3. CARBOHYDRATES
Hydrates of carbon [Cn(H2O)m]
Polyhydroxyaldehyde or polyhydroxyketone, or
substance that gives these compounds on hydrolysis
Most abundant organic compound in the plant world
Chemically made up of skeletal C,H which is usually
2x the number of C, highly variable number of O,
occasional N & S
Linked to many lipids and proteins
4. FUNCTIONS of
CARBOHYDRATES
Storehouses of chemical energy
Glucose,starch, glycogen
Structural components for support
Cellulose, chitin, GAGs
Essential components of nucleic acids
D-ribose, 2-deoxy-D-ribose
Antigenic determinants
Fucose, D-galactose, D-glucose, N-acetyl-D-
glucosamine, D-acetyl-D-galactosamine
5. SPECIFIC CARBOHYDRATES
Monosaccharides
Glucose (dextrose, grape sugar, blood sugar)
Can be stored as glycogen
Most metabolically important monosaccharide
Fructose (levulose)
Galactose (brain sugar)
Mannose
Targets lysosomal enzymes to their destinations
Directs certain proteins from Golgi body to lysosomes
7. CLASSES OF CARBOHYDRATES
Number of C
Triose, tetroses, pentose, hexose, heptulose
Number of saccharide units
Monosaccharides, disaccharides, oligosaccharides (2 to 10
units), polysaccharides
Position of carbonyl (C=O) group
Aldose if terminally located
Ketose if centrally located
Reducing property
Reducing sugars (all monosaccharides)
Nonreducing sugars (sucrose)
8. STRUCTURAL PROJECTIONS OF
MONOSACCHARIDES
FISCHER by Emil Fischer
(Nobel Prize in Chemistry 1902)
2-D representation for showing
the configuration of a stereocenter
Horizontal lines project forward
while vertical lines project towards
the rear
D (R or +) or L (S or -)
9. HAWORTH by Walter Haworth
(Nobel Prize in Chemistry 1937)
A way to view furanose (5-membered ring) and
pyranose (6-membered ring) forms of
monosaccharides
The ring is drawn flat and viewed through its edge
with the anomeric carbon on the the right and the
oxygen atom on the rear
14. REDUCING PROPERTY
Ketose O H
H OH- C
H – C – OH
H C OH
C=O Enediol O O-
R HO H OH- R
C
C
Aldose Oxidizing
H C OH
C agent R
R OH
Aldonate
15. ABO ANTIGENS
N-acetyl- D-galactose N-acetyl-
TYPE A
D-galactosamine D-glucosamine
Fucose
D-galactose D-galactose N-acetyl-
TYPE B
D-glucosamine
Fucose
D-galactose N-acetyl-
TYPE O
D-glucosamine
Fucose
16. POLYSACCHARIDES
STARCH
Storage carbohydrate in plants
Two principal parts are amylose (20-25%) &
amylopectin (75-80%) which are completely
hydrolyzed to D-glucose
Amylose is composed of continuous, unbranched
chain of 4000 D-glucose linked via α 1-4 bonds
Amylopectin is a chain of 10,000 D-glucose units linked
via α 1-4 bonds but branching of 24-30 glucose units is
started via α 1-6 bonds
17. GLYCOGEN
Energy-reserve carbohydrate in animals
Highlybranched containing approximately
106 glucose units linked via α 1-4 bonds & α
1-6 bonds
Well-nourished adult stores 350 g. of it
equally divided between the liver and
muscles
18. CELLULOSE
Plant skeletal polysaccharide
Linear chain of 2200 glucose units linked
via β 1-4 bonds
High mechanical strength is due to
aligning of stiff fibers where hydroxyl form
hydrogen bonding
19. ACIDIC POLYSACCHARIDES
Also called mucopolysaccharides (MPS) or
glycosaminoglycans (GAG)
Polymers which contain carboxyl groups and/or
sulfuric ester groups
Structural and functional importance in connective
tissues
Interact with collagen to form loose or tight networks
20. ACIDIC POLYSACCHARIDES
HYALURONIC ACID
Simplest GAG
Contains 300-100,000 repeating units of D-glucuronic
acid and N-acetyl-D-glucosamine
Abundant in embryonic tissues, synovial fluid, and the
vitreous humor to hold retina in place
Joint lubricant & shock absorber
HEPARIN
Heterogeneous mixture of variably sulfonated chains
Stored in mast cells of the liver, lungs and the gut
Naturally-occurring anticoagulant by acting as
antithrombin III and antithromboplastin
Composed of two disaccharide repeating units A & B;
A is L-iduronic acid-2-sulfate linked to 2-deoxy-2-sulfamido-D-
galactose-6-sulfate
B is D-glucuronic acid beta-linked to 2-deoxy-2-sulfamido-D-glucose-
6-sulfate
21. HEPARAN SULFATE
CHONDROITIN SULFATE
Most abundant in mammalian tissues
Found in skeletal and soft connective tissues
Composed of repeating units of N-acetyl galactosamine sulfate linked
beta1-4 to glucuronic acid
KERATAN SULFATE
DERMATAN SULFATE
Found in skin, blood vessels, heart valves, tendons, aorta, spleen
and brain
The disaccharide repeating units are L-iduronic acid and N-
acetylgalactosamine-4-sulfate with small amounts of D-glucuronic acid
22.
