects phenylketonuria (PKU) shortly after childbirth because it is mandated by law in most states, but
often is not performed in foreign countries? Which aspect of metabolism is affected?95
[2] What adjustment is made to the dietary formula to prevent mental retardation from developing in the infant?96
[3] Explain why a patient with PKU is on the horns of a dilemma in trying to balance a possible essential amino acid deficiency
against neurotoxicity of phenylalanine?97
[4] Why is rampant caries and very light pigmentation both irrelevant for the diagnosis of this case?98
[5] Why can a tyrosine supplement compensate for occasional unintended phenylalanine dietary excess?99
23. Jaundice in a patient with a history of alcoholic cirrhosis is most likely due to a metabolic dysfunction in:
A. bilirubin synthesis by the liver.
* B. bilirubin catabolism by the liver.
C. cytochrome synthesis by the pancreas.
D. cytochrome catabolism by the pancreas.
[1] What is the pathway of heme synthesis and catabolism?100
[2] Where do each of these synthetic and catabolic reactions occur?101
[3] What are jaundice and hepatomegaly?102
24. All of the following correctly complete the sentence about sickle-cell anemia EXCEPT ONE. Which is the EXCEPTION?
“Sickle cell anemia was the first complex disease discovered to be due to …
A. a single nucleotide mutation in the gene coding for β-hemoglobin A.”
* B. a nonsense codon mutation in the gene coding for β-hemoglobin A.”
C. an altered hemoglobin conformation that promotes insoluble fibril formation.”
D. distorted cell shape and cell inflexibility that leads to blocked capillaries and localized micro hypoxia. ”
E. a variety of clinical signs and symptoms. ”
[1] What is the nature of the mutation in sickle cell anemia?103
[2] What causes the change in shape and flexibility during hypoxia?104
[3] Why does sickle cell anemia show a variety of clinical signs and symptoms?105
25. All of the following are true statements concerning zymogen activation cascades EXCEPT ONE. Which is the
EXCEPTION? Zymogens:
A. are often triggered in emergency situations when rapid response is essential.
B. provide very rapid amplification of active enzyme catalysis.
C. avoid life-threatening circumstances by accelerating enzymological responses.

D. provide a mechanism for rapid serial feedforward catalytic activations within a response pathway.
* E. provide critical cCMP hydrolysis activations for rapid signal transduction mechanisms.
[1] What is a zymogen?106
[2] Why do we need zymogen cascades?107
[3] Which body systems require zymogen cascades?108
MOLECULAR BIOLOGY (8)
DNA/RNA AND PROTEIN SYNTHESIS
26. All of the listed proteins EXCEPT ONE contains an N-terminal signal peptide that is bound by the Signal Recognition
Particle (SRP) and is subsequently cleaved as a posttranslational modification. Which nascent protein lacks the signal
peptide and is not exported by the cell?
A. Collagen
B. Fibrinogen
* C. Tubulin
D. Immunoglobin
E. Fibronectin
[1] What is unique about the amino acid sequence of the signal peptide and where in the polypeptide chain is it located?109
[2] How does the signal peptide differentiate ribosomes synthesizing collagen, fibrinogen, plasma fibronectin, and immunoglobin
polypeptide chains for excretion from other ribosomes synthesizing proteins that will remain inside a fibroblast, liver, or
immune cell?110
Define intracellular versus an extracellular protein, and endogenous versus exogenous proteins from those
listed?111
[3] What is the cytoplasmic SRP complex that sorts proteins for secretion or retention based upon the signal peptide?112
[4] Why do ribosomes dock to the endoplasmic reticulum; what is the fate of the signal peptide; what is the fate of the remaining
–COOH end of the newly synthesized polypeptide; what organelle(s) may perform additional posttranslational
modifications?113
27. The TATA box is important for initiation of which process?
A. mRNA capping
B. DNA replication and
* C. RNA transcription
D. RNA translation
E. HnRNA splicing
[1] What is a nucleic acid consensus sequence, where are they located and what type of proteins interact with them?114
[2] What is the role of the TATA box in a promoter, do all genes have this sequence, if not, cite an example?115
[3] What consensus sequences are involved in mRNA synthesis, processing, and translation?116
[4] What role does capping and polyadenylation play in eukaryotic mRNA maturation and translation?117
28. Which statement is INCORRECT about the typical purine-rich, AGGAGG consensus sequence in bacteria and
bacteriophages?
A. It is approximately 10 nucleotides upstream from the initiator AUG codon.
* B. It is usually capped with m7
GpppG.
C. It ensures appropriate polycistronic translation.
D. It binds near the 3’ terminus of 16S ribosomal RNA.
E. It is called the Shine-Dalgarno in mRNA.
[1] Compare structures of prokaryotic mRNA and eukaryotic mRNA that are involved in the initiation phase of protein
synthesis?118
[2] How does the Shine-Dalgarno sequence align the ribosome with the AUG start codon?119
In polycistronic prokaryotic mRNA,
how does the Shine-Dalgarno ensure all cistrons of bacterial mRNA are translated?120
[3] Why would coordinated multi-protein expression fail in polycistronic mRNA without the purine-rich Shine-Dalgarno
sequence?121
29. The m7
GpppN cap is a posttranscriptional modification of eukaryotic:

A. DNA introns
B. histones
C. tRNA
* D. hnRNA
E. rRNA
[1] What aspect of the Central Dogma (Watson and Crick, 1953) does the question address?122
[2] What is a posttranscriptional modification; which modifications occur during and which after transcription is complete?123
[3] Which structural modification requires, GTP and S-adenosyl methionine (SAM); which need only SAM?124
[4] Which initiation factor binds recognizes the +1 charge in the 5’-m7
GpppN cap of eukaryotic mRNA that facilitates
translation?125
[5] Which three metabolic coenzymes have a structural feature similar to the mRNA cap?126
30. A sample of DNA from a patient’s amniotic fluid cells is prepared for DNA fingerprinting by treatment with an
enzyme that will hydrolyze specific phosphodiester bonds of both strands within the sequence, 5’–GAATTC –. Which
type of enzyme is used?
A. topoisomerase
* B. restriction endonuclease
C. ligase
D. exonuclease
E. polymerase
[1] What substrates do restriction enzymes, topoisomerases, ligases, exo- and endonucleases, and polymerases act on?127
[2] What role does each listed enzyme perform in a bacterial cell, in a human cell;128
how does the cell distinguish its DNA from
foreign DNA in order to abort the biological threat of the foreign DNA?129
[3] What is a DNA fingerprint; what applications does it have in medicine?130
GENETIC ENGINEERING
31. By 1975, the cloning of dsDNA fragments became possible after which pair of enzymes were discovered?
* A. DNA restriction enzyme and DNA ligase
B. DNA restriction enzyme and polynucleotide phosphorylase
C. DNA endonuclease I and DNA ligase
D. DNA polymerase I (Kornberg) and DNA ligase
E. Topoisomerase I and DNA ligase
[1] What is the substrate specificity of hydrolytic DNA restriction enzymes; why must a cell methylate its DNA if it expresses a
restriction enzyme?131
What are blunt ends compared to cohesive or “sticky” ends produced by restriction enzymes?132
[2] What does DNA ligation accomplish; why are DNA-ligases NAD- or ATP-dependent? Why do DNA ligases yield stable
recombinant DNA molecules suitable for molecular cloning
[3] What aspect of the polymerase reaction do DNA ligases mimic, but also lack that prevents them from being a DNA
polymerase?133
[4] What is similar/dissimilar about DNA topoisomerases and ligases?134
[5] Compare RNA polymerase to polynucleotide phosphorylase (PNP) discovered in 1955, in the bacterium A. vinelandii?135
32. Why are plasmids used for molecular cloning of DNA designed with two antibiotic resistance genes?
A. Double resistance ensures replication and resistance of host cell to the recombinant.
B. Double resistance boosts plasmid copy number and replication efficiency in the host cell.
* C. Double verification that recombination occurred and that the host cell was successfully transfected.
D. Double verification that recombinant plasmid can kill transfected cells, leaving uninfected cells for cloning.
[1] What is a plasmid, transfection, plasmid copy number, an antibiotic resistance gene?136
What is the connection between
ampicillin, tetracycline, and plasmids?137
[2] DNA inserted into a gene for drug resistance abolishes the drug resistance for the cell. Does the loss of drug resistance verify
that the DNA insertion was successful?138
[3] What is the rationale for putting two antibiotic resistance genes into a plasmid such that one gene contains a restriction site?139
INTERDISCIPLINARY CLINICAL/CROSS CORRELATION

