Carbohydrates, or carbs, are sugar molecules. Along with proteins and fats, carbohydrates are one of three main nutrients found in foods and drinks. Your body breaks down carbohydrates into glucose. Glucose, or blood sugar, is the main source of energy for your body's cells, tissues, and organs
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Biochemistry of carbohydrates_prepared_by_Drx_Raju_Yadav_2021
1. CARBOHYDRATE
Prepared By:
Asst Prof. Mr. Raju Yadav.Asst Prof. Mr. Raju Yadav.
M.S. Pharm (NIPER)
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2. ďCarbohydrates are polyhydroxy, aldehydes or ketones, or
substances that yield such compounds on hydrolysis.
ďMany, but not all, carbohydrates have the empirical formula
(CH2O)n, [nâĽ3]; some also contain nitrogen, phosphorus, or sulfur.(CH2O)n, [nâĽ3]; some also contain nitrogen, phosphorus, or sulfur.
ďCarbohydrate literally means, hydrates of carbonâ.
ďCarbohydrates are the most abundant biomolecules on Earth.
3. ⢠Certain carbohydrates (sugar and starch) are a dietary staple. Most abundant dietary source of
energy (4 cal/g)
⢠Insoluble carbohydrate polymers serve as structural and protective elements:
⢠in the cell walls of bacteria and plants
⢠in the connective tissues of animals
⢠lubricate skeletal joints
⢠participate in recognition and adhesion between cells
⢠Complex carbohydrate polymers that are covalently attached to proteins or lipids are called
glycoconjugates.
⢠act as signals that determine the intracellular location or metabolic fate of these hybrid
molecules
⢠Carbohydrates are precursors of many organic molecules (fats, amino acids, etc.)
⢠They serve as storage form of energy (Ex- Glycogen, Starch)
4. ⢠The word âsaccharideâ is derived from the Greek âsakcharonâ, meaning âsugarâ
⢠Monosaccharides (simple sugars):
⢠Consist of a single polyhydroxy aldehyde or ketone unit.
⢠Oligosaccharides:
⢠consist of short chains of monosaccharide units, or residues (2-10), joined by
characteristic
linkages called glycosidic bonds.linkages called glycosidic bonds.
⢠Disaccharides:
⢠Consists of two monosaccharide units joined by glycosidic bond
⢠Ex- Sucrose (Glucose + Sucrose)
⢠Polysaccharides:
⢠sugar polymers containing more than 20 or so monosaccharide units, and some have
hundreds or thousands of units
⢠Ex- Cellulose, Glycogen
5. ď Simplest carbohydrates that can not be hydrolyzed to smaller
carbohydrates.
ď General chemical formula of unmodified monosaccharide is (C.H2O)n
where nâĽ3
ď Consist of a single polyhydroxy aldehyde or ketone unit.ď Consist of a single polyhydroxy aldehyde or ketone unit.
ď The most abundant monosaccharide in nature is the six-carbon sugar D-
glucose.
ď Monosaccharides of more than four carbons tend to have cyclic structures.
ď Ex- Glyceraldehyde, Glucose, fructose, etc.
6. ⢠Classified according to 3 different
characteristics:characteristics:
⢠Placement of its carbonyl group
⢠Number of carbon atoms present
⢠Chiral handedness
7. ⢠Classes based on placement of its carbonyl group:
⢠ALDOSE: Functional group is an aldehyde group (-CHO)
⢠Ex- Glyceraldehyde, Glucose, etc
⢠KETOSE: Functional group is a keto group (>C=O)
⢠Ex- Dihydroxyacetone, Fructose, etc.
8. ⢠Classes based on number of carbon
atomspresent:
⢠Triose (3 C)
⢠Tetrose (4 C)
⢠Pentose (5 C)
⢠Hexose (6 C)⢠Hexose (6 C)
⢠Heptose (7 C)
9.
10.
11. o Stereoisomers: Compounds that have same structural formulae but differ in their
spatial configuration.
o A carbon is said to be asymmetric (chiral) when it is attached to four different atoms or
groups.
o The number of asymmetric carbon atoms (n) determines the possible isomers of a
given compound which is equal to 2n.
o Stereoisomerism is a characteristic feature of all sugars except Dihydroxyacetone.
o Example-
Glucose has 4 asymmetric carbon atoms. No. of isomers = 24 = 16
Glyceraldehyde has 1 asymmetric carbon atom. No. of isomers = 21 = 2
Dihydroxyacetone has no asymmetric carbon atoms. Hence, no isomer is
possible.
12. ⢠Classes based on chiral handedness:
⢠D and L isomers: Assignment of D or L isomer is
made according to the orientation of the asymmetric
carbon atom furthest from the carbonyl group.
⢠In a standard Fischer projection if the hydroxyl group
is on the right, the molecule is D sugar, and if theis on the right, the molecule is D sugar, and if the
hydroxyl group is on the left, the molecule is L sugar.
⢠D-sugars are biologically more common.
13. ⢠Optical activity of sugars:
⢠It is the characteristic feature of compounds with asymmetric carbon atoms.
When a beam of polarized light is passed through a solution of an optical
isomer, it will be rotated to either the right or left.
⢠The terms dextrorotatory (+) and levorotarory (-) are used to compounds that
respectively rotate the plane of polarized light to the right or to the left.
