Biochemistry Revision E6.5

Biochemistry Revision 1 01 1
BIOCHEMISTRY REVISION 1 ----- Active space -----
Enzymes 00:00:14
Enzymes are specialized proteins → Act as biological catalyst.

Exceptions : Ribozymes (RNA that acts as catalyst) like SnRNA, Peptidyl
transferase, Ribonuclease P.
Types of enzymes :
Enzyme
Simple enzyme Complex enzyme

(Inactive) (Activator) (Whole enzyme/
Active)
Only protein part Protein part Non-protein part
(Apoenzyme)
Coenzyme : Cofactor : Prosthetic :

Low molecular wt Inorganic molecules. Covalently attached to
organic molecules. Eg : Metals. apoenzyme.
Eg : B complex vitamins.
Examples of cofactor Enzymes requiring specific cofactor
Zinc Carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase, ALP.
Magnesium Kinase, phosphatases, enolase.
Copper Tyrosinase (melanin synthesis), lysyl oxidase (covalent crosslinks of
collagen), xanthine oxidase (purine catabolism).
Molybdenum Xanthine oxidase, sulfite oxidase.
Iron Heme : Cytochromes, nitric oxide synthase, tryptophan pyrrolase.
Non heme : Succinate dehydrogenase, Aconitase.
Classification of enzymes : 7 classes.

Class no. Name of class Subclasses Remarks
I Oxido reductase Dehydrogenase NAD+ (vit B3)/ FAD (vit B2)/ NADP+ (vit B3)
are required.
Oxidase Eg : MAO, cytochrome C oxidase.
Oxygenase Eg : Hydroxylases (mono oxygenases)
Peroxidase H2O2 → H2O. Eg : Glutathione peroxidase
Catalase H2O2 → H2O. Present in peroxisome.
Reductase Requires NADPH.
Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

2 01 Biochemistry
----- Active space ----- Class Class Name Definition Examples

II Transferase Transfers functional Kinase, Any enzyme with ‘trans’.
group
III Hydrolase Breaks covalent bonds Digestive enzymes, Phosphatase, Arginase.
by adding H2O
IV Lyase Breaks covalent bond Any ‘Lyase’ named enzyme, Decarboxylase
without adding H2O (Simple decarboxylation requires PLP).
V Isomerase Produces isomers ‘Isomerase’ in its name, Racemace, Mutase.
VI Ligase Require ATP Synthetase, Carboxylase (requires biotin).
VII Translocase Ions channels/ pumps H+ pump, K+ channel.
Mechanism of enzyme action 00:15:05
Lowering of activation energy : (Activation energy = Difference between the

free energy of substrate & the transition state).
The standard free energy change : ΔG0
ΔG0 = ΔGP - ΔGS (Gibb’s free energy : G) E : Enzyme;
Enzymes lower the activation energy. S : Substrate;
Enzymes do not alter ΔG (free energy change). P : Product.
o
Mechanisms to lower activation energy :

• Covalent catalysis.
• Acid base catalysis.
• Catalysis by strain
• Catalysis by proximity
Theories behind the mechanism of action of enzymes :
Conformational
change
Emil Fischer’s template theory/ Lock and key model Daniel Koshland’s theory/Induced fit theory

Factors affecting enzyme activity 00:22:02

----- Active space -----
1. Substrate concentration :
Ist order Kinetics Zero order Kinetics
V ∝ [S]
Hyperbolic curve ↑ in substrate concentration → ↑ in rate
of reaction → Till it reaches Vmax .
Then no further ↑ in rate of reactions.
Km : Michaelis constant
Significance of Km :
• Denotes the affinity of enzymes towards the substrate.
• Higher the Km , lower is the affinity.
• Helps select the ideal substrate (with lower Km).
Vmax S Vi : Initial velocity;
Michaelis menten equation : vi = Vmax : Max. velocity.
Km + S
Line weaver burk plot/ Double reciprocal plot :

y = ax + b → Equation of line.
2. Enzyme concentration :
• Enzyme concentration is directly proportional Velocity (V)
to the velocity of reaction.
• V ∝ [E] → Straight line.
Enzyme conc. [E]
3. Temperature : Vmax
• Bell shaped curve.
Optimum temp.
• Optimum temperature in humans : 35°- 40°C.