33. A newly arrived short, 50-year-old female visiting from a remote region of Central America weighs 250 lbs and
presents to an oral surgery clinic. She is referred to the hospital’s diabetes clinic. In spite of daily insulin (porcine)
injections for 4 months, her glycosylated HbA1c is 14% (normal 6%), and she has a high titer of antibodies to insulin.
The clinic physician will most likely conclude that:
A. she must be put on a low carbohydrate diet immediately.
B. her carbohydrate metabolism was not controlled for the last 3-months.
C. her immune response to porcine insulin has made her hyperglycemic.
D. she must be put on cloned human insulin to bypass the immunity to the porcine insulin.
* E. all of the above.
[1] Why is glycosylation of HbA1c of 9-12% indicative of hyperglycemia and poor management of dietary glucose?140
[2] Explain why diabetes is referred to as “starvation in the presence of plenty.”141
[3] Explain how type 1 and 2 diabetes mellitus are similar and dissimilar?142
[4] Why is use of animal insulin for treatment of diabetic patients problematical whereas human insulin is not?143
[5] Why is molecularly cloned human insulin preferred for treatment of diabetes?144
34. Which of the following antibiotics would most likely be administered to treat an oral cancer by specifically inhibiting
the complex enzyme reaction: dUMP  dTMP?
A. Actinomycin D
* B. Methotrexate
C. Puromycin
D. Tetracycline
E. Trimethoprim
[1] What metabolic enzyme or process does each of the listed antibiotics inhibit?145
[2] What is methotrexate; what other drugs resemble methotrexate and are folate antagonists? Why must the patient be injected
with tetrahydrofolate within 15 minutes after administration?146
[3] What biochemical process(es) do Actinomycin D, puromycin, tetracycline, and trimethoprim inhibit?147
[4] Which bodily cells would be most affected by methotrexate, in addition to the cancer cells?148
[5] Which of the listed antibiotics are effective in prokaryotes, which are effective in eukaryotes?149
NUTRITIION
NUTRIENTS/MINERALS
35. Which of the following B-complex vitamins should NOT be administered to correct the respective deficiency disease?
A. B1 thiamine : beriberi
* B. B2 riboflavin : megaloblastic anemia
B. B3 niacin : pellagra
C. B6 pyridoxine : neurologic disease
D. B12 cobalamin : pernicious anemia
[1] Of the listed vitamins, which is a coenzyme, which is inactive until combined with other molecule(s)?150
[2] Which vitamin(s) is involved in oxidation-reduction reactions; in 1-carbon transfers, in 2-carbon transfers?151
[3] Which are water soluble vitamins, which are fat soluble vitamins?152
[4] What is at least one major characteristic of each deficiency disease?153
36. Dietary deficiency of vitamin B6 significantly affects the metabolism of:
* A. amino acids by decreasing transamination reactions.
B. nucleic acids by increasing synthesis.
C. fatty acids by decreasing their activation.
D. carbohydrates by increasing glucosamine synthesis.
[1] Of the three forms: pyridoxine, pyridoxal, and pyridoxamine, which is the major form of B6 in the diet, which is the active
form of the vitamin, and which form of B6 or corresponding phosphates are water or lipid soluble?154
[2] Which form is usually involved in a Schiff base intermediate that can yield an amination/deamination, decarboxylation, or
dehydration reaction?155

[3] What enzyme reaction, using B6 as cofactor, is the first step in the synthesis, catabolism, and interconversion of amino
acids?156
37. Which of the following metabolic processes/compounds would be negatively affected in copper and iron deficiency
anemia?
* A. oxidative phosphorylation, oxygen transport, and myoglobin
B. glycolysis, glycogenesis, and respiratory cytochromes/nonheme FeS
C. lipogenesis, ketogenesis, and transferrin
D. oxidative phosphorylation, tricarboxylic acid cycle, and ceruloplasmin
[1] What trace metal nutrients are essential for respiratory transport chain enzymes, adequate hematocrit for oxygen transport, and
myoglobin retention of oxygen in muscle?157
[2] Although a muscle protein for iron storage, the traces of serum ferritin level is 99% specific for which anemia?158
[3] Which plasma copper-carrying protein scavenges superoxide and other oxygen free radicals that damage plasma proteins
(including hemoglobin) and is defective in Wilson’s disease?159
[4] What effect does copper deficiency anemia have on iron transport, on methemoglobin level and on the synthesis of two
important connective tissue proteins; what kinds of anemia are associated with copper and iron deficiencies?160
REQUIREMENTS
38. Inadequate dietary intake of essential amino acids can lead to metabolic disturbances such as:
* A. negative nitrogen balance
B. positive nitrogen balance
C. excessive protein synthesis
D. increased blood volume
E. increased lipogenesis and glycogenesis
[1] Why are eight of the 20 amino acids incorporated into proteins essential or indispensable to the body; identify them?161
[2] What is nitrogen balance; why does protein metabolism account for most biochemically usable nitrogen in the body?162
[3] What is the best source of protein for humans, i.e., has optimal amino acid ratios, complete digestibility, absorption, and
utilization?163
[4] If dietary methionine suddenly drops to 50% of the minimal recommended daily allowance (RDA), why does protein
synthesis in all tissues decrease by approximately the same percentage until methionine intake increases to the RDA?164
[5] During essential amino acid deficiency, why does the body begin to lose essential nitrogen from its amino acids and
proteins?165
FUNCTIONS
39. Two key enzymes, dTMP synthase and deoxyribonucleoside diphosphate reductase, are involved in synthesis of
deoxyribonucleotides from their corresponding ribonucleotides. Which coenzyme listed below is neither the reactant nor
product form of the coenzymes involved in those reactions?
A. N5,10
-methylene tetrahydrofolate
B. dihydrofolate
C. NADPH
* D. NADH2
[1] In humans, all DNA nucleotides are synthesized from their RNA counterparts via two key enzyme reactions, one reduces
ribose to deoxyribose, the other methylates uracil to thymine, outline both reactions.166
[2] For the conversion of dUMP to dTMP, outline the two essential ancillary reactions that keep it going.167
[3] Both ancillary reactions utilize coenzymes that are vitamin-dependent. Which vitamins are they?168
[4] Conversion of ribose to deoxyribose involves a hydride transfer. What is a hydride; which vitamin component of the
coenzyme involved transfers the hydride to C2
of ribose?169
[5] dTMP synthesis involves a 1-carbon fragment transfer using folate. What are the two other carriers of 1-carbon fragments
found in metabolism, both of which participate in nucleic acid syntheses?170
40. Which of the following is INCORRECT about zinc?
A. Zinc is involved in carbohydrate and energy metabolism.
B Zinc is involved in synthesis of metallothioneine, which binds Zn for its absorption in the gut.
* C. Zinc is a divalent heavy metal that is as toxic as lead.

D. Zinc, in increased oral doses, interferes with copper absorption and deficiency.
E. Zinc deficiency affects growth, impairs of taste and smell, and delays wound healing.
[1] Which carbohydrate metabolism enzymes require zinc, i.e., their holoenzyme is an active zinc metalloenzyme, but their
nonmetalloenzyme apoenzyme is inactive?171
[2] What is metallothioneine protein, where is it synthesized, and what is its role in trace metal absorption?172
[3] What is the connection of Wilson’s disease to copper and zinc metabolism and likely effect on enzymes requiring them?173
INTERDISCIPLINARY AND CLINICAL/CROSS CORRELATION
41. Which vitamin is INCORRECTLY paired with the consequence(s) of its deficiency?
A. vitamin D : rickets
B. vitamin C : scurvy
C. niacin : dermatitis, diarrhea and dementia
* D. thiamine : polycythemia
E. folate : anemia
[1] Of the vitamins listed, which tissue(s) is usually affected; what signs and symptoms are observed by clinicians during
examination of patients with the listed deficiency diseases; what deficiency disease corrects the INCORRECT answer pair?174
[2] Which of the vitamins listed are water soluble; which are lipid soluble?175
[3] What foods are usually recommended to restore health, if that is possible?176
42. A dentist recommends postponement of oral surgery upon learning the patient has leukemia and is scheduled for
folate antagonist (methotrexate) treatment in two days. The postponement recognizes the complications of anti-
folate biochemistry and its effects on post operative tissue healing. Which is INCORRECT about folate antagonists?
They…
A. indirectly block the synthesis of dTMP from dUMP by thymidylate synthase.
B. inhibit dihydrofolate reductase.
C. mimic the isoalloxazine ring of tetrahydrofolate.
* D. block hydride transfer by nucleoside diphosphate reductase.
E. treat blood leukemia disorders.
[1] Why does methotrexate indirectly inhibit the thymidylate synthase and also indirectly inhibit all other tetrahydrofolate-
dependent metabolism?177
[2] What glucose pathway supplies NADPH required to regenerate dihydrofolate (FH2) to tetrahydrofolate (FH4)?178
[3] A part of DNA synthesis is serine-dependent. What part of serine’s structure supplies the 1-carbon fragment subsequently
added to N5
in the isoalloxazine ring of folate?179
[4] N5
,N10
-methylene tetrahydrofolate is converted to what folate form by thymidylate synthase that has no other metabolic
utility, i.e., is a dead-end metabolite?180
CONNECTIVE TISSUES
SOFT TISSUE
43. Identify the INCORRECT statement about collagen: “Collagen is an important component of extracellular matrix
(EMC) in connective tissues because the … ”
A. repeated Gly-X-Y tripeptide in all three subunit chains permits the required tertiary and quaternary structure
for collagen’s structural role.”
B. tertiary structure of each of the triple strands coils into a left-handed, α-helical conformation.”
C. triple-stranded, cross-linked, right-handed super helical quaternary structure forms strong, stable, rigid, rod-like
molecules that aggregate into fibrils.”
D. hydroxyproline on the surface can be linked to various carbohydrates. “
* E. triple stranded subunits are also stabilized by a cluster of cystine cross links.”
Related study questions 8888 Endnotes editing stops here 8888
[1] What is extracellular matrix; why is it needed in connective tissue?181
[2] What are the chemical features of collagen’s repeated tripeptide Gly-X-Y that are responsible for collagen’s unique 2º, 3º, 4º
structures and role in connective tissue?182