⢠It may be noted that the D and L configurations of sugars are primarily
based on the
structure, optical activities may be different.
⢠Racemic mixture: If D and L isomers are present in equal concentration, it is
known as racemic mixture or DL mixture. Racemic mixture does not exhibit any
optical activity, since the dextro- and levorotatory activities cancel each other.
14. ⢠Epimers
⢠If two monosaccharides differ from each other in their configuration around a single
specific carbon (other than anomeric carbon), they are referred to as epimers to each
other.
⢠D-glucose and D-mannose differ only in the stereochemistry at C-2, are epimers.
⢠D-glucose and D-galactose which differ at C-4, are epimers.
Inter-conversions of epimers (eg.-
glucose to galactose and vice versa)
is known as epimerization and is
catalyzed by a group of enzymes
called epimerases
15. ⢠In aqueous solution, aldotetroses and all monosaccharides with five or
more carbon atoms in the backbone occur predominantly as cyclic (ring)
structures in which the carbonyl group has formed a covalent bond with the
oxygen of a hydroxyl group along the chain.
⢠The formation of these ring structures is the result of a general reaction
between alcohols and aldehydes or ketones to form derivatives called
hemiacetals or hemiketals.
⢠These structures contain an additional asymmetric carbon atom and thus
can exist in two stereoisomeric forms.
16. ⢠D-glucose exists in solution as an intramolecular hemiacetal in which the
free hydroxyl group at C-5 has reacted with the aldehydic C-1, rendering the
latter carbon asymmetric and producing two stereoisomers, designated as Îą
and β.
⢠These six-membered ring compounds are called pyranoses because they
resemble the six membered ring compound pyran.
⢠The systematic names for the two ring forms of D-glucose are ι-D-
glucopyranose and β-D- glucopyranose.glucopyranose and β-D- glucopyranose.
⢠Only aldoses having five or more carbon atoms can form pyranose rings.
17. ⢠Aldohexoses also exist in cyclic forms having five membered rings,
which, because they resemble the five membered ring compound furan,
are called furanoses.
⢠The six-membered aldopyranose ring is much more stable than the
aldofuranose ring and predominates in aldohexose solutions.
18. Anomers
⢠Isomeric forms of monosaccharides that differ only in their configuration about the
hemiacetal or hemiketal carbon atom are called anomers.
⢠The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon.
⢠In case of Îą-anomer, the âOH group held by anomeric carbon is on the opposite side of
the
âCH2OH group of the sugar ring. The opposite is true for β-anomers.
⢠The ι- and β-anomers of D-glucose interconvert in aqueous solution by a process called⢠The ι- and β-anomers of D-glucose interconvert in aqueous solution by a process called
mutarotation.
⢠Thus, a solution of ι-D-glucose and a solution of β-D-glucose eventually form identical
equilibrium mixtures having identical optical properties. This mixture consists of about
one-third ι-D-glucose (36%), two-thirds β-D-glucose (63%), and very small amounts of
the linear and five-membered ring (glucofuranose) forms (1%).
ι-D-glucose Equilibrium mixture β-D-
glucose
+112.2° +52.7° +18.7°
19. ⢠Ketohexoses also occur in ι and β anomeric forms.
⢠In these compounds the hydroxyl group at C-5 (or C-6)
reacts with the keto group at C-2, forming a furanose (or
pyranose) ring containing a hemiketal linkage.
⢠D-Fructose readily forms the furanose ring, the more⢠D-Fructose readily forms the furanose ring, the more
common anomer of this
sugar in combined forms or in derivatives is D-
fructofuranose.
⢠The specific optical rotation of fructose is -92° at
equilibrium.
20. ⢠Monosaccharides can be oxidized by relatively mild
oxidizing agents such as ferric (Fe3+) or cupric (Cu2+).
⢠The carbonyl carbon is oxidized to a carboxyl group.
⢠Sugars capable of reducing ferric or cupric ion are called
reducing sugars. They have free aldehyde or ketone group
present in their structure.
⢠Ex- Glucose
⢠Sugars not capable of reducing ferric or cupric ion are
called non-reducing sugars. They do not have free
aldehyde or ketone group present in their structure.
⢠Ex- Sucrose
⢠This property is the basis of Fehlingâs reaction, a qualitative
test
for the presence of reducing sugar.
21. There are a number of sugar
derivatives in which a hydroxyl
group in the parent compound
is replaced with another
substituent, or a carbon atom
is oxidized to a carboxyl
group.group.
⢠In amino sugars, an âNH2
group replaces one of the -OH
groups in the parent
⢠hexose.
⢠Substitution of âH for â
OH produces a deoxy sugar.
⢠The acidic sugars contain a
carboxylate group, which
confers a negative charge at
neutralpH.
22. ⢠Sugar acids: Oxidation of aldehyde or primary alcohol groups in
the monosaccharide results in sugar acids.
⢠The acidic sugars contain a carboxylate group, which confers a negative
charge at
neutral pH.
⢠Examples:
⢠Gluconic acid is produced from glucose by oxidation of aldehyde group.
⢠Glucuronic acid is formed from glucose by oxidation of primary alcohol group (C6).
23. ⢠Amino sugars: When one or more hydroxyl groups of the monosaccharide
are replaced by amino groups, the products formed are called amino sugars.