23. GLYCOLYSIS
The specific pathway by which the body
gets energy from monosaccharides
First stage is ACTIVATION
At the expense of 2ATPs glucose is
phosphorylated
Step #1
formation of glucose-6-phosphate
Step # 2
isomerization to fructose-6-phosphate
24. Step # 3
Second phosphate group is attached to yield fructose-
1,6-bisphosphate
Second stage is C6 to 2 molecules of C3
Step # 4
Fructose-1,6-bisphosphate is broken down into two C3
fragments
glyceraldehyde-3-phosphate (G-3-P) and
dihydroxyacetone phosphate (DHAP)
Only G-3-P is oxidized in glycolysis. DHAP is converted
to G-3-P as the latter diminishes.
25. ATP-YIELDING Third stage
Step # 5
Glyceraldehyde-3-phosphate is oxidized to 1,3-
bisphosphoglycerate; hydrogen of aldehyde is
removed by NAD+
Step # 6
Phosphate from the carboxyl group is transferred
to the ADP yielding ATP and 3-
phosphoglycerate
Step # 7
Isomerization of 3-phosphoglycerate to 2-
phosphoglycerate
26. Step # 8
Dehydration of 2-phosphoglycerate to
phosphoenolpyruvate (PEP)
Step # 9
Removal of the remaining phosphate to yield
ATP and pyruvate
Step # 10
Reductive decarboxylation of pyruvate to
produce ethanol and CO2
27. REACTIONS OF GLYCOLYSIS
STEP REACTION ENZYME REACTION ΔG in
TYPE kJ/mol
1 Glucose + ATP Hexokinase Phosphoryl -33.5
transfer
G-6-P + ADP + H+
2 G-6-P F-6-P Phosphoglucose Isomerization -2.5
isomerase
3 F-6-P + ATP Phosphofructo- Phosphoryl -22.2
kinase transfer
F-1,6-BP + ADP + H+
28. STEP REACTION ENZYME REACTION TYPE ΔG in
kJ/
mol
4 F-1,6-BP DHAP + GAP Aldolase Aldol cleavage -1.3
5 DHAP GAP Triose Isomerization +2.5
phosphate
isomerase
6 GAP + Pi + NAD+ Glyceraldehyde Phosphorylation +2.5
1,3-BPG + NADH + H+ -3-Phosphate coupled to
Dehydrogenase oxidation
7 1,3-BPG + ADP Phosphoglycer- Phosphoryl +1.3
3-phosphoglycerate +ATP ate kinase transfer
8 3-phosphoglycerate Phosphoglyce- Phosphoryl shift +0.8
2-phosphoglycerate rate mutase
9 2-phosphoglycerate Enolase Dehydration -3.3
PEP + HOH
10 PEP + ADP + H+ pyruvate + ATP Pyruvate kinase Phosphoryl -16.7
transfer
32. REGULATION OF TCA CYCLE
Pyruvate
- ATP, acetyl CoA & NADH
Acetyl CoA
Oxaloacetate Citrate
Malate
Isocitrate
Fumarate - ATP & NADH ICD
+ ADP
Α-Ketoglutarate
Succinate
Α-KGD
Succinyl
- ATP, succinyl
CoA CoA & NADH
33. BIOSYNTHETIC ROLES
OF TCA CYCLE
Pyruvate
Other amino
acids,
purines & Acetyl CoA
pyrimidines
Oxaloacetate Citrate Fatty acids,
sterols
Aspartate Malate
Isocitrate
Fumarate
Other
amino
Α-Ketoglutarate acids &
Succinate purines
Porphyrins, Glutamate
heme, Succinyl
chlorophyll CoA
34. NOTES TO REMEMBER
The unusual thing about the structure of N-
acetylmuramic acid compared to other
carbohydrates is the presence of a lactic acid
side chain.