[3] What intermolecular arrangement accounts for the banded appearance of fibrillar collagen?183
HARD TISSUE
44. Hyaluronic acid, heparin, and chondroitin-, dermatan-, heparin-, and keratin-sulfates are found in:
A. anticoagulants
* B. proteoglycans
C. hormones
D. fibronectins
E. simple lipoproteins
[1] What are simple- and derived-sugars; which are found in complex carbohydrates? Which sugar is in RNA versus DNA?184
[2] What are the different chemical forms of glycoconjugates; which are classified as glycolipids?185
[3] Which functional groups are added to glucose, galactose, mannose, glucuronic acid, etc., that give rise to the carbohydrates
and their molecular categories listed in the question.186
45. Which property about enamel is INCORRECT in comparison to other mineralized tissues within the body?
A. Enamel is the hardest.
B. Enamel contains mostly hydroxyapatite.
* C. Enamel contains amelogenin proteins.
D. Enamel contains hexagonal rod crystals that are larger and more firmly packed.
[1] What are the seven systems that all crystalline minerals are categorized into; calcium phosphate (empirical formula:
Ca10(PO4)6(OH)2) a member of which system? What is its common mineral name?187
[2] Is this mineral harder than calcium phosphate mineral found in bone? What scale is used to determine/classify mineral
hardness?188
[3] What are amelogenins and where are they found in hard tissue? What features make them suited for their role in
mineralization?189
[4] Which calcium phosphate exchanges a fluoride ion for a hydroxyl ion, and what property is enhanced by fluoride?190
MEMBRANES
STRUCTURE
46. Which of the following compounds are bonded to phosphate in diacyl phosphoglycerol to complete the repertoire of
phospholipids found in body membranes?
A. Only choline
B. Betaine and sphingosine
C. Choline, betaine, and sphingosine
D. Choline, serine, and sphingosine
* E. Choline, serine, ethanolamine, inositol
[1] What are diacylphosphoglycerol, phosphatidyl choline, phosphotidyl serine, phosphatidyl ethanolamine, and phosphatidyl
inositol?191
[2] Which amino acid is converted to ethanolamine, choline, and betaine; which sulfur-containing amino acid is salvaged in
which betaine is involved?192
[3] What function(s) do phosphatidyl lipids serve in the membranes or the cytosol?193
NERVOUS SYSTEM
GENERAL PROPERTIES
47. The enzyme UNIQUE to nerve tissue is:
* A. glutamate decarboxylase
B. ornithine decarboxylase
C. tryptophan decarboxylase
D. glycine decarboxylase
E. aspartate decarboxylase
[1] Which amino acid metabolism enzyme listed is tissue-specific for nerve tissue?194
[2] What is the amino acid product of each listed enzyme and what vitamin/coenzyme is involved?195
[3] GABA is an abbreviation for what amine derived from glutamate?196

[4] Where is GABA synthesized and stored and what is GABA used for?197
MUSCLE
SKELETAL
48. Which comparison between hemoglobin and myoglobin of skeletal muscle is INCORRECT?
A. Myoglobin is more oxygen saturated at lower PO2 levels than hemoglobin.
B. Both are inside cells.
C. Both contain Fe2+
combined with porphyrin.
* D. Each molecule is composed of different subunit proteins.
E. Hemoglobin transports oxygen while myoglobin stores oxygen.
[1] What are myoglobin and hemoglobin, what tissues contain them, what are their functions?198
[2] What is the porphyrin family; where are they synthesized?199
[3] What divalent metal cation does porphyrin bind in humans and what common name is given to the metalloporphyrin?200
[4] What is the significance of the myoglobin O2 saturation curve being hyperbolic but hemoglobin’s is sigmoidal?201
CIRCULATION
COAGULATION
49. The coenzyme for γ−carboxylation of glutamyl residues required for synthesis of Ca2+
chelation clusters near the N-
terminus of zymogens II, IX, X, and IX contains which vitamin?
A. pantothenic acid
B. B1
* C. K
D. lipoic acid
E. biotin
[1] What chemical properties does the γ-carboxyglutamyl side-chain have that enables it to act as a divalent metal cation
chelation group?202
[2] What function results from the cluster of γ-glutamates near the N-terminus of specific coagulation zymogens? Why those
four factors and not some of the others?203
[3] When trauma disrupts endothelial cells lining blood vessels thereby exposing phospholipids, factors, II, IX, X, and XI
concentrate on the phospholipids exposed at the trauma site; what enzymological principles and effects on reaction rates
are demonstrated?204
[4] What role(s) does γ-carboxyglutamyl residues in bone osteocalcin suggest for a role(s) of vitamin K in osteoporosis?205
[5] Can you think of an example of carboxylations that are on the α−, β−, δ−, and ε−carbons of other metabolites? Which of
these might act as chelators?206
RESPIRATION
GAS EXCHANGE AND TRANSPORT
50. All of the following are true for oxygen carriage biochemistry EXCEPT one. Which is the EXCEPTION ?
A. Binding of 2,3–bisphosphoglycerate to hemoglobin lowers O2 affinity for hemoglobin in capillaries.
B. Association of H+
to hemoglobin decreases its affinity for oxygen.
C. CO2 is a negative allosteric effector that promotes O2 dissociation from HbO2 when it forms
carbaminohemoglobin.
* D. Deoxyhemoglobin (reduced) has a lower pKa than oxyhemoglobin.
[1] What pathway in the red blood cell does 2,3-BPG arise from; how does the nearly molar equivalent ratio of 2,3-BPG:
deoxyhemoglobin chains affect O2 binding?207
[2] Which has a greater affinity for H+
: deoxyHb or HbO2?208
[3] Explain Bohr’s observation that increasing the CO2 in blood released oxygen from it. What other molecule is involved?209
[3] Where on the β-globin chain of Hb does CO2 react to form carbamino Hb; how much CO2 is transported as CO2, as HCO3
–
,
as carbamino Hb in RBC, in plasma?210
EOF:gcl

National Board Part I Examination Specifications (2002)
Building Blocks of Life Course (41)
I. Physical-Chemical Principles (3)
A. Basic principles (2)
B. Applied principles (1)
II. Biological Compounds (9)
A. Sugars and carbohydrates (1)
B. Amino Acids and proteins (2 )
C. Lipids (1)
D. Nucleic Acids and metabolism (1)
E. Interdisciplinary clinical/cross correlation (4)
III. Metabolism (13)
A. Bioenergetics (1)
B. Enzymology (1)
C. Catabolism (2)
D. Anabolism (2)
E. Regulation (2)
F. Interdisciplinary clinical/cross correlation (5)
---25 ---
IV. Molecular Biology (8)
A. DNA/RNA and protein synthesis (4 )
B. Genetic engineering (2)
XIV. Nutrition (8)
A. Nutrients/minerals (3)
1. Requirements (1)
2. Functions (2)
B. Interdisciplinary and clinical/cross correlation (2)
---16 of 25 ---
---9 of 25 ---
V. Connective Tissues (8) (in Basic Tissues)
A. Soft tissue (2)
B. Hard Tissue/calcification (3)
C. Interdisciplinary and clinical/cross correlation (3)
VI. Membranes (4) (most in Cell Organelles )
A. Structure (1)
B. Function (1)
VII. Nervous System (9) (most in Organ Systems)
A. General properties (2)
B. Central nervous system (1)
C. Autonomic nervous system (1)
D. Somatic nervous system (with reflexes) (2)
E. Special senses (1)
VIII. Muscle (6) ()
A. Skeletal (2) metabolism and myoglobin
B. Smooth (1)
C. Cardiac (1)
IX. Circulation (9) (in Basic Tissues/clotting/gas transport
A. Fluid content and dynamics (2)