⢠They are present as constituents of heteropolysaccharides.
⢠Examples:
⢠D-glucosamine
⢠D-galactosamine
⢠They are sometimes acetylated.
⢠Examples:
⢠N-acetyl-D-glucosamine
24. ⢠Deoxysugars: They contain one oxygen less than that of their parent
molecule.
⢠The groups âCHOH and âCH2OH become âCH2 and âCH3 due to absence of
one oxygen atom.
⢠Examples:
⢠D-2-Deoxyribose
⢠L-Rhamnose
⢠L-Fucose
25. ⢠Sugar alcohols: Sugar alcohols (polyols) are produced by reduction of
aldoses or
ketoses.
⢠Examples:
⢠Sorbitol from glucose
⢠Mannitol from mannose⢠Mannitol from mannose
⢠Alditols: The monosaccharides on reduction yield polyhydroxy alcohols
known as alditols.
⢠Examples:
⢠Ribitol (constituent of flavin coenzymes)
⢠Glycerol (Component of lipid)
⢠Xylitol (Sweetener used in sugarless gums and candies)
26. ⢠Disaccharides consist of two monosaccharides
joined covalently by an O-glycosidic bond,
which is formed when a hydroxyl group of one
sugar reacts with the anomeric carbon of the
other.
⢠Example: maltose, lactose, and sucrose
⢠Glycosidic bonds are readily hydrolyzed by acid
but resist cleavage by base. Thus disaccharidesbut resist cleavage by base. Thus disaccharides
can be hydrolyzed to yield their free
monosaccharide components by boiling with
dilute acid.
⢠N-glycosyl bonds join the anomeric carbon of a
sugar to a nitrogen atom in glycoproteins and
nucleotides.
⢠General formula: Cn(H2O)n-1
27. ⢠The oxidation of a sugarâs anomeric carbon by cupric or ferric ion (the
reaction that defines a reducing sugar) occurs only with the linear
form, which exists in equilibrium with the cyclic form(s).
⢠When the anomeric carbon is involved in a glycosidic bond, that
sugar residue cannot
take the linear form and therefore becomes a non-reducing sugar.take the linear form and therefore becomes a non-reducing sugar.
⢠The end of a chain with a free anomeric carbon (one not involved in a
glycosidic bond) is commonly called the reducing end.
28. ⢠The disaccharide maltose
contains two D-glucose
residues joined by a
glycosidic linkage between C-
1 (the anomeric carbon) of
one glucose residue and C-4
of the other.
⢠Because the disaccharide
retains a free anomeric
carbon (C-1 of the glucose
residue on the right), maltose
is a reducing sugar.
29. ⢠By convention, the name describes the compound with its nonreducing end to the left.
⢠Give the configuration (ι or β) at the anomeric carbon joining the first monosaccharide unit (on
the left) to the second.
⢠Name the nonreducing residue; to distinguish five- and six-membered ring structures, insert
âfuranoâ or âpyranoâ into the name.
⢠Indicate in parentheses the two carbon atoms joined by the glycosidic bond, with an arrow
connecting the two numbers; for example, (1 4) shows that C-1 of the first-named sugar
residue is joined to C-4 of the second.
⢠Name the second residue.
⢠If there is a third residue, describe the second glycosidic bond by the same conventions.
Short name:
Glc(Îą1 4)Glc
30.
31. Inversion of sucrose:
⢠Sucrose is dextrorotatory (+66.5°). But when hydrolyzed, it becomes
levorotatory (- 28.2°). The process of change in optical rotation from
dextrorotatory(+) to levorotatory (-) is referred to as inversion. The
hydrolyzed mixture of sucrose, containing glucose and fructose, is known as
invert sugar.
⢠Hydrolysis of sucrose by sucrase or dilute acid yeilds one molecule of glucose
and one molecule of fructose.
⢠Sucrose first splits into ι-D-glucopyranose (+) and β-D-fructofuranose (+). But
β-D- fructofuranose is less stable and gets converted into β-D-fructopyranose
(-). The overall effect in the mixture becomes levorotatory (-).
32.
33.
34.
35. ⢠Carbohydrates containing repeating units (more than 10 units) of the
monosaccharides or their derivatives linked by glycosidic linkages are called
polysaccharides.
⢠They are primarily concerned with 2 important functions:
⢠Structural role
⢠Storage of energy⢠Storage of energy
⢠Polysaccharides can be linear or branched. The occurrence of branched
polysaccharides is due to the fact that glycosidic linkages can be formed at any one
of the âOH groups of a monosaccharide.
⢠Polysaccharides are of high molecular weight. They are usually tasteless (non-
sugars) and
form colloids with water.
36. Polysaccharides are of two types:
⢠Homopolysaccharides (Homoglycans):
They, on hydrolysis, yield only one type of
monosaccharide. They are named based
on the nature of the monosaccharide unit.
Example: Glucan (polymer of
glucose), Fructosan (polymer of
fructose)fructose)
⢠Heteropolysaccharides (heteroglycans):
They, on hydrolysis, yield a mixture of a
few types of monosaccharide units or their
derivatives.
Example: Peptidoglycan (polymer of
N- acetylglucosamine and N-
acetylmuramic acid residues)
37.
38. Dextrins
⢠These are the breakdown products of starch by the enzyme amylase or dilute
acids.