• > 40°C : Sharp fall in rate of reaction
d/t denaturation of enzymes.
Vmax
4. pH of the medium :
• Bell shaped curve.
Optimum pH
• Optimum pH : 5 to 9 (normal).

4 01 Biochemistry

Enzyme inhibition 00:29:46
Competitive inhibition :
Here, the inhibitor is a structural
analogue of substrate and hence it
competes with the substrate for
binding to the active site.
Examples :
• Most of the drugs.
• Malonate (poison) : Inhibits
succinate dehydrogenase.
Vmax1 =
[S] [S]
Vmax remains constant. X-intercept moves towards zero.

Vmax1 = Vmax Y-intercept remain same.
KmI > Km Plot is shaped like ‘X’.
Non competitive inhibition : Without Inhibitor

The inhibitor is not a structural analogue
of substrate. It binds to a distinct site.
E+P at a very negligible rate. With Inhibitor
Eg : Most of the poisons. = Less products
[S]
[S]
V < Vmax
1
max
Vmax reduced → 1/Vmax (y intercept) increases.
Km remains constant. Km constant → (-1)/Km (x intercept) unchanged.
KmI = Km Plot is shaped like ‘v’.

Uncompetitive inhibition : ----- Active space -----

The inhibitor has no affinity towards free enzyme but it binds to the
enzyme-substrate (ES) complex.
[S] [S]
Vmax decreases. X-intercept moves away from zero.

Km1 decreases. Y-intercept increases.
Shape : Parallel.
Summary :
Uncompetitive Inhibition Noncompetitive Inhibition Competitive Inhibition

Parallel V shaped X shaped
Suicide inhibition/ mechanism based inactivation :
The unreactive inhibitor, using the mechanism of enzyme, becomes reactive
inhibitor & binds to the active site of enzyme irreversibly.
Examples :
• Allopurinol inhibits
Xanthine oxidase.
• Aspirin inhibits cyclooxygenase.
• Difluoro methyl ornithine inhibits ornithine decarboxylase.
Enzyme regulation 00:41:44
Enzyme regulation
Enzyme quantity Enzyme quality

At the level At the level
of gene of enzyme
Enzyme degradation Covalent Allosteric

Induction & Repression
modification regulation
Proteasomal Lysosomal
By Ubiquitin

6 01 Biochemistry

Allosteric regulation :
Allosteric enzymes : Their activity at substrate binding (active) site is modulated
by the presence of a modifier/effector.
+ve modifier : Activator (Allosteric activation).
-ve modifier: Inhibitor (Allosteric inhibition).
Properties of allosteric enzymes :

• Multi-subunit enzyme (quaternary structure).
• Usually are rate limiting enzymes.
• Substrate saturation curve : Sigmoid curve.
Follows a sigmoid kinetics d/t
cooperative binding. Binding of one substrate
favours binding of others to the same enzyme.
• Doesn’t follow Michaelis-Menten hyperbolic kinetics.
Binding constant (S0.5 or K0.5 )
Allosteric activation and inhibition :
Covalent modification/ hormonal regulation :

Well fed state ( Post prandial) Fasting state (Post absorptive)
High Insulin : Glucagon ratio. Low Insulin : Glucagon ratio.
Enzymes in dephosphorylated state. Enzymes are in phosphorylated state.
Glucagon → ↑ cAMP → Phosphorylation.
Enzymes in glycolysis, glycogen synthesis, Enzymes in glucuneogenesis, glycogenolysis,
fatty acid synthesis are active in fed state. lipolysis are active in fasting state.
Kinetic constants :
Vmax
Catalytic constant or Kcat =
Et
Et : Total enzyme concentration (E + Es).
Kcat
Catalytic efficiency of enzyme =
Km

Introduction to carbohydrates 00:00:10
Carbohydrate : Aldose or keto derivative of polyhydroxyalcohol.