B. Coagulation (1)
C. Cardiodynamics and electrophysiology (2)
C. Regulation (1)
X. Respiration (6) (in Basic Tissues)
A. Mechanical aspects (1)
B. Gas exchange and transport (1)
C. Regulation (1)
XI. Renal (6) (see Organ Systems)
A. Functional anatomy (1)
B. Blood flow and filtration (1)
C. Reabsorption and secretion (1) metabolites
XII. Acid-Base Balance (1) (in Organ Systems)
XIII. Digestion (5) (in Organ Systems)
A. Neuromuscular (1)
B. Secretions (1) enzymes
C. Absorption (1)
D. Regulation (1)
E. Interdisciplinary and clinical/cross correlation (1)
XV. Endocrines (8) (in Organ Systems)
A. Pituitary/hypothalamus (1)
B. Reproduction (1)
C. Signaling systems (2) insulin/glucagon & cAMP
D. Pancreas/parathyroid (1)
E. Adrenal/thyroid (1)
END NOTES – Answers to Related Study Questions

1
The Biochemistry-Physiology Part I National Boards Examination covers 15 topic areas with 80 subtopics in 100
questions listed below divided into the Topics covered by Building Blocks of Life and other D1 basic science
courses.
2
Plasma pH 7.45, although stomach (3.5), duodenum (8.0), etc may differ.
3
The strength of an acid is determined by (a) the strength of its conjugate base, (b) the basic strength of the solvent,
and (c) the dielectric constant of the oppositely charged particles dissolved in them, which necessarily favors
dissociation. In aqueous solution, strong acids completely ionize (e.g., HCl, because HOH, water is a weak acid),
whereas weak acids (acetic acid in water) ionize to the extent of the density of negative charge on the conjugate base
(CH3COO–
). Iodoacetic acid is stronger than acetic acid because iodine on C2
inductively weakens the acid bond and
decreases the carboxylate anion negative charge density, hence, protons dissociate more easily and are less attracted
to the weaker iodocarboxylate anion (ICH3COO–
). compared to the acetate ion. This phenomenon is called the
neighboring group effect. Substitution of an amino group on C2
(instead of Iodine) yields glycine, the –NH3
+
thereby
inductively makes the –COOH a stronger acid than the –COOH of acetic acid so the pKa of former is lower than
acetic acid’s.
4
Of those listed, only D. –COOH, carboxylic acid group is dissociated at pH 7.5. A. CH2 methylene hydrogens, B.
C–OH alcohol group, C. –NH3
+
ammonium, E. phenol all are not dissociated at pH 7.5 to any significant degree,
which is what the question asked. However, strong electron withdrawing, neighboring groups (e.g., in malonyl CoA)
may lower the pKa sufficiently close to pH 7.5, for the –CH2– middle methylene to be significantly ionized –
OOC–
CH2–CO-CoA yielding a carbanion –
OOC–CH(–)
–CO-CoA.
5
In the ionized zwitterion (–/+)of an amino acid, the protonated –NH3
+
ammonium group strongly attracts electron
density from the ionized –COO–
anion making it a weaker conjugate base (less electron dense), hence the proton
dissociates more readily then an isolated carboxylate anion (e.g., as in acetate). Conversely, the electron density
available on the –COO–
can be donated to the electron deficient (positively charged) amino group thereby lessening
its electron deficiency. The mutual neighboring group effects shift the pKa of each group by about 1-2 pH unit.
6
Two, analogous to a pair of left and right hands.
7
Using Fischer representation, when several asymmetric carbon (C*) atoms are in a chain molecule, and the end
groups are not identical and not asymmetric, the remaining number of stereoisomers possible is equal to 2(exp n), or
2n
, where n is the number of asymmetric carbon atoms. When linear sugars cyclize, an additional C* is formed
(because the C1
aldehyde reacts with the internal alcohol (to form an intramolecular cyclic or internal hemiacetal,
which is a new asymmetric center). [Note: a hemiacetal can condense with a second mole of alcohol to form an
acetal, e.g., D-glucose + methanol  methyl–α− and –β−D–glucoside, same number of isomers are possible.]
8
For linear aldopentoses: 2(3)
= 8; for aldohexoses: 2(4)
= 16.
For ring-closed (Haworth projection) pentoses: 2(4)
= 16, for hexoses: 2(5)
= 32.
9
For linear ketohexoses: 2(3)
= 8. [C2
ketone the internal keto group and two non identical end groups leave only 3 C*.
For closed-ring hexose: 2(4)
= 16. [C2
ketone adds an alcohol to form an intramolecular cyclic or internal hemiketal,
which is asymmetric (can form 6- and 5-membered rings). [Note: a hemiketal condenses with an alcohol to form a
ketal, e.g., D-fructose + methanol –> methyl–α− and –β−D–fructoside, same number of isomers possible.]
10
C1
is the anomeric carbon of aldose sugars. Hemiacetal formation creates a new C* center, thus two anomers are
formed: α− and β−D-aldose sugars, e.g., linear D-glucose cyclizes –>cyclic α−D-glucose (+112°) and cyclic β−D-
glucose (+19°), an anomeric pair with a 1:2 ratio of α:β forms (+52.5°) [Note, racemic pairs have a 1:1 ratio, they
have no net optical rotation.]
11
An epimer is a pair of sugars that differ at only one asymmetric carbon, e.g., D-glucose and D-mannose have opposite
configurations at C2
and glucose and galactose differ only at C4
.
12
In Fischer projection, the bottom most C* center of all sugars relates to C2
of glyceraldehyde and defines the sugar as
D or L. [The sole C2
* of glyceraldehyde (simplest aldose sugar, also named glyceric aldehyde) exits in two stereo
isomer forms: C2
–OH (on right side) defines D-form, (left) HO–C2
defines the L-form. All the D-aldose sugars (4-, 5-,
6-, 7-carbons) are considered derivatives of D-glyceraldehyde by adding one CH2OH at a time; all L-sugars are mirror
image molecules and are derived from L-glyceraldehyde.]
13
Each C* center is asymmetric and rotates polarized light left or right depending upon which one of the
configurational isomers is being measured, if both are present, racemate pair (1:1 ratio), no net rotation occurs (unless
another structural influence shifts the ratio higher or lower).
14
Reference glyceraldehyde: D-glyceraldehyde rotates polarized light rightward (dextro, [α]D = +13.5°) and L-
glyceraldehyde rotates polarized light leftward (levo, [α]D = –13.5°). More complex sugars, aldopentoses and
aldohexoses may give different rotations depending upon the summation of all the C* ( – or + ) rotations. [ Note:
dextro and levo are also notated as, d and l, respectively, e.g., l-lactic acid or d-lactic acid.
15
No, the “D” and “L” prefixes have no relationship to the direction of optical rotation. D and L simply designate
spatial relationship of the groups on the penultimate C* of the compound in reference to the D and L forms of
glyceraldehyde.
16
In a meso stereoisomer, two halves of the molecule are mirror images. Such a diastereomer is uniquely optically
inactive; the mirror halves constitute a racemic mixture, thus the optical rotation of one halve is reversed