⢠Starch is hydrolyzed through different dextrins and finally to maltose and
glucose.
⢠The various intermediates (identified by iodine coloration) are soluble starch
(blue), amylodextrin (violet), erythrodextrin (red) and achrodextrin (no colour).
Inulin
⢠Inulin is a polymer of fructose.
⢠It occurs in dahlia bulbs, garlic, onion, etc.
⢠It is a low molecular weight (~ 5000) polysaccharide easily soluble in water.
⢠Inulin is not utilized by the body.
⢠It is used for assessing kidney function through measurement of glomerular
filtration rate (CFR).
39. ⢠Cellulose occurs extensively in plants and is totally absent in animals.
⢠Cellulose is composed of β-D-glucose units linked by β(1 4) glycosidic bonds.
⢠Cellulose can not be digested by mammals due to lack of the enzyme that cleaves β-
glycosidic bonds. Hydrolysis of cellulose yields a disaccharide, cellobiose, which is
further broken down to β-D-glucose units.
⢠It is a major constituent of fibers, the non-digestible carbohydrate.⢠It is a major constituent of fibers, the non-digestible carbohydrate.
40.
41. ⢠Chitin is a linear homopolysaccharide composed of N-acetylglucosamine
residues in β linkage.
⢠The only chemical difference from cellulose is the replacement of the
hydroxyl group at C-2 with an acetylated amino group.
42. ⢠The rigid component of bacterial cell walls is a heteropolymer of
alternating (β1 4)-linked N-acetylglucosamine and N-acetylmuramic
acid residues.
⢠The enzyme lysozyme kills bacteria by hydrolyzing the (β1 4) glycosidic
bond between N-bond between N-
acetylglucosamine and Nacetylmuramic acid.
43. ď Main source of energy in the body. Energy
production from carbohydrates will be 4 k
calories/g (16 k Joules/g).
ď Storage form of energy (starch and glycogen).
ď Excess carbohydrate is converted to fat.
FUNCTIONS OF CARBOHYDRATES
ď Excess carbohydrate is converted to fat.
ď Glycoproteins and glycolipids are components of
cell membranes and receptors.
ď Structural basis of many organisms. For example,
cellulose of plants,exoskeleton of insects etc.
44. ⢠Glucose is a major carbohydrate
⢠It is a major fuel of tissues
⢠It is converted into other carbohydrates
ďź Glycogen for storage.
ďź Ribose in nucleic acids.
Biomedical Importance Of Glucose
ďź Ribose in nucleic acids.
ďź Galactose in lactose of milk.
ďź They form glycoproteins & proteoglycans
ďź They are present in some lipoproteins (LDL) .
ďź Present in plasma membrane:glycocalyx.
ďź Glycophorin is a major intergral membrane glycoprotein
of human erythrocytes.
45. Thousands of chemical reactions
are taking place inside a cell in
an organized, well co-ordinated
and purposeful manner; all these
reactions are called as
METABOLISM.
TYPES OFMETABOLIC PATHWAY:
Metabolism
TYPES OFMETABOLIC PATHWAY:
ďźCatabolic Pathway
ďźAnabolic Pathway
ďźAmphibolic Pathway
STAGES AND PHASES
OFMETABOLISM:
ďźPrimary
ďźSecondary
ďźTertiary
49. 1) Insulin-independent transport system of glucose: Not dependent on
hormone insulin. This is operative in â hepatocytes, erythrocytes (GLUT-1)
and brain.
2) Insulin-dependent transport system: Muscles and adipose tissue (GLUT-4).
Type 2 diabetes melitus:
-Due to reduction in the-Due to reduction in the
quantity of GLUT-4 in insulin
deficiency.
-Insuin resistance is observed
in tissues.
51. 1) Takes place in all cells of the body.
2) Enzymes present in âcytosomal fractionâ of the cell.
3) Lactate â end product â anaerobic condition.
4) Pyruvate(finally oxidized to CO2 & H2O) â end
product of aerobic condition.
Salient features:
5) Tissues lacking mitochondria â major pathway âATP
synthesis.
6) Very essential for brain â dependent on glucose for
energy.
7) Central metabolic pathway
8) Reversal of glycolysis â results in gluconeogenesis.
52. Reactions of Glycolysis
1) Energy Investment phase (or)
priming phasepriming phase
2) Splitting phase
3) Energy generation phase
53. ď§Glucose is phosphorylated to glucose-6-phosphate by hexokinase (or) glucokinase.
ď§Glucose-6-phosphate undergoes isomerization to give fructose -6- phosphate in the
presenseof phospho-hexose isomerase and Mg2+
ď§Fructose-6-phosphate is phoshorylated to fructose 1,6-bisphosphate by
phosphofructokinase
Energy
Investment
Phase
⢠Fructose 1,6-bisphosphate ď glyceraldehyde 3-phosphate + dihydroxyacetone
phosphate.(aldolase enzyme)
⢠2 molecules of glyceraldehyde 3-phosphate are obtained from 1 molecule of glucoseSplitting
PhasePhase
⢠Glyceraldehyde 3-phosphate ď 1,3-bisphosphoglycerate(glyceraldehyde 3-phosphate
hydrogenase )
⢠1,3-bisphosphoglycerate ď 3-phosphoglycerate (phosphoglyceratekinase)
⢠3-phosphoglycerate ď 2-phosphoglycerate (phosphoglycerate mutase)
⢠2-phosphoglycerate ď phosphoenol pyruvate (enolase + Mg2+ &Mn2+)
⢠Phosphoenol pyruvate ď pyruvate [enol] (pyruvate kinase ) ď pyruvate [keto] ď L-
Lactate
(lactate dehydrogenase)
Energy
Generation
Phase
54.