Cell walls of plants are cellulosic (polymer of
D-glucose); bacterial cell walls consist mainly
of polysaccharide crosslinked to peptide
through murein bridges; and fungal cell walls
are chitinous (polymer of N-acetyl-β-D-
glucosamine)
35. Glycogen and starch differ mainly in the degree
of chain branching.
Enantiomers are nonsuperimposable, mirror-
image stereoisomers differing configuration
on all carbons while diastereomers are
nonsuperimposable nonmirror-image
stereoisomers differing only on two
carbons.
Fischer projection of glucose has 4 chiral
centers while its Haworth projection has 5
chiral centers.
36. Sugar phosphate is an ester bond
formed between a sugar hydroxyl and
phosphoric acid.
A glycosidic bond is an acetal which can
be hydrolyzed to regenerate the two
original sugar hydroxyls.
A reducing sugar is one that has a free
aldehyde group that can be easily
oxidized.
37. Major biochemical roles of glycoproteins
are signal transduction as hormones,
recognition sites for external molecules in
eukaryotic cell membranes, and defense as
immunoglobulins.
L-sorbitol is made by reducing D-glucose.
Arabinose is a ribose epimer, thus, its
derivatives ara-A and ara-C if substituted
for ribose act as inhibitors in reactions of
ribonucleosides.
38. Two best precursors for glycogen are
glucose and fructose.
Cellulose because of the β- bonding is linear
as to structure and structural as to role while
starch because of α-bonding coils with
energy storage role.
The highly branched nature of glycogen
gives rise to a number of available glucose
molecules at a time upon hydrolysis to
provide energy. A linear one provides one
glucose at a time.
39. The enzyme β-amylase is an exoglycosidase
degrading polysaccharides from the ends. The
enzyme α-amylase is an endoglycosidase
cleaving internal glycosidic bonds.
Dietary fibers bind toxic substances in the gut
and decreases the transit time, so harmful
compounds such as carcinogens are removed from
the body more quickly than would be the case with
low-fiber diet.
The sugar portions of the blood group
glycoproteins are the source of the antigenic
difference.
40. Cross-linking can be expected to play a role in the
structures of cellulose and chitin where mechanical
strength is afforded by extensive hydrogen bonding.
Converting a sugar to an epimer requires inversion
of configuration at a chiral center. This can only be
done by breaking and reforming covalent bonds.
Vitamin C is a lactone (a cyclic ester) with a double
bond between two of the ring carbons. The
presence of a double bond makes it susceptible to
air oxidation.
The sequence of monomers in a polysaccharide is
not genetically coded and in this sense does not
contain any information unlike the nucleotide
sequence.
41. Glycosidic bonds can be formed between the side
chain hydroxyls of serine or threonine residues
and the sugar hydroxyls. In addition, there is a
possibility of ester bonds forming between the side
chain carboxyl groups of aspartate or glutamate
and the sugar hydroxyls.
In glycolysis, reactions that require ATP are:
1. phosphorylation of glucose (HK,GK)
2. phosphorylation of fructose-6-phosphate (PFK)
Reactions that produce ATP are:
1. transfer of phosphate from 1,3-
bisphosphoglycerate to ADP (PGK)
2. transfer of phosphate from PEP to ADP (PK)
42. In glycolysis, reactions that require NADH are:
1. reduction of pyruvate to lactate (LDH)
2. reduction of acetaldehyde to ethanol
(alcohol dehydrogenase)
Reactions that require NAD are:
1. oxidation of G-3-P to give 1,3-DPG (G-3-PD)
NADH-linked dehydrogenases are LDH, ADH & G-
3-PD.
The purpose of the step that produces lactate is to
reduce pyruvate so that NADH can be oxidized to
NAD+ needed for the step catalyzed by
glyceraldehyde-3-phosphate.
43. Aldolase catalyzes the reverse aldol condensation
of fructose-1,6-bisphosphate to glyceraldehyde-3-
phosphate and DHAP.
The energy released by all the reactions of
glycolysis is 184.5 kJ mol glucose/mol. The energy
released by glycolysis drives the phosphorylation of
two ADP to ATP for each molecule of glucose,
trapping 61.0 kJ mol/glucose. The estimate of 33%
efficiency comes from the calculation (61.0/184.5) x
100 = 33%.
There is a net gain of two ATP molecules per
glucose molecule consumed in glycolysis. The
gross yield of 4 ATPs per glucose molecule, but the
reactions of glycolysis require two ATP per glucose.
44. Pyruvate can be converted to lactate, ethanol or
acetylCoA.
The free energy of hydrolysis of a substrate is the
energetic driving force in substrate-level
phosphorylation. An example is the conversion of
glyceraldehyde-3-phosphate to 1,3-
bisphosphoglycerate.