(cancelled) by the second half.
17
The simplest example of a meso versus diastereoisomers comparison is tartaric acid (2,3-dihydroxy-1,4-succinic
acid), which has two middle C*s. In Fischer projection, the top and bottom carbon are identical (COOH). The
configuration of the –OH group on C2
and C3
are: left-right (I), right-left (II), and left-left (same as right-right),
respectively. Form I is levo- or l- or D-tartaric; form II is dextro- d- or L-tartaric, and form III is meso tartaric or m-
tartaric.
18
Living systems operate at constant temperature (isothermally) and constant pressure (isobarically) and cannot
convert heat energy directly into work as an engine does. Enthalpy (H) is the heat energy consumed or released in
a system at constant pressure. Entropy (S) is the energy that is unavailable to do work and is lost to disorderliness
of a system, entropy increases as temperature increases. Free energy (G) is the energy of a system that is available
to do work, at constant temperature and pressure, so it is useful in studying the bioenergetics of living systems.
Activation energy (Eact) is that amount of energy molecules most possess before they are capable of reacting.
Potential Energy is the energy of a molecule due to its position. Only the change (∆) in H, S, Eact is measurable
and has practical significance. [Potential energy is converted to Kinetic energy while the molecule is moving from
its original position to another. As a ball rises in the earth’s gravitational field, kinetic energy is converted to
potential energy – maximal at the instant the ball is suspended –before descending; while descending, the potential
energy is converted to kinetic energy (motion].
19
The more random disorder (the higher the entropy, S) in a system, the less energy is available to do work. Live
systems expend energy to organize molecules into highly organized functional structures and systems (membranes,
filaments, organelles, DNA sequences of specific order, etc.). Reversible reactions rarely reach equilibrium in vivo
so entropy is kept lower than at death, whereupon all equilibrium reactions tend towards equilibrium, and entropy
is maximized. The energy used to create orderly DNA sequences is released as DNA is hydrolyzed to disordered
nucleotides moving with Brownian motion in solution. The probability of the nucleosides randomly reorganizing
back into the original ordered sequence is highly improbable, the energy lost to entropy prevents it. Spontaneous
regeneration of life from thermodynamic death is virtually improbable, although, theoretically it is not entirely
impossible.
20
Assembly of monomer units into polymeric sequences increases orderliness and decreases entropy, hence
glycogenesis, FA synthesis, and the synthesis of proteins, DNA and RNA have lower entropy than their
corresponding monomers.
21
Assembly of monomers decreases entropy, disassembly of polymers increases entropy. Therefore, degradation of
glycogen, fatty acids, proteins, DNA and RNA to glucose, acetyl CoA, amino acids, deoxyribonucleotides and
ribonucleotides, respectively, decreases orderliness and increases disorderliness, so entropy increases during the
processes of glycogenolysis, β-oxidation, proteolysis, and hydrolysis, respectively.
22
Nucleophilic attack by an alcoholic O: (or, amino N: , mercapto S: ) from above or below a planar, trigonal,
electron deficient C of an aldehyde (R–CH=O, or ketone RR'–C=O) forms a tetrahedral product. Four different
chemical groups are bonded to the anomeric C in the hemiacetal so it an asymmetric (C*). If attack from below or
above is equally probable (no structural restraints) then a pure 1:1 ratio of enantiomeric isomer products forms. In
aldoses such as glucose, the C5
– ÖH attacks intramolecularly yielding a stable 6-membered ring (Haworth diagram)
held by a hemiacetal linkage. C1
is bonded to four different chemical groups, is asymmetric (C*). Ignoring the
reaction mechanism, the aldehydic C=O becomes C1
–OH in the hemiacetal group. Attack from above yields the α-
anomeric configuration (α-OH) under the ring, in Haworth projection); attack from above yields the β-OH anomeric
configuration.
23
Refer to study answer to Question 2[1]. In forming the intramolecular ring, the aldoses are expected to gain an
additional asymmetric carbon (optically active) in the resulting hemiacetals and hemiketals. Thus, aldose D-glucose
(4C*) ring closes –> α−D−glucose (5C*) + β−D−glucose (5C*); and ketose D-fructose (3C*) –> α−D−fructose (4C*)
+ β−D−fructose (4C*). D-ribose (3C*) –> α/β-D-ribose.
24
The process of mutarotation opens and closes the ring of sugars again and again. If freshly dissolved pure α (or β), is
observed through a polarimeter, initial degrees of polarized light rotation slowly changes until an unchanging reading
is achieved, i.e., an equilibrium mixture of α/β anomers is present. [However, in α-glucose, the OH groups are
crowded together (axial, flagpole interactions) above and below the ring; in the β-anomer, these bulky groups point
outward in the plane of the ring (equatorial) so steric crowding is minimal, the β-glucose is more stable (lower free
energy). For glucose, a pure 1:1, α/β, racemate mixture is not formed, instead a 1:2 (α/β) ratio is established at
equilibrium.] Closed-ring hemiacetals and hemiketals react with hydroxyl ions in solution, at physiological pH,
thereby reverting back to the aldehydic (–CHO) or ketone (C=O) ring-open form; thus, OH–
ions catalyze the
mutarotation rate upwards of about 40,000-fold! In contrast, acetals and ketals are very stable to OH–
ions (because
the anomeric carbon is linked to an –OR group not an –OH). Hence, disaccharides and polymers with α-acetal/ketal
linkages are very stable (don’t hydrolyze readily and are excellent for storage of glucose fuel (glycogen, starch).
Similarly, β−acetal linkages (cellulose in wood) are stable and strong polymeric molecules. [Note: in a polymer
(starch, glycogen, or cellulose), the end glucose residue has a free hemiacetal or ketal group and can mutarotate,

while all the other glucose residues in the polymer will not.] Common table sugar, sucrose is an acetal/ketal
combination: glucose-α1–β2-fructose; both anomeric carbons are in the one joining linkage, this disaccharide
doesn’t mutarotate!
25
Yes, the nucleoside components contain N−β−D–ribose in an N-acetal linkage to adenine, cytosine, guanine, or
uracil in RNA, and N−β−D–deoxyribosides of adenine, cytosine, guanine, or thymine in DNA.
26
Direct structural correspondence of L-amino acids to L-glyceraldehyde. Some bacteria and antibiotics use D-amino
acids.
27
See Fig 2.3 in Baynes and Dominiczak, Medical Biochemistry, for a list of structures, then Fig. 2.5 for those that are
acidic or basic according to the side-chain functional group. Which amino acids have acidic carboxyl –COOH; basic
amine –NH2; imidazole (histidine :N-ring), guanidino (arg). Also see Fig 2.7 for conjugate acid/base forms and pKa
values.)
28
Amino acids are amphoteric molecules, they have at least one basic and acidic group. Upon dissolving glycine in
water, for example, the α-NH2 amino group (pKa 9.8) becomes protonated to –NH3
+
ammonium; the α−COOH (pKa
2.4) ionizes to –COO–
; both ionic groups define a zwitterion (double ion) with net charge (0) at pH7.5. [ ]
For the Asp and Glu, the side-chain –COOH (pKa 3.9) ionizes yielding a net (–1) charge at pH 7.5. For lys, his, an
arg, these become protonated yielding a net (+1) charge at pH 7.5.
29
At pH 2 all amino acid carboxyl groups are COOH, all basic groups are protonated. Depending on the pKa of each
group, as hydroxyl ions are added, the pH changes from 2 to 12, each acid and base group is titrated in order of their
increasing pKa value. At pH 12, all acids groups are COO–
and all protonated bases are now in free-base form (e.g., –
NH2). At pH 2, most amino acids move to the anode, each will not move when the pH equals their isoelectric point, as
pH becomes increasingly basic, the amino acids will begin to move to the cathode, respectively. See Fig. 2.6 in
Baynes for the titration curve describing the progression of cation to zwitterion to anion of alanine, as an example of
a simple amino acid. Some amino acids have a third acid or basic group on their side chain. Their titration curves are
slightly more complex, but manageable).
[Electrophoretic migration of the 20 amino acids is pH-dependent on either side of their pI isoelectric point: (a)
simple amino acids: asn 5.41, gln 5.65, ser 5.68, met 5.75, gly 5.97, val 5.97, leu 5.98, phe 5.98, ala 6.02, ile 6.02 (2
C*), thr 6.53; (b) acidic amino acids: asp 2.97, glu 3.22; (c) basic amino acids: lys, 9.74, arg 10.76; (d) other ionizable
side chain groups: cys 5.08, tyr 5.65, trp 5.88, pro 6.10, his 7.58. Again, lower acidity moves them to the (−) anode,
higher to the (+) cathode. The pI is the average of the 2 or 3 pKa values. The (a) group give dipolar zwitterions
between pH 3 and 8 and barely migrate except at their isoelectric point (zero net charge, no movement). At
physiological pH, the net charge of free amino acids and when in a polypeptide is given for reference:
At pH 7.5, free amino acids, net charge (0): asn, gln, ser, met, gly, val, leu, phe, ala, ile, thr, his, cys, tyr, trp,
pro
two (−1): asp, glu
two (+1): lys and arg.
At pH 7.5, within a polypeptide, zero charge (0): asn, gln, ser, met, gly, val, leu, phe, ala, ile, thr cys, tyr, trp, pro
(−1): asp, glu, his
(+1): lys, arg. ]
30
The 20 amino acids given in footnote 28 are always incorporated into proteins during synthesis of their primary
structure. Specific amino acids (13) undergo posttranslational modification in certain proteins (see Fig 2.3) so the
number and variety of such modifications is complex. Methylations (lys, arg), phosphorylations (ser, thr, tyr),
carboxylations (glu), disulfide oxidations (cys) amidations (asp, asn, glu, gln), and hydroxylations (pro phe, tyr) are
some commonly encountered post translational modifications.
Some pathways create/consume other amino acids, e.g., ornithine, citrulline, argininosuccinate (urea cycle),
homocysteine (from S-adenosyl methionine), β-alanine (pyrimidine catabolism), GABA (from glu), and many
others.
31
A very complex subject. See Fig 2.12 in Baynes for four major sets of side-chain interactions. The 3D-folding of
proteins with more than about 200 amino acids consists of several smaller folded units designated as domains such as
alpha-helix, pleated-sheets, random coil, and others. These and other 3D tertiary (3°) structures of a protein are
stabilized by side-chain functional groups: covalent sulfhydryl bonds (cys-S—S-cys), hydrogen bonds (O–H•••N),
salt bridges (–COO–
•••H+
NH2–) and hydrophobic interactions (e.g., phe-phe, leucine zippers, zinc fingers, etc.). (See
Baynes Ch 2 under Tertiary Structure, Quaternary structure headings). Solvent effects, influenced by salts, and
other substances can be important. Some or all of these properties can be involved in quaternary structure, e.g.,
tetrameric hemoglobin (α2β2)
32
The nonpolar hydrophobic amino acids (gly, ala, leu, ile, val. phe, met, etc.) associate in hydrophobic pockets inside
the protein, water is excluded into the surrounding solution. The polar hydrophilic and acid base side-chain amino
acids (are usually on the surface in contact with water, also anions and cations of a wide variety. Some domains are
folded to expose a hydrophobic surface (e.g., membrane proteins, leucine zippers).