55.
56. ATPproduced ATPutilized Net energy
In absence
of oxygen
(anaerobic
glycolysis)
4ATP
(Substrate level
phosphorylation)
2ATP from 1,3 DPG.
2ATP fromphosphoenol pyruvate
2ATP
From glucose to glucose -
6-p.
From fructose -6-p to
fructose 1,6 p.
2ATP
In presence
of oxygen
4ATP
(substrate level
2ATP
-From glucose to glucose-
8 ATP/
6 ATP(Pyruvate
ATPproduction = ATPproduced - ATPutilized
Energy production of glycolysis:
of oxygen
(aerobic
glycolysis)
(substrate level
phosphorylation)
2ATP from 1,3 BPG.
2ATP fromphosphoenol
pyruvate.
-From glucose to glucose-
6-p.
From fructose -6-p to
fructose 1,6 p.
6 ATP(Pyruvate
dehydrogenase
2NADH,ETC,
Oxidative
phosphorylation)
+ 4ATP or6ATP
(from oxidation of2 NADH +
H in
mitochondria).
57. CLINICALASPECT
1) Lactic acidosis
ďź Normal value â 4 to 15 mg/dl.
ďź Mild forms â strenous exercise, shock, respiratory diseases,ďź Mild forms â strenous exercise, shock, respiratory diseases,
cancers
ďź Severe forms â Impairment/collapse of circulatory system â
myocardial infarction, pulmonary embolism, uncontrolled
hemmorrhage and severe shock.
58. 2) Cancer and glycolysis :
ď Cancer cells â increased uptake of glucose and
glycolysis.
ď Blood vessels unable to supply adequate oxygen âď Blood vessels unable to supply adequate oxygen â
HYPOXIC condition â Anaerobic glycolysis / hypoxic
glycolysis â Involvement of Hypoxic inducible
transcription factor (HIF).
ď Treatment : Use drugs that inhibit vascularization of
tumours
59. Pasteur effect :
ď Inhibition of glycolysis by oxygen
(Phosphofructokinase).
Crabtree effect :Crabtree effect :
ď The phenomenon of inhibition of oxygen
consumption by the addition of glucose to tissues
having high aerobic glycolysis.
60. ď Supplementary pathway/ Shunt pathway to glycolysis .
ď Erythrocytes
ď Synthesis of 2,3-bisphosphoglycerate (2,3-BPG).
RAPARPORT â LEUBERING CYCLE
ď Synthesis of 2,3-bisphosphoglycerate (2,3-BPG).
ď Without the synthesis of ATP.
ď Help to dissipate or waste the energy not needed by RBCs.
ď Supply more oxygen to the tissues.
61. CITRIC ACID CYCLE
KREBS CYCLE / TRICARBOXYLIC
ACID/ TCA CYCLE
ďEssentially involves the oxidation of acetyl CoA to CO2 andH2O.
ďThis Cycle utilizes about two-third of total oxygen
consumed by the body.
62. ⢠HansAdolf
Krebs
⢠1937
⢠Mitochondrial
matrix
⢠In close
⢠65-70% of the
ATPis
synthesized
⢠Name : TCA
Brief History:
Location of TCA Overview
⢠1937
⢠Studies of
oxygen
consumptiom
in pigeon
breast muscle.
⢠In close
proximity to
the electronic
transport
chain.
⢠Name : TCA
used because at
the ouset of the
cycle
tricarboxylic
acids participate.
63. 1) Formation of citrate : Condensation of acetyl CoA and
oxaloacetate ď catalysed by citrate synthase.
2) & 3) Citrate is isomerized to isocitrate ď aconitase (two steps).
Reactions of citric acid cycle
4) & 5) Formation of áž-ketoglutarate : enzyme isocitrate
dehydrogenase.
6) Conversion of áž-ketoglutarate to succinyl CoA : through
oxidative decarboxylation, catalysed by áž- ketoglutarate
dehydrogenase complex.
64. 7) Formation of succinate : enzyme succinate thiokinase
GTP +ADP ď ď ATP+ GDP (nucleoside diphosphate
kinase)
8) Conversion of succinate to fumarase : enzyme succinate
dehydrogenasedehydrogenase
9)Formation of malate : enzyme fumarase 10)Conversion of
malate to oxaloacetate : enzyme malate dehydrogenase.
65.
66. ⢠TCA cycle is strictly aerobic in contrast to glycolysis.
⢠Total of 12 ATPare produced from one acetyl CoA:-
ďź During the process of oxidation of acetyl CoA viacitric acid
cycle ď 3 NADH & 1 FADH2.
ďź Oxidation of 3 NADH by electron transport chain
coupled with oxidative phosphorylation results in 9 ATP,
FADH2 ď 2ATP.
ďź One substrate level phosphorylation.
67. APPLIED ASPECTS OF
TCACYCLE
ďMitochondrial encephalopathy occurs due to
fumarase deficiency.