Common monosaccharides : (Benedict’s test +ve).
No. of carbon atoms Aldoses Ketoses
Triose (simplest carbohydrates) Glyceraldehyde Dihydroxy acetone
Tetrose Erythrose Erythrulose
Pentose Ribose, Arabinose Ribulose,
Xylose (Epimer of Ribose) Xylulose (Epimer of Ribulose)
Hexose Glucose, Galactose, Mannose Fructose
Common disaccharides :
Reducing disaccharides : (Benedict’s test +ve). Non-reducing disaccharides :
Name Monomer units Linkage Name Monomer units Linkage
Maltose Glucose + Glucose α 1,4 Trehalose Glucose + Glucose α 1, 1
Isomaltose Glucose + Glucose α 1,6 Sucrose Glucose + Fructose α 1, β 2
Lactose Galactose + Glucose β 1, 4
Lactulose Galactose + Fructose α 1, β 4
Polysaccharides : 2 types.
• Homopolysaccharide. Eg : Glycogen, starch, cellulose.
• Heteropolysaccharide. Eg : GAG (mucopolysaccharides), pectin, agarose.
Dietary fibres (aka non starch polysaccharide) : Complex carbohydrate, not
digestible by humans, but fermented.
Note : Lignin is neither digested, nor fermented.
RDA is 40 g/2000 kcal.
• Soluble dietary fibre : In gums, mucilage, pectin.
• Insoluble (crude fibres) : In cellulose, hemicellulose, lignin.
Glycosaminoglycans (GAG) 00:11:23
Unbranched polysaccharide containing repeating disaccharide units of Amino +

Acid sugars.
General properties of GAGs:
• Negatively charged
• Cushioning effect.
8 02 Biochemistry

Special characteristics of GAG :
GAG Special characteristics
Keratan sulphate • No uronic acid.
• Maintains corneal transparency.
Hyaluronic acid • No sulphate group.
• Not covalently linked to proteins.
• Facilitates cell migration during morphogenesis & wound repair.
• Compressibility of cartilage in weight bearing.
Chondroitin sulphate • Compressibility of cartilage in weight bearing.
• Most abundant GAG.
Heparan sulphate Present in plasma membrane (act as receptors).
Heparin Anticoagulant
Dermatan sulphate Maintains the structure of sclera
Mucopolysaccharidoses (MPS) :
GAG is degraded in lysosomes.
GAG
Defect in GAG degradation → MPS (lysosomal storage disorder).
All mucopolysaccharidoses are AR except Hunter’s disease. Core Protein
Structure of GAG
Most common MPS : Sanfilippo > Hunter > Hurler.
Mucopolysacchridoses Enzyme defect
Hurlers Disease (MPS I H) α L – iduronidase
Scheie’ Disease (MPS I S) α L-iduronidase
Hunter’s Disease (MPS II) L-iduronate sulfatase
Sanfilippo disease (MPS III ) HS degradation
Morquio disease (MPS IV) Galactosamine 6 sulphatase
Maroteaux Lamy disease (MPS VI) N acetyl galactosamine sulfatase (Aryl sulfatase B)
I Cell Disease (resembles MPS as it N acetyl glucosamine (GlcNAc) phosphotransferase
affects GAG degradation)
Features MPS I-H MPS I-S MPS II MPS III MPS IV MPS VI
Mental deficiency + Absent + + Absent Absent
Corneal clouding + + Absent Absent + +
Visceromegaly + + + Absent Absent +
Leucocyte (Reilly body) inclusions + + + + Absent +
All MPS have coarse facial features, short stature, and dysostosis multiplex.
Coarse facies Claw hand Corneal clouding Reily body inclusions Bullet shaped
in leucocytes middle phalanx

Glucose transporters 00:28:31 ----- Active space -----
Classified as : Sodium dependent (SGLT) & sodium independent (Glut)

Glucose Location Points to remember
transporter
SGLT 1 Intestine (Apical/ luminal side), Proximal Absorption of glucose. Unidirectional.
tubules Na+ glucose symport.
SGLT 2 Proximal tubules 2° active transport.
Glut 1 Brain, kidney, placenta, colon, Widely located.
retina, RBC High affinity for glucose (low km).
Glut 2 Sinusoidal cells (liver), β cells (pancreas), Absorption of glucose.
Intestine (serosal side), kidney Low affinity (high km).
Glut 3 Neurons, placenta, kidney Very high affinity.
Glut 4 Heart, skeletal muscle, adipose tissue Insulin dependent Glut.
Glut 5 Testes, intestine Absorption of fructose.
Glut 6 Spleen, leukocytes No transporter function (pseudogene).
Glut 7 Liver, smooth ER Absorption of glucose.
Glut 8 Blastocyst
Glut 9 Intestine, kidney Urate transporter, Mutation : 1˚Gout.
Applied aspects :
• Mutated SGLT2 → Lowers renal threshold → Renal glycosuria (Blood glucose normal,
Urine Benedict’s test +ve).
• SGLT2 inhibitors (gliflozins) : Oral hypoglycemic agents, S/E : UTI.
• ORS : Glucose + sodium (SGLT 1 in intestine).
Body in well fed state :
High insulin : glucagon ratio Glut 2 in liver (high Km)
Glucose → Glucose 6 phosphate