33
Glyco- and lipoproteins can have sugars and lipids bonded to the side-chains of ser, thr, try, hyp, lys, etc.). In
Baynes, see Fig 17.2; 24.1, 2, 3, 4; 26.4, 6, 12.
34
Classification: (a) Fatty acids are long chain hydrocarbons with a terminal carboxylate (not found free but always in
ester linkage with triple alcohol glycerol because free fatty acids are soaps and would dissolve cell membranes and
organelles) or are a in thioester linkage with CoA, ‘activated’ fatty acid, (b) triglycerols (fuel energy) are most
abundant, [also waxes: fatty acid esters of alcohols other than glycerol], (c) phospholipids (membrane structures;
derivatives of glycerol phosphate, diesters most abundant, second, derivatives of sphingosine phosphate, which
contain an esterified fatty acid (FA) and a nitrogenous base (choline, ethanolamine) which may also be esterified with
a phosphate. (d) Nonphosphorylated lipids (1. cerebrosides, glycolipids: derivatives of sphingosine having a FA and
hexose substituent. 2. Sulfolipids: derivatives of sphingosine, FA and sulfated hexose substituent. 3. Gangliosides:
derivatives of sphingosine, FA, hexosamine, hexose and sialic acid. 4. Proteolipids: complexes of lipid and protein. 5.
Steroids: derivatives of cyclopentanoperhydrophenanthrene.
35
Triacylglycerol or triacylglycerides or triglycerides are idea as Fuel: because the fatty acids are essentially
polymerized hydrocarbon, (CH2) molecules, that metabolic oxidation converts to CO2
and about 9 kcal/gram of FA,
the highest caloric value compared with carbohydrates and proteins (both about 4 kcal/gram). Solubility: extractable
by ether, chloroform or alcohol. FA less than C6 are soluble in water (e.g., acetic – butyric acids). Density: as low as
0.7 g/ml makes them lighter than water. Melting points: 1C to 9C are below body temperature, 10Cs and more are
likely solids; cis C=C bonds lower mp enough to be liquid oils at body temperature – that’s important for membrane
fluidity. Insulator: effective thermal and electrical. Padding/supporting: the kidneys are surrounded by lipid fat.
Phospholipids form bilayer sheets in water, and if shaken will form spherical bilayers filled with solvent (water)
called micelles, which are a primitive model of a cell or cell organelles that serve to separate (partition) molecules
and structures with different compositions and functions. Further considerations of lipids and membranes are taken up
in Cell Organelles Course by Prof. Roy, refer to your notes.
36
Phospholipids (or phosphatides) are a heterogeneous group of compounds found in virtually every living cell and
may be the chief cellular lipid component. In general, natural phospholipids have the L-configuration, so phosphatidic
acids contain L–α– phosphatidic acid with two FA esterified to the β and γ-carbon of glycerol. The phosphate may be
esterified to choline (lecithins), ethanolamines (cephalins), both are the most abundant (phosphatidyl-inositol, -serine,
-glycerol, also occur). In contrast, sphingolipids have a unique core molecule, sphingosine, D-erythro-1,3-dihydroxy-
2-amino-4-trans-octadecen (18 carbon chain length). Hydrolysis of sphingomyelins yields sphingosine, phosphate, a
fatty acid, and a nitrogenous base (mostly choline, although ethanolamine is found too).
37
The relationship between the H, A, and B blood-group substances (see Fig 25.15 in Baynes) relates to the terminal
oligosaccharide linked via other sugars to proteins and lipids on the red cell membrane. The H-substance has protein
and sphingolipid attached. Individuals with type A blood designation have Gal-N-Ac-α1,3 attached to the galactose
of H-substance to form the A-type glycolipid. Type B have Gal-α1,3 to the galactose of H-substance to form the B-
type glycolipid. Type AB have both Gal and Gal-N-Ac attached to the galactose of H-substance. Type O have
neither sugars added to the galactose of H-substance. In each blood type: A, AB, and B, a specific transferase gene is
expressed that adds the specific sugar(s); neither gene is expressed in type O individuals, who lack both enzymes.
38
See Fig 28.3 in Baynes. Atoms incorporated onto purine ring of IMP derive from : N9
-glutamine, C4,5
N7
-glycine, C8
-
N10
-formyl THFA, N3
-glutamine, C6
-CO2, aspartate, C2
-N10
-formyl THFA yields hypoxanthine ring of inosine-5P
(IMP).
39
See Fig 28.4 in Baynes. AMP <– adenylosuccinate <– IMP –> XMP –> GMP. Asp is used to make AMP; NAD+
,
then gln are used to make GMP. Specifically: Rxs
11. IMP + asp + GTP5
–> adenylosuccinate (similar to argininosuccinate in urea cycle)
12. adenylosuccinate –> AMP + fumarate
11. IMP + NAD+
–> XMP + NADH
12. XMP + gln + ATP5
–> amide (rearranges) to imide of guanine in GMP.
40
Five specific steps involve coupling to ATP hydrolysis for synthesis of an amide in each case. Amides require
high energy input usually obtained from coupled to ATP hydrolysis. The following 12 steps review purine de
novo synthesis. The four for hypoxanthine and ATP or GTP coupled reactions for AMP and GMP are bold. Five
total for AMP and GMP.
1. PRPP + Gln –> 5P-ribosyl-1-amine + glu + PPi
2. 5P-ribosyl-1-amine + gly + ATP1
–> glycinamide rt + ADP + Pi [note: 5P-ribosyl = ribonucleotide = rt]
3. glycinamide rt + N10
-f-FH4 –> formyl-glycinamide rt + FH4
4. formyl-glycinamide rt + gln + ATP2
–> f-gly-amidine rt + glu + ADP + Pi [amidine is a 2N amide, C=N
substitutes for C=O]
5. f-gly-amidine rt + ATP3
(ring closure) –> 5-NH2-imidazole rt +ADP + Pi [closed-ring amide that rearranges to
imidazole]
6. PR-5-NH2-Im rt + CO2 –> 5-NH2-4-carboxyate-Im rt
7. 5-NH2-4-carboxylate-Im rt + asp + ATP4
–> 5-NH2-Im-4-N-succinocarboxamide nt + ADP + Pi
8. 5-NH2-Im-4-N-succinocarboxamide nt –> 5-NH2-Im-4-carboxamide nt + fumarate