ďIt is a mitochondrial myopathy affecting both theďIt is a mitochondrial myopathy affecting both the
skeletal muscles and brain.
68. GLUCONEOGENESIS
ďThe synthesis of glucose from non-carbohydrate
compounds is known as gluconeogenesis.
ďMajor substrate/precursors : lactate, pyruvate, glycogenic
amino acids, propionate & glycerol.
ďMajor substrate/precursors : lactate, pyruvate, glycogenic
amino acids, propionate & glycerol.
ďTakes place in liver (1kg glucose) ; kidney matrix( 1/3rd).
ďOccurs in cytosol and some produced in mitochondria.
69. Importance of Gluconeogenesis
Under anaerobic
condition, glucose is
the only source to
supply skeletal
muscles.
Brain,CNS,
erythrocytes,testes
and kidney medulla
dependent on
glucose for cont.
supply of energy.
Occurs to meet the
basal req of the
body for glucose in
fasting for even
more than a day
Effectively
clears,certain
metabolites
produced in the
tissues that
accumulates in
blood
supply of energy.
71. The cycle involveing the synthesis of
glucose in liver from the skeletal muscle
Cori Cycle
glucose in liver from the skeletal muscle
lactate and the reuse of glucose thus
synthesized by the muscle for energy
purpose is known as Cori cycle.
73. * Glucagon stimulates gluconeogenesis:
1)Active pyruvate kinase converted to inactiveform
2)Reduces the concentration of fructose 2,6-bisphosphate.
* Glycogenic amino acids have stimulating influence on gluconeogenesis.
* Diabetes mellitus where amino acids are mobilized from muscle protein for the
purpose of gluconeogenesis.
ClinicalAspects
Acetyl CoA promotesgluconeogenesis:
* During starvation â due to excessive lipolysis in adipose tissue âacetyl CoA
accumulates in the liver.
*Acetyl CoA allosterically activates pyruvate carboxylase resulting in enhanced glucose
production
*Alcohol inhibits gluconeogenesis
74. ďźGlycogen is a storage form of glucose in animals.
ďźStored mostly in liver (6-8%) and muscle (1-2%)
ďźDue to muscle mass the quantity of glycogen in muscle = 250g
GLYCOGEN METABOLISM
ďźDue to muscle mass the quantity of glycogen in muscle = 250g
and liver =75g
ďźStored as granules in the cytosol.
ďźFunctions : Liver glycogen â maintain the blood glucose level
Muscle glycogen â serves as fuel reserve
75. ďą Synthesis of glycogen from glucose.
ďą Takes place in cytosol.
ďą Requires UTP and ATPbesidesglucose.
GLYCOGENESIS
ďą Requires UTP and ATPbesidesglucose.
ďą Steps in synthesis :
1) Synthesis of UDP- glucose
2) Requirement of primer to initiate glycogenesis
3) Glycogen synthesis by glycogen synthase
4) Formation of branches in glycogen
76.
77. ďąDegradation of stored glycogen in liver and muscle constitutes
glycogenolysis.
ďą Irreversible pathway takes place in cytosol.
ďą Hormonal effect on glycogen metabolism :
1) Elevated glucagon â increases glycogen degradation
GLYCOGENOLYSIS
1) Elevated glucagon â increases glycogen degradation
2) Elevated insulin â increases glycogen synthesis
ďą Degraded by breaking majorly Îą-1,4- and Îą-1,6-glycosidicbonds.
ďą Steps in glycogenolysis:
1) Action of glycogen phosphorylase
2) Action of debranching enzyme
3) Formation of glucose-6-phosphate and glucose
78.
79. GLYCOGEN STORAGE DISEASES
TYPE ENZYME
DEFECTS
CLINICAL FEATURES
Type I (Von Gierkeâs
disease)
Glucose-6- phosphatase
deficiency.
Hypoglycemia, enlarged liver and kidneys,
gastro-intestinal symptoms, Nose bleed,
short stature, gout
Type II (Pompeâs
disease)
Acid maltase
deficiency
Diminished muscle tone, heart failure,
enlarged
tonguetongue
Type III (Coriâs
disease,Forbe disease
Debranching enzyme
deficiency
Hypoglycemia, enlarged liver, cirrhosis,
muscle weakness, cardiac involvement
Type IV (Andersenâs
disease)
Branching enzyme
deficiency
Enlarged liver & spleen, cirrhosis,
diminished muscle tone, possible nervous
system involvement
Type V (Mcardleâs
disease)
Muscle phosphorylase
deficiency
Muscle weakness, fatigue and muscle
cramps
80. TYPE ENZYME
DEFECTS
CLINICAL FEATURES
Type VI (Herâs
disease)
Liver phosphorylase
deficiency
Mild hypoglycemia, enlarged liver,
short stature in childhood
Type VII (Taruiâs
disease)
Phosphofructokinase
deficiency
Muscle pain, weakness and
decreased endurancedisease) deficiency decreased endurance
TypeVIII Liver phosphorylase
kinase
Mild hypoglycemia, enlarged liver,
short stature in childhood, possible
muscle weakness and cramps
Type 0 Liver glycogen
synthetase
Hypoglycemia, possible liver
enlargement
84. ďThis is an alternative pathway to glycolysis and TCA cycle
for the oxidation of glucose.