Increased Glut 4 in heart,
1. Glycolysis → TCA cycle.
muscle (↑glycolysis, ↑glycogen synthesis),
2. Excess glucose : Glycogen synthesis.
adipose tissue (↑fatty acid synthesis).
3. HMP shunt : NADPH produced (used for
fatty acid synthesis).
Body in fasting state :
↓
Low insulin : glucagon ratio → Enzymes in phosphorylated state →
Pathways activated : Glycogenolysis (in liver), gluconeogenesis
Glycolysis/ EMP pathway 00:43:53
In all organs (site : cytoplasm). Both aerobic & anaerobically.

10 02 Biochemistry

Preparatory phase :
(Irreversible)
Hexokinase/glucokinase
Glucose Glucose 6 phosphate
1 ATP 1 ADP
(reversible) Phospho hexose isomerase
Fructose 6 phosphate
1 ATP Phospho fructokinase 1
ATP used = 2 1 ADP
Fructose 1,6 bisphosphate
Aldolase (reversible)
Dihydroxy acetonephosphate (DHAP) Glyceraldehyde 3 phosphate (G3P)
Phosphotriose isomerase
Pay off phase :

Glyceraldehyde3 phosphate
Gly 3 Po4 dehydrogenase Pi

ETC
NAD + 1 NADH = 2.5 ATP x 2
Reversible step
Inorganic PO4 added NADH & H+ = 5 ATP
1,3 Bisphosphoglycerate (1,3 BPG)

1,3 BPG Kinase ADP
(Substrate level phosphorylation)
(only reversible kinase) ATP x 2 = 2ATP
3 phosphoglycerate
3 phosphoglycerate mutase
2 phosphoglycerate
Enolase
Mg2+/Mn2+ H20
Phosphoenol pyruvate (PEP)
Pyruvate kinase ADP (Substrate level phosphorylation)
(Irreversible step; Regulatory step) ATP x 2 = 2ATP
Pyruvate
Anaerobic glycolysis :
Occurs in the RBCs where there are no mitochondria or lack of oxygen.
No net generation of NADH. Glucose
Lactate
2 Gly 3 Po4 NAD+ Lactate
NADH dehydrogenase
1,3 BPG Pyruvate

Important enzymes : ----- Active space -----

• Enzyme induced by insulin : Glucokinase.
• Enzyme that regulate glucose level following a meal : Glucokinase.
• Rate limiting step/Commited step of Glycolysis is PFK-1.
• Inorganic Phosphate is added in G3P Dehydrogenase.
• Irreversible steps of Glycolysis : All Kinases except 1,3 B P Glycerate Kinase.
• Substrate level Phosphorylation : 1,3 BP Glycerate Kinase & Pyruvate Kinase.
Energetics :
Pathway ATPs generated ATPs consumed Net ATPs
Anaerobic Glycolysis 4 2 2
Aerobic Glycolysis 9 2 7
1 mol of glucose in aerobic condition (aerobic glycolysis = 7 ATP, 32
2 x Pyruvate →Acetyl CoA = 2 x NADH = 2 X 2.5 ATP = 5 ATP
2 x TCA cycle = 2 x 10 ATP = 20 ATP)
Pyruvate dehydrogenase 00:54:13
Site : Mitochondria.
Multienzyme complex :
3 enzymes 5 coenzymes
E1 : Pyruvate dehydrogenase Thiamine Pyrophosphate (vit B1).
E2 : Dihydrolipoyl transacetylase Lipomide.
E3 : Dihydrolipomide dehydrogenase FAD (vit B2), NAD (vit B3), CoA (vit B5).
Net reaction (oxidative decarboxylation) :
Significance of pyruvate dehydrogenase :