9. 5-NH2-Im-4-carboxamide nt + N10
-f-FH4 –> 5-f-NH2-Im-4-carboxamide rt + FH4
10. 5-f-NH2-Im-4-carboxamide rt + H2O –> hypoxanthine rt = inosinate = IMP
11. IMP + asp + GTP5
–> adenylosuccinate (similar to argininosuccinate in urea cycle)
12. adenylosuccinate –> AMP + fumarate
11. IMP + NAD+
–> XMP + NADH
12. XMP + gln + ATP5
–> amide (rearranges) to imide in guanine of GMP.
41
N10
-formyl-THFA supplies C8
and C1
in hypoxanthine in IMP synthesis; CO2 supplies C6
of IMP; SAM for GpppN-
mRNA –> m7
GpppN-mRNA, other RNAs and proteins.
42
Glutathione (GSH) is L-γ-glu-cys-gly [note the side chain –COOH of glu is bonded to cys]. The cys-SH is the active
antioxidant functional group, it supplies electrons thereby preventing other molecules (proteins) from being oxidized
(loss of electrons brought about by interaction with reactive oxygen species. By donating electrons GSH becomes
oxidized instead and it forms dimer GSSG. There are two tissues that must deal with high levels of oxidative insult
that are highly differentiated, the red cell and the eye lens, both have GSH levels between 6-8 mM. Red cells are
constantly exposed to high levels of oxygen. In contrast the pO2 in lens is so low (oxygen diffusion from vascularized
retina) that it can’t be accurately measured. Lens oxidation is due to photooxidation by ultraviolet radiation. Since
visual clarity must be maintained, and all lens proteins are present throughout life (no turnover), antioxidant
protection by GSH is absolutely essential to prevent cataracts (opacity, due to light scattering by oxidized proteins
and other physicochemical effects).
43
In Baynes, last topic, “A small fraction of triose phosphates produced during metabolism spontaneously degrades to
methylglyoxal” CH3-CO-CHO, adjacent, highly reactive aldehyde-ketone groups “methylglyoxal (MG) reacts with
amino, guanidino (arg), imidazole (his) and sulfhydryl (cys) groups in proteins, leading to enzyme inactivation and
protein crosslinking. Methylglyoxal is also formed during metabolism of acetone (CH3-CO-CH3) and glycine. The
glyoxalase pathway (Fig 11.15) is a 3-Rxn pathway to detoxify methylglyoxal to D-lactate. MG and GSH form a
hemithioacetal (pyruvate-SG) that glyoxalase I rearranges to D-lactate-SG that glyoxalase II hydrolyzes to D-lactate
and releases GSH to be used again, i.e., MG + GSH –> MG-SG (glyoxalase I) –> Pyr-SG (+ H2O, glyoxalase II)–>
D-lactate + GSH
44
Oxygen is the indispensable final recipient of metabolic electrons. When reduced by cytochrome a3 to water all latent
energy in the larger perspective that is derived ultimately from photosynthesis has been converted to free energy to
drive the body, any energy difference is lost to other thermodynamic energies, such as heat and randomness, relate to
the efficiency of the bioenergetics of life processes. Any diminution of oxygen supply entering the mitochondria
proportionately diminishes the entire oxidative metabolic apparatus, which rapidly manifests as hypoxia in all
vascularized tissue cells, especially the brain.
Molecular oxygen is relatively inert, but is a strong oxidizing agent. Iron heme and membrane lipids are easily
oxidized. All oxidases and oxygenases (metalloenzymes) use molecular O2 and produce partially reduced reactive O2
species (ROS) such as oxygen superoxide radical anion (O2
•–
), its protonated form (hydroperoxy radical HOO•
,pKa
≈ 4.5), and hydrogen peroxide (H2O2) that are more reactive then O2 and are precursors to strongly oxidizing species
such as hydroxyl radical (OH•
) and metal-oxo complexes (Baynes Fig 11.10).
Functional hemoglobin (Hb) contains ferrous iron (Fe2+
) which binds O2. Hb can spontaneously produce O2
•–
in a
side reaction associated with O2 binding that converts hemoglobin (Fe2+
, red) to methemoglobin (Fe3+
, reddish
brown). MetHb may precipitate in the RBC, forming inclusions known as Heinz bodies, and may also release heme,
which reacts with O2
•–
and H2O2 to produce OH•
and reactive iron-oxo species. [ROS species form lipid peroxides that
decompose to reactive carbonyl species that react with proteins, damaging the integrity of the cell membrane and the
activity of transporter proteins, collapsing ion gradients and leading to cell death.]
45
Both separate salvage Rxns uses PRPP to supply ribose-5P: Enz: adenine-phosphoribosyltransferase: ade –> AMP;
Enz: hyp-gua PRtase: hyp or gua –> IMP or GMP. Both enzymes convert free base to nucleotide in one step. The
most prevalent deficiency (HGPRTase) results in excessive oxidative loss of hyp and gua to uric acid that presents as
hyperuricemia. The consequences come from the sparing solubility and needle-sharp sodium uricate crystals. These
most easily appear in the cooler joints of the hands and feet leading to acute gout-like episodes beginning in middle
age in men. If brain levels of HGPRTase below 1%, uncontrollable psychiatric, self-mutilation occurs, with life-span
limited at best to teenage years if untreated chiefly due to renal failure.
46
Xanthine oxidase (XO, a molybdenum (Mo6+
-iron-containing flavoprotein) oxidizes hypoxanthine –> xanthine –>
uric acid using molecular oxygen (which is reduced to H2O2 , then decomposed to water and O2 by catalase). Once
XO acts on allopurinol as a substrate, its oxidation product, alloxanthine (oxipurinol), binds strongly to XO, inhibits
the enzyme, hence the designation as a suicide inhibitor. Allopurinol is an analog of hypoxanthine in which C8
and
N9
are switched - the two ring N’s next to each other. [Allopurinol prevents Mo4+
reoxidization back to Mo6+
(active
enzyme).
47
With XO inhibited by allopurinol, PPRP levels are higher in gout (may approach normal levels) salvage operates
more normally so free ade, hyp, and gua bases go back into AMP, IMP, and GMP nucleotides for continued usage
rather than oxidative loss to urate. Without allopurinol, purine base levels decrease and insoluble uric acid increases