ďAnabolic in nature, since it is concerned with the
biosynthesis of NADPH and pentoses.
ďUnique multifunctional pathway
ďEnzymes located â cytosol
ďTissues active â liver, adipose tissue, adrenal gland,
erythrocytes, testes and lactating mammary gland.
86. ⢠Pentose or its derivatives are useful for the
synthesis of nucleic acids and nucleotides.
⢠NADPH is required :
-For reductive biosynthesis of fatty acids and
steroids.steroids.
- For the synthesis of certain amino acids.
- Anti-oxidant reaction
- Hydroxylation reactionâ detoxification of drugs.
- Phagocytosis
- Preserve the integrity of RBC membrane.
87. ⢠Pentose or its derivatives are useful for the
synthesis of nucleic acids and nucleotides.
⢠NADPH is required :
-For reductive biosynthesis of fatty acids and
steroids.
Significance of HMP Shunt
steroids.
- For the synthesis of certain amino acids.
- Anti-oxidant reaction
- Hydroxylation reactionâ detoxification of drugs.
- Phagocytosis
- Preserve the integrity of RBC membrane.
91. ďź Alternative oxidative pathway for glucose.
ďź synthesis of glucorinc acid,pentoses and vitamin (ascorbic acid).
ďź Normal carbohydrate metabolism ,phosphate esters are
involved â but in uronic acid pathway free sugars and sugar
acids are involved.acids are involved.
ďź Steps of reactions :
1) Formation of UDP-glucoronate
2) Conversion of UDP- glucoronate to L-gulonate
3) Synthesis of ascorbic acid in some animals
4) Oxidation of L-gulonate
92.
93. ⢠Effects of drugs : increases the pathway to achieve more
synthesis of glucaronate from glucose .
- barbital,chloro-butanol etc.
⢠Essential pentosuria : deficiency of xylitol-
Clinical Aspects
⢠Essential pentosuria : deficiency of xylitol-
dehydrogenase
- Rare genetic disorder
- Asymptomatic
- Excrete large amount of L-xylulose in urine
- No ill-effects
95. ďź Disaccharide lactose present in milk â principle source of of galactose.
ďź Lactase of intestinal mucosal cells hydrolyses lactose to galactose and glucose.
ďźWithin cell galactose is produced by lysosomal degradation of glycoproteins
and glycolipids.
ďź CLINICAL ASPECTS :
- Classical galactosemia : deficiency of galactose-1-phosphate- Classical galactosemia : deficiency of galactose-1-phosphate
uridyltransferase. Increase in galactose level.
- Galactokinase deficiency : Responsible for galactosemia and galactosuria.
- Clinical symptoms : loss of weight in infants, hepatosplenomegaly,jaundice,
mental retardation , cataract etc.
- Treatment : removal of galactose and lactose from diet.
96. Sorbitol/Polyol Pathway:
ďź Conversion of glucose to fructose via sorbitol.
ďź Glucose to Sorbitol reduction by enzyme aldolase (NADPH).
ďźSorbitol is then oxidized to fructose by sorbitol dehydrogenase and
NAD+.
METABOLISM OF FRUCTOSE
NAD+.
ďźFructose is preferred carbohydrate for energy needs of spermcells
due to the presence of sorbitol pathway.
ďźPathway is absent in liver.
ďźDirectly related to glucose : higher in uncontrolleddiabetes.
97. ďWhen the hydroxyl group of the sugar is replaced by theamino
group, the resultant compound is an amino sugar.
ďEg. Glucosamine,galactosamine,mannosamine,sialic acid etc.
ďEssential components of glycoproteins, glycosaminoglycans,
METABOLISM OF AMINO SUGARS
ďEssential components of glycoproteins, glycosaminoglycans,
glycolipids.
ďFound in some antibiotics.
ď20% of glucose utilized for the synthesis of amino sugars â
connective tissues.
98. ⢠Electron transport chain is a series of protein complexes
located in the inner membrane of mitochondria .
Electron transport chain reactions
101. ⢠Structural components of extracellular matrix.
⢠Act as sieves in extracellular matrix.
⢠Facilitate cell migration.
Functions of glycoaminoglycans
⢠Corneal transparency.
⢠Anticoagulant (Heparin).
⢠Components of synaptic & other vesicles.