Link reaction
(Links glycolysis and TCA) Enters TCA
Excess PDH
Carbohydrates Glucose Pyruvate Acetyl CoA Fatty acids
Irreversible
+ Glycerol
No enzyme
TAG (Fats)
Fat (Triacylglycerol) can’t be converted to Glucose except Glycerol & PropionylCoA.
Clinical significance : (Leigh syndrome)

Metabolic defect (PDH Complex : E1 MC affected) → No production of Acetyl CoA
→ Increased pyruvate → Converts to lactate → Lactic acidosis.
12 03 Biochemistry
----- Active space ----- BIOCHEMISTRY REVISION 3
Glycogen metabolism 00:00:20
Glycogen present in :
• Liver (source of blood glucose during fasting).
• Skeletal muscle cells (energy during exercise).
Glycogen linkage :
• Linear side (α 1, 4 glycosidic linkage).
• Branching point (α 1, 6 linkage).
Glycogen synthesis :
1. Synthesis of UDP glucose.
2. Action of glycogen synthase →
Glycogenolysis :
In early fasting state (4-16 hours without food).
1. Action of Glycogen phosphorylase :
• Rate limiting enzyme.
• Coenzyme : PLP (Vitamin B6).
• Creates polymers of glucose with
short branches (Limit dextrin)
2. Debranching enzyme
(Bifunctional with tandem action).
3. Conversion of glucose-1-PO4 to glucose

• Liver : Mediated by G-6-phosphatase (in SER).
• Muscle : PGM
G-1-p G-6-P Pyruvate Lactate
Anaerobic glycolysis 3 ATP

(no hexokinase step)
Factor favouring glycogen synthesis Factors favouring glycogenolysis

Insulin Glucagon & epinephrine

Glycogen Storage Disorders (GSD) 00:13:43 ----- Active space -----
Types Enzyme defect Clinical features

• Doll like facies, thin extremeties.
Type 1/ • Massive hepatomegaly.
Glucose 6
Von Gierke’s Biochemical hallmarks :
Phosphatase.
(Liver GSD). • Hypoglycemia, HyperuricemiaHyperlipidemia
• Lactic acidosis, Ketosis.
Type 11 / Pompes Acid α 1-6 • HCM & cardiomegaly.
(Muscle GSD) : glucosidase/ Acid • Floppy infant (extreme hypotonia).
lysosomal defect. maltase. • Child die by 2 years (cardiac failure).
Type 111 / Cori’s/ • No lactic acidosis, No hyperuricemia.
Limit dextrinosis. Debranching enzyme. • Liver cirrhosis +.
(Liver GSD) : • Liver enzymes (AST & ALT).
• Abnormal glycogen.
Type IV/Anderson • No lactic acidosis, No hyperuricemia.
Branching enzyme.
/Amylo-pectinosis. • Liver failure (fatal) : Dies by 5 years
• Liver enzymes (AST & ALT).
• Exercise intolerance
Type V /McArdle’s Muscle glycogen
• 2nd wind phenomenon seen.
(Muscle GSD) phosphorylase.
• S.lactate after exercise.
Type VI / Her’s Hepatic glycogen • No severe hypoglycemia.
(liver GSD) phosphorylase.
• Exercise intolerance, Hemolysis.
Type VII / Tarui’s Muscle & erythrocyte
• No 2nd wind phenomenon.
(Muscle GSD) phospho-fructokinase.
• S.lactate after exercise
Fanconi Bickel GLUT 2
syndrome (low affinity)
Type 0 Glycogen synthase • No glycogen deposition ; No Hepatomegaly
Liver GSD : Type I, III, VI, O.