(hyperuricemia). Additionally, the high PRPP levels stimulate more de novo purine nucleotide synthesis that leads to
further uric acid increases (in Lesch-Nyhan syndrome of up to 50 mg urate/kg body weight/day) above the normal
output of 10 mg urate/kg body weight/day.
48
ATP hydrolysis.
49
Creatine phosphate (creatine-P). This secondary, high-energy reserve (∆Gº'CP = – 12.0 kcal/mol compare to (∆Gº'ATP
= – 7.3) converts ADP to ATP + creatinine.
50
The phosphate of creatine-P is in a very high-energy bond (∆Gº'CP = – 12.0 kcal/mol). The quanidino group of
creatine (from arg) makes an N-anhydride (similar to O-acid anhydrides, e.g., acetyl anhydride, carbamoyl-P), all of
which have a high (∆Gº') of hydrolysis. When the creatine-P cyclizes, the attacking COO (from the other end of the
molecule) forms an cyclic amide and the stable leaving group, Pi, leave sufficient free energy to phosphorylate ADP.
51
Creatinine is the cyclic N-anhydride product of creatine-P, it has no other metabolic use and is excreted from the
plasma into the urine.
52
Anaplerosis reactions convert metabolites to TCA cycle intermediates to replace those diverted out into other
synthetic pathways (e.g., succinyl CoA into heme synthesis). The most immediate reaction supplies OAA (from
pyruvate via pyruvate carboxylate), which together with pyruvate starts the cycle and ends by regenerating OAA. The
next anaplerotic enzyme (glu transaminase) converts glutamate –> α-ketoglutarate; then malic enzyme converts
cytoplasmic pyruvate –> malate which enters the mitochondrion. Thus, anaplerosis ensures that OAA is available for
continued TCA function and also ensures that gluconeogenesis can occur using the carbon skeletons of glucogenic
amino acids (when glucose supplies are diminished).
53
Without PCase to convert pyruvate to OAA, pyruvate is converted to lactate, both accumulate. Increased cellular
lactic acid leaves and enters the plasma acidifying it, i.e., causing lactic acidosis (one type of metabolic acidosis).
54
Without PCase, high pyruvate leads to increased acetyl CoA via pyruvate dehydrogenase, which then funnels into
fatty acid synthesis. Gluconeogenesis is inhibited, so the increases pyruvate goes to acetyl CoA increasing lipogenesis
significantly.
55
The pentose shunt supplies the NADPH. [Note, if gluconeogenesis is inhibited, then glucose is available to enter the
pentose shunt yielding 2 NADPH per glucose and the carbons reenter glycolysis to give even more pyruvate, hence,
acetyl CoA for continued lipogenesis.]
56
The free energy content of a substrate (or its product) cannot be measured directly, only the difference or change
(∆G) of free energy content between substrate and product can be measured. Enthalpy change (∆H) in heat gained or
lost among the molecules of a reaction system, at constant pressure, decreases or increases the temperature of the
reaction system surroundings (water, cytosol, mitosol, nucleosol, etc). The biochemical apparatus of the cell cannot
convert heat per se into work, as a mechanical engine can. Thermal homeostasis mechanisms dispose of the heat
through respiratory, circulatory, and perspiration mechanisms but most useful metabolic work would not occur
otherwise (a hibernating bear). American chemist, Willard Gibbs developed the thermodynamics of free energy
which relates the heat gained or lost in a reaction at constant pressure (isobaric) but reconciled it with the condition of
constant temperature (T = is constant, isothermal), which are the conditions of biochemical reactions in animals with
thermal homeostasis regulation. Hence, ∆G = ∆H - T∆S took into account the unusable difference in (∆H) heat as
related to changes in system randomness (∆S) at a particular temperature. What was left was ∆G, energy free for
useful physico-chemical work or achievement.
57
Add algebraically Rx II + Rx I = (– 7.3) + (+ 3.3) = – 3.0 kcal/mol, the net energy difference is exergonic for glucose
phosphorylation by hexokinase (or glucokinase).
58
Exergonic: Rx I; endergonic: Rx II.
59
Catabolism is exergonic; anabolism is endergonic; overall metabolism (catabolism + anabolism) is exergonic.
60
A double reciprocal plot graphs 1/x versus 1/y. The Lineweaver-Burk plot graphs 1/[S] versus 1/V, respectively, and
is advantageous, for the usual hyperbolic curve of the typical Michaelis-Menten plot is thereby linearized. The y-
intercept gives 1/Vmax, the x-axis gives –1/Km. Simple calculation gives Km and Vmax.
61
The Km is the substrate concentration ([S]) at which the reaction rate is half the maximal velocity (Vmax/2). As [S]
increases, reaction rate (V) increases and approaches the maximal velocity possible, Vmax, asymptotically (for the
amount of enzyme present, if the amount of enzyme doubles the rate doubles). Km is also a measure of the affinity of
the substrate for the enzyme.
62
The initial velocity (vo) gives the most accurate experimental measure of rate at the initial [S], which is known most
accurately. Intermediate v values are more difficult to determine because of experimental uncertainties. In reference
to the Michaelis-Menton hyperbolic curve, the section of the rate curve where [S} is below the Km is first order
because the rate is proportional to [S]. The part of the rate curve corresponding to more than 5- or 10-times [S] above
the Km is demonstrating zero order kinetics because the enzyme is working as fast as possible, independent of [S],
because S is so abundant that any further addition of S does not increase the reaction rate significantly.

63
Glycolysis is the central metabolic pathway for oxidizing glucose to smaller carbon fragments that have diverse
anabolic and catabolic fates.
Anaerobic glycolysis also yields 2 net ATP, while aerobic glycolysis also yields 8 net ATP.
are produced, 2 ATP are consumed . It serves as a preparatory pathway for either completing the oxidation (TCA) or
storing the carbons in fatty acids (FA synthesis) as a depot fuel, or other uses (cholesterol, etc). When operating
anaerobically it recovers only about 5% of the energy available from glucose that can be extracted, when operating
aerobically, reduced NADH, produced by glycolysis, is oxidized with oxygen involvement (aerobically) in a
mitochondria to extract nearly 40% of the energy in glucose.
64
Phosphorylation of F6P to F16BP by PFK-1 commits irreversibly the 6-carbon skeleton to oxidative glycolysis. The
phospho-sugars in reactions preceding fructose-6P can flow into other pathways, so their carbon skeleton is not
committed to glycolysis. Once F6P is acted upon by PFK-1, the only fate of F16BP is cleavage by aldolase and
further glycolytic oxidations of each 3-carbon fragment to pyruvate (or lactate).
65
Pyruvate is the major product of aerobic glycolysis, lactate is the major product of anaerobic glycolysis. ATP is
also a major product of both glycolytic process, anaerobic glycolysis yields a net of 2 ATP whereas aerobic
glycolysis yields a net of 8 ATP (due to mitochondrial participation). [Both glycolytically produced NADHs have
their electrons shuttled into the mitochondrion to yield an additional 6 net ATP].
and the pyruvate carbon skeleton is further oxidized in the mitochondrion to 3 CO2 and an additional 15 ATP are
produced from reduced coenzymes
66
Lactate dehydrogenase (LD) prevents metabolic collapse by recycling the catalytic amount of NADH to NAD+
so
glycolysis continues regenerating ATP from ADP. This is made possible by reducing pyruvate (ketone) to lactic
(alcohol).
67
Mitochondria.
68
Pyruvate kinase phosphorylates ADP to ATP using the high –∆G of PEP hydrolysis of the enol that yields pyruvate.
69
Anaerobic glycolysis (yields net of 2 ATP per glucose) versus aerobic glycolysis (yields net of 8 ATP per glucose).
70
The red blood cell can only produce glycolytic lactate! It lacks mitochondria! Hence, the RBC is a continuous, major
source of plasma lactate. As the simplest of cells, the net 2 ATP yield is sufficient to meet RBC metabolic energy
needs because cell’s role is transporting and delivering oxygen is maximized by having no need for oxygen.
71
The muscle cells constitute the major tissue mass of the body. When working anaerobically produce massive
amounts of lactate which enters the plasma during strenuous exercise.
72
Free glucose and glucose released from polymeric carbohydrates (starches) in foods are absorbed by the intestines
and transported via the portal vein into the liver. Glucose utilization requires phosphorylation. Hexokinase has low Km
for glucose and is G6P product inhibited, which is adequate for muscle cell glycogenesis and glycolysis needs, but
inadequate for liver glucose metabolism needs, which must supply its own needs as well as supply the brain and all
other tissues. Unlike muscle cells, liver cells also have hexokinase isozyme IV (glucokinase), which has better
kinetics: high Km and no G6P product inhibition so G6P flows easily and rapidly into liver glycogenesis and
glycolysis. At rest after a meal, a 70 kg man will store 200 g of glucose as liver glycogen and 150 g glucose as muscle
glycogen, but overnight only 80 g of glucose in liver glycogen will remain. The other 120 g of glycogen glucose was
released by the liver to supply the brain and other tissues with glucose overnight. During waking hour activities,
additional amounts of glucose is oxidized by the liver for varied metabolic needs.
73
Gene expression of the liver glucokinase gene is induced by higher than usual dietary glucose loads if sustained over
several days thereby enabling the liver to adapt to extraordinarily elevated dietary glucose and higher than usual
hyperglycemia. The other enzymes listed in the question are part of glycolysis.
74
The acetal functional group (C bearing two OR groups) defines O-glycosides (e.g., glycogen and cellulose). It
contains two stable ether-like bonds (C–O–Ca
and C–O–Cb
) on the anomeric C* so glycosides are stable, it will not
hydrolyzed on its own. One OR is in the sugar ring, the second OR is a linked sugar residue (replaces H in the
hemiacetal of free glucose). There are two possible stereochemical isomers (α and β at the C*) for the O-sugar: either
above or below the ring, respectively. Glycoside synthesis and hydrolysis enzymes are stereospecific for α- or β-
glycoside anomer linkage, i.e., α1,4 (starch, amylase) and α1,6 (glycogen, debranching enzyme, then amylase)
or β1,4 (cellulose, cellulase). Dietary starch (fuel) digestion begins in the mouth with salivary α−amylase, later in the
gut with pancreatic amylase. We lack cellulase, so the beta-cellulose polymer fibers are eliminated in feces.
Cellulose beta-structure provides considerable hydrogen bonding among its polar groups thereby conferring strength
to the fibers for load bearing in plants and trees. [During polymerization, the C1
of the incoming glucose links to
C4
OH of the terminal (nonreducing) glucose of the existing polymer (or to C6
OH, during branch creation); subsequent
additions occur at both C4
OH ends.]
75
Each branch introduced doubles the substrate concentration of nonreducing ends to which new residues can be
added. When 7-11 residues are added from the last branch, the outer four residues are moved to C6
of the 5th
residue
to create a branch. Once branched, the original molecule has 2, then 4, 8, 16, 32, 64, 128, 256, 512, 1024 termini after

200525160 nbde-part-i-biochem-review-and-study-guide

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