102. MPS Defect Symptoms
MPS I (Hurler
syndrome)
Alpha-L-Iduronidase Mental retardation, micrognathia, coarse facial
features, macroglossia, retinal degeneration, corneal
clouding, cardiomyopathy, hepatosplenomegaly
MPS II (Hunter
syndrome)
Iduronate sulfatase Mental retardation (similar, but milder,
symptoms to MPS I). This type exceptionally
Mucopolysaccharidoses
syndrome) symptoms to MPS I). This type exceptionally
has X-linked recessive inheritance
MPS IIIA
(SanfilippoA)
Heparan sulfate N
sulfatase
Developmental delay, severe hyperactivity,
spasticity, motor dysfunction, death by the
second decade
MPS IIIB
(Sanfilippo B)
Alpha-
Acetylglucosaminidase
MPS IIIC
(Sanfilippo C)
Acetyl transferase
103. MPS Defect Symptoms
MPS IVA
(MorquioA)
Galactose-6-
sulfatase
Severe skeletal dysplasia, short stature,
motor dysfunction
MPS IVB (Morquio
B)
Beta
galactosidase
MPS VI (Maroteaux
Lamy
syndrome)
N acetylgalacto
samine 4 sulfatase
Severe skeletal dysplasia, short stature,
motor
syndrome)
MPS VII (Sly) Beta
glucoronidase
Hepatomegaly, skeletal dysplasia, short
stature, corneal clouding, developmental
delay
MPS IX (Natowicz
syndrome)
Hyaluronidase
deficiency
Nodular soft-tissue masses around joints,
episodes of painful swelling of the
masses, short-term pain, mild facial
changes, short stature, normal joint
movement, normal intelligence
104. ⢠Short and broad mandible
â˘Localized radiolucent lesions of
the jaw
â˘Flattened temporomandibular joints
Hunterâs syndrome
⢠Macroglossia
⢠Conical peg-shaped teeth
with generalized wide spacing
â˘Highly arched palated with flattened
alveolar ridges
⢠Hyperplastic gingiva
105. ROLE OF HORMONES IN
CARBOHYDRATE METABOLISM
⢠Postabsorptive state: Blood glucose is 4.5- 5.5mmol/L.
Regulation of Blood glucose
⢠Postabsorptive state: Blood glucose is 4.5- 5.5mmol/L.
⢠After carbohydrate meal: 6.5-7.2mmol/L
⢠During fasting : 3.3-3.9mmol/L
106. Maintenance of stable
levels of glucose in
blood is by
Metabolic & hormonal mechanisms
regulate blood glucose level
blood is by
ďź Liver.
ďź Extrahepatic tissues.
ďź Hormones .
109. ďś Hypothyroid
ď Fasting blood glucose is
lowered.
ďś Hyperthyroid
ďź It stimulates glycogenolysis & gluconeogenesis.
Role of thyroid hormone
lowered.
ď Patients have decreased
ability to utilise glucose.
ď Patients are less sensitive to
insulin than normal or
hyperthyroid patients.
ďś Hyperthyroid
ďś Fasting blood glucose is
elevated
ďś Patients utilise glucose at
normal or increased rate
110. Glucocorticoids
ďź Glucocorticoids are antagonistic to insulin.
ďź Inhibit the utilisation of glucose in extrahepatic tissues.
ďź Increased gluconeogenesis .
Epinephrine
ďź Secreted by adrenal medulla.ďź Secreted by adrenal medulla.
ďź It stimulates glycogenolysis in liver & muscle.
ďź It diminishes the release of insulin from pancreas.
Other Hormones
Anterior pituitary hormones:
Example- Growth hormone
111. Growth hormone:
ďź Elevates blood glucose level & antagonizes action of insulin.
ďź Growth hormone is stimulated by hypoglycemia (decreases
glucose uptake in tissues)
ďź Chronic administration of growth hormone leads to diabetesďź Chronic administration of growth hormone leads to diabetes
due to B cell exhaustion.
SEX HORMONES
ďź Estrogens cause increased liberation of insulin.
ďź Testosterone decrease blood sugar level.
113. Clinical aspects
ď Glycosuria: occurs when venous blood glucose concentration exceeds 9.5-
10.0mmol/L
ď Fructose-1,6-Biphosphatase deficiency causes lactic acidosis & hypoglycemia.
Diabetes Mellitus
A multi-organ catabolic response caused by insulininsufficiency
Muscle:
Protein catabolism for gluconeogenesis
Adipose tissue
Lipolysis for fatty acid release
Liver
Ketogenesis from fatty acid oxidation
Gluconeogenesis from amino acids and glycerol
Kidney
Ketonuria and cation excretion
Renal ammoniagenesis.
114. DENTAL ASPECTS OF
CARBOHYDRATES METABOLISM
Role of carbohydrates in dental caries
⢠Fermentable carbohydrates causes loss of caries
resistance.
⢠Caries process is an interplay between oral
bacteria, local carbohydrates & tooth surface
Bacteria + Sugars+ Teeth Organic acids
Caries
116. RECENT CLINICAL ISSUES RELATED TO
CARBOHYDRATES METABOLISM
Cystic Fibrosis
⢠CMD in Cystic Fibrosis is characterized by its high rates
and latent course.
⢠The patients with CMD have retarded physical⢠The patients with CMD have retarded physical
development, more pronounced morphofunctional
disorders in the bronchopulmonary system, lower lung
functional parameters, and more aggressive sputum
microbial composition. (SamoÄlenko VAet al.)
117. ⢠OGTT causes a 34% increase in the detection rate of
T2D in patients with gout.
⢠Carbohydrate metabolic disturbances are revealed in
CMD in Gout
the majority of patients with gout and associated
with obesity, hypertriglyceridemia, high serum UA
levels, chronic disease forms, the high incidence of
CHD and arterial hypertension.(Eliseev MS et al.)
119. ⢠Carbohydrate Calculator
⢠https://www.calculator.net/carbohydrate-calculator.html#
Or
⢠http://www.calculator.net/carbohydrate-
PER DAY INTAKE OF CARBOHYDRATE
⢠http://www.calculator.net/carbohydrate-
calculator.html?ctype=metric&cage=25&csex
=f&cheightfeet=5&cheightinch=10&cpound=
160&cheightmeter=163&ckg=74&cactivity=1.
375&x=85&y=10#