Muscle GSD : Type V, VII, O, II.
Von Gierke’s Pompe’s
Regulation of glycogen metabolism 00:19:07
Types :
1. Covalent modification.
• In fed state : Insulin activates phosphatase → activates glycogen synthase
& inactivates glycogen phosphorylase.
14 03 Biochemistry

• In fasting state : Glucagon activates cAMP dependent protein kinase which in
turn activates Glycogen phosphorylase.
Note : Calcium from SER of contracting muscle activates glycogen phosphorylase
via Ca-calmodulin complex & causes glycogenolysis.
2. Allosteric modification :
One liners :
• Liver glycogen is depleted after 12- 18 hours of fasting.
• Common enzyme for glycogenolysis & glycogen synthesis : Phosphoglucomutase.
• First product of Glycogenolysis : Glucose 1 phosphate.
• Glycogenolysis enzyme absent in the muscle : Glucose 6 phosphatase.
• Rate limiting enzyme of glycogen synthesis : Glycogen synthase.
• Glycogen synthase is active in dephosphorylated state.
• Glycogen phosphorylase is active in phosphorylated state.
• Glucagon & Epinephrine acts via cAMP dependent protein kinase A.
• c AMP independent Ca- Calmodulin dependent activation of glycogenolysis is present.
• 5’AMP is an allosteric activator of muscle phosphorylase.
HMP pathway 00:39:18
aka pentose phosphate pathway/Dicken Horecker pathway.

Organelle : Cytoplasm.
No ATP generation.
Rate limiting step : Glucose 6 phosphate dehydrogenase.
HMP phase 1 (oxidative phase) HMP phase 2 (non oxidative phase)
Irreversible Reversible
Generate NADPH Generate pentoses → DNA synthesis
G6PD (rate limiting enzyme) Produces glyceraldehyde-3-PO4→ Glycolysis→ Acetyl CoA
Function of NADPH :
1. Reductive biosynthesis of fatty acids & cholesterol :
• Occurs in liver, adipose tissue, adrenal cortex, gonads.
2. Free radical scavenging (H2O2 → H2O) : ----- Active space -----

• Occurs in RBC (membrane integrity) & lens (transparency).
3. Respiratory burst : Phagocytosis by WBC.
• NADPH oxidase require NADPH.
• Disorder associated : Chronic granulomatous disease.
4. Nitric oxide synthase : Require NADPH.
5. Cyt P450 (Phase 1 detoxification reaction) : Require NADPH.
Other sources of NADPH :
• Isocitrate dehydrogenase (cytoplasmic).
• Malic enzyme( NADP Malate Dehydrogenase).
G6PD deficiency (XLR) :
• M/c enzyme deficiency in human beings (2nd m/c : Pyruvate kinase).
• Deficiency of NADPH.
• Precipitated by sulfa drugs, fava beans.
• Clinical features :
1. Hemolysis (jaundice + anemia).
2. Methemoglobinemia.
Erythrocyte transketolase is an indicator of thiamine status.
Gluconeogenesis 00:48:16
In late fasting state (16-48 hours without food).

Organelle : Cytoplasm + mitochondria.
Non-carbohydrate substrates converted to glucose :
• Lactate : Glucose lactate cycle (corI’s cycle).
• Glucogenic amino acids (Alanine) : Glucose alanine cycle (Cahill cycle).
• Glycerol.
• Propionyl CoA.
Acetyl CoA is never a substrate. It is allosteric activator of pyruvate carboxylase.
Key enzymes :
Gluconeogenesis Glycolysis (irreversible steps)
Pyruvate carboxylase. Pyruvate kinase
PEP carboxykinase.
Fructose 1,6 Bisphosphatase Phosphofructokinase
Glucose 6 phosphatase Hexokinase
Malate aspartate shuttle :

• Transport of oxaloacetate from mitochondria to cytoplasm.

16 03 Biochemistry

Reciprocal regulation of glycolysis & gluconeogenesis :
Enzymes Activator
Inhibitor
Phospho • 5’ AMP. • Citrate.
Fructokinase-1 • Fructose 6 Phosphate. • ATP.
• Fructose 2,6 Bisphosphate. • Low pH.
Pyruvate Kinase Fructose 1,6 Bisphosphate.
Pyruvate • CoA , NAD+ , ADP • ATP.
Dehydrogenase • Pyruvate. • Acetyl CoA.
• NADH.
Pyruvate Carboxylase Acetyl CoA. ADP.
Uronic acid pathway/synthesis of ascorbic acid : Humans cannot synthesis

vitamin C (d/t absence of L Gulanolactone oxidase).
Polyol/sorbitol pathway : Responsible for development of cataract in DM.
Galactose metabolism 01:01:01
Metabolised exclusively in liver.