Coupled reactions in glycolysis are those reactions
catalyzed by hexokinase, phosphofructokinase,
glyceraldehyde-3-phosphate dehydrogenase,
phosphoglycerokinase, and pyruvate kinase.
45. Isozymes allow for subtle control of the enzyme to
respond to different cellular needs. For example, in the
liver, LDH is most often used to convert lactate to
pyruvate, but the reaction is often reversed in the
muscles. Having a different isozyme in the liver and
the muscle allows for those reactions to be
optimized.
Fructose-1,6-bisphosphate can only undergo the
reactions of glycolysis. The components of the
pathway up to this point can have other metabolic
fates.
The physiologically irreversible glycolytic steps
are those catalyzed by HK, PFK and PK. Thus, they
are controlling points in glycolysis.
46. Hexokinase is inhibited by glucose-6-phosphate.
Phosphofructokinase is inhibited by ATP and citrate.
Pyruvate kinase is inhibited is inhibited by ATP,
acetylCoA and alanine.
Phosphofructokinase is stimulated by AMP and
fructose-2,6-bisphosphate.
Pyruvate kinase is stimulated by AMP and fructose-
1,6-bisphosphate.
An isomerase is a general term for an enzyme that
changes the form of a substrate without changing
its empirical formula.
A mutase is an enzyme that moves a functional
group such as a phosphate to a new location in a
substrate molecule.
47. The glucokinase has a higher Km for glucose than
hexokinase. Thus, under conditions of low glucose,
the liver will not convert glucose to glucose-6-
phosphate, using a substrate that is needed
elsewhere. When the glucose concentration becomes
higher, however, glucokinase will function to help
phosphorylate glucose so that it can be stored as
glycogen.
The net yield of ATP from glycolysis is the same, 2
ATP, when either fructose, mannose, and
galactose is used. The energetics of the conversion
of hexoses to pyruvate are the same regardless of
hexose type.
The net yield of ATP is 3 from glucose derived from
glycogen because the starting material is glucose-1-
phosphate. One of the priming reactions is no longer
used.
48. A reaction with a negative ΔGo is
thermodynamically possible under standard
conditions.
Individuals who lack the gene that directs the
synthesis of the M form of the enzyme PFK can
carry on glycolysis in their livers but suffer muscle
weakness because they lack the enzyme in muscle.
The reaction of 2-PG to PEP is a dehydration (loss of
water) rather than a redox reaction.
The hexokinase molecule changes shape
drastically on binding to substrate, consistent with
the induced fit theory of an enzyme adapting itself to
its substrate.
49. ATP is an inhibitor of several steps of glycolysis as
well as other catabolic pathways. The purpose of
catabolic pathways is to produce energy, and high
levels of ATP mean the cell already has sufficient
energy. G-6-P inhibits HK and is an example of
product inhibition. If G-6-P level is high, it may
indicate that sufficient glucose is available from
glycogen breakdown or that the subsequent enzymatic
steps of glycolysis are going slowly. Either way there
is no reason to produce more G-6-P.
Phosphofructokinase is inhibited by a special
effector molecule, fructose-2,6-bisphosphate,
whose levels are controlled by hormones. It is also
inhibited by citrate, which indicates that there is
sufficient energy from the TCA cycle probably from fat
or amino acid catabolism.
50. PK is also inhibited by acetylCoA, the presence of
which indicates that fatty acids are being used to
generate energy for the citric acid cycle.
The main function of glycolysis is to feed carbon
units to the TCA cycle. When these carbon
skeletons can come from other sources, glycolysis is
inhibited to spare glucose for other purposes.
Thiamine pyrophosphate (TPP) is a coenzyme in the
transfer of 2-carbon units. It is required for catalysis by
pyruvate decarboxylase in alcoholic fermentation. The
important part of TPP is the five-membered ring where
a C is found between an S and N. This carbon forms a
carbanion and is extremely reactive, making it able to
perform nucleophilic attack on carbonyl groups
leading to decarboxylation of several compounds in
different pathways.
51. TPP is a coenzyme required in the reaction
catalyzed by pyruvate carboxylase. Because this
reaction is a part of the metabolism of ethanol, less
will be available to serve as a coenzyme in the
reactions of other enzymes that require it.
Animals that have been run to death have
accumulated large amounts of lactic acid in their
muscle tissue, accounting for the sour taste of their
meat.
Conversion of glucose to lactate rather than pyruvate
recycles NADH.
The formation of fructose-1,6-bisphosphate is the
committed step in glycolysis. It is also one of the
energy-requiring steps of the said pathway.
52. A positive ΔGo does not necessarily mean
that the reaction has a positive ΔG.
Substrate concentrations can make a
negative ΔG out of a positive ΔGo.
The entire pathway can be looked at as a
large coupled reaction. Thus, if the overall
pathway has a negative ΔG, an individual step
may be able to have a positive ΔG and the
pathway can still continue.
53. In glycogen storage, the reactions that require ATP are:
1. formation of UDP-glucose from glucose-1-phosphate
and UTP (indirect requirement since ATP is needed
to regenerate UTP) (UDP-glucose phosphorylase)
2. regeneration of UTP (nucleoside phosphate kinase)
3. carboxylation of pyruvate to oxaloacetate (pyruvate
carboxylase)
Reactions that produce ATP are NONE.
Three differences between NADPH and NADH
1. phosphate at 2’ position of ribose in NADPH
2. NADH is produced in oxidative reactions that yield ATP
while NADPH is a reducing agent in biosynthesis.
3. Different enzymes use NADH as a coenzyme compared
to those that require NADPH.
54. In glycogen storage, there is no reaction
that requires acetylCoA but biotin is
required in the carboxylation of pyruvate
to oxaloacetate.
The four fates of glucose-6-phosphate are:
Converted to glucose (gluconeogenesis)
Converted to glycogen (glycogenesis)
Converted to pentose phosphates
Hydrolyzed to pyruvate (glycolysis)
55. In making equal amounts of NADPH and pentose
phosphates, it only involves oxidative reactions. In making
mostly or purely NADPH, the use of oxidative reactions,
transketolase and transaldolase reactions, and
gluconeogenesis are required. In making mostly or only
pentose phosphates, needed reactions are transketolase,
transaldolase, and glycolysis in reverse.
Transketolase catalyzes the transfer of 2-carbon unit, whereas
transaldolase catalyzes the transfer of a 3-carbon unit.
It is essential that the mechanisms that activate glycogen
synthesis also deactivate glycogen phosphorylase because
they both occur in the same cell compartment. If both are on at
the same time, a futile ATP hydrolysis results. On/off
mechanism is highly efficient in its control.
56. UDPG, in glycogen biosynthesis, transfers glucose to
the growing glycogen molecule.
Glycogen synthase is subject to covalent
modification and to allosteric control. The enzyme is
active in its phosphorylated form and inactive when
dephosphorylated.
AMP is an allosteric inhibitor of glycogen synthase,
whereas ATP and glucose-6-phosphate are
allosteric activators.
In gluconeogenesis, biotin is the molecule to which
carbon dioxide is attached to the process of being
transferred to pyruvate. The reaction produces
oxaloacetate, which then undergoes further reactions
of gluconeogenesis. Biotin is not used in
glycogenesis and PPP.
57. In gluconeogenesis, glucose-6-phosphate is
dephosphorylated to glucose (last step); in glycolysis,
G-6-P isomerizes to fructose-6-phosphate (early step).
The Cori cycle is a pathway in which there is cycling of
glucose due to glycolysis in muscle and
gluconeogenesis in liver. The blood transports lactate
from muscle to liver and glucose from liver to muscle.
There is a net gain of 3, rather than 2, ATP when
glycogen, not glucose, is the starting material of
glycolysis.
58. Control mechanisms are important in metabolism.
They are:
Allosteric control (takes place in msec)
Covalent control (takes place from s to min)
Genetic control ( longer time scale)
Enzymes, like all catalysts, speed up the forward and
reverse reaction to the same extent. Having different
catalysts is the only way to ensure independent
control over the rates of the forward and the reverse
process.
The glycogen synthase is an exergonic reaction
overall because it is coupled to phosphate ester
hydrolysis.
59. Increasing the level of ATP is favorable to both
gluconeogenesis and glycogen synthesis.
Decreasing the level of fructose-1,6-bisphosphate
would tend to stimulate glycolysis, rather than
gluconeogenesis and glycogen synthesis.
If a cell needs NADPH, all the reactions of the PPP
take place. If a cell needs ribose-5-phosphate, the
oxidative portion of the pathway can be bypassed and
only the nonoxidative reshuffling reactions take place.
The PPP does not have a significant effect on the ATP
supply of a cell.
Glucose-6-phosphate is expectedly oxidized to a
lactone rather than an open-chain ester because the
latter is easy to hydrolyze.
60. In the PPP resshuffling reactions, without an
isomerase, all the sugars involved are keto
sugars that are not substrates for
transaldolase.
Sugar nucleotides (UDPG) have two
phosphates which when hydrolyzed drives
towards the polymerization of glycogen. Thus,
they are fit for glycogenesis.