Galactose tolerance test : Liver
function test.
Types of galactosemia :
1. Classic galactosemia :
Galactose 1 PO4 uridyl transferase defect.
2. Non classic galactosemia :
a. Galactokinase defect : Oil drop cataract.
b. UDP hexose epimerase defect.
Fructose metabolism 01:07:18
Fructokinase
Fructose Fructose 1 Phosphate
Aldolase B
Glyceraldehyde Dihydro acetone phosphate
Glyceraldehyde 3 Phosphate
Enter glycolysis
Note : Phosphofructokinase (rate limiting step of glycolysis) is not involved in

fructose metabolism.

Metabolic disorder Enzyme Defect Features ----- Active space -----
Hereditary Fructose Aldolase B Resembles

Intolerance (HFI) galactosemia.
Essential Fructosuria Fructokinase Benign condition
Essential pentosuria Xylulose reductase/Xylitol Benign condition.
dehydrogenase Bial’s test +ve.
Galactosemia HFI
Age of onset First 2 weeks. ~ 6 months.
Trigger Breast milk Weaning food
• Jaundice, seizures, lethargy. Resemble
Clinical • Failure to thrive , Hypoglycemia. galactosemia.
features • Oil drop cataract (Galactitol). But no cataract.
• Prone for E coli sepsis.
Accumulating Galactose 1 Phosphate. Fructose 1 Phosphate
substance (toxic to liver).
Specific test (galactose, fructose) :
• Benedict test +ve for reducing sugars.
Investigations
• Glucose oxidase test -ve for glucose.
Direct enzyme assay.
Treatment Non lactose diet. Withdraw breast milk. Fructose free diet.
TCA cycle 01:12:23

18 03 Biochemistry

Inhibitors of TCA cycle :
1. Flouroacetate inhibits aconitase.
2. Arsenate inhibits alpha keto glutarate dehydrogenase.
3. Malonate inhibits succinate dehydrogenase.
• Truly an amphibolic pathway.

• Final common oxidative pathway of lipids, carbohydrates & Proteins.
• Acetyl CoA is completely oxidised.
• Unidirectional steps : Citrate synthase & α keto glutarate dehydrogenase.
• 3 NADH and 1 FADH2 are produced.
• Total No of ATPs generated by one turn of TCA cycle : 10 ATPs.
• Succinate dehydrogenase is linked to complex II of ETC.
• FADH2 is produced by Succinate dehydrogenase.
• Major anaplerotic (filling up) reaction in TCA : Pyruvate carboxylase.
Vitamins in TCA cycle :

1. Pantothenic acid : In CoA.
2. Thiamine : In α KGOH.
3. Riboflavin : In FAD.
4. Niacin : In NAD.
Oxidative phosphorylation 01:19:10
• Oxidation coupled with phosphorylation by means of H+ gradient.

• Every reducing equivalent entering ETC is converted to ATP.

Complexes of ETC Inhibitors ----- Active space -----
• NADH Q oxidoreductase. Rotenone,

Complex 1 • PUmps 4 H+ into intermembrane space. Amobarbital,
Piercididin A.
Complex • Succinate Q oxidoreductase. Malonate,
II • Does not pump H . +
Carboxin, TTFA.
Complex • Q cyt c oxidoreductase/Cyt b -cyt C1 complex. Antimycin A,
III • PUmps 4 H+ into intermembrane space. BAL (Dimercaprol)
• Cyt C oxidase. CO, Cyanide, H2S,
Complex
• Final electron acceptor. Sodium azide.
IV
• PUmps 2 H+ into intermembrane space.
• Point of phosphorylation. Atractyloside,
Complex
• Has 2 subunits : Oligomycin,
V (ATP
1. F0 : Proton channel. Venturicidin.
synthase
2. F1 : Various subcomplex (Gamma : Rotatory
complex)
channel, Beta : Convert ADP to ATP).
Uncouplers of oxidative phosphorylation :

Uncouplers of oxidative phosphorylation
Chemical • 2,4 Dinitrophenol ; Dinitrocresol ; Aspirin in high dose.
uncouplers • FCCP (Fluoro Carbonyl Cyanide Phenyl hydrazine).
Physiological • Thermogenin (uncoupling Protein I) , Thyroxine.
uncouplers • Long chain fatty acid.
Ionophores • Valinomycin & Gramicidin.
High energy compounds :
Compounds which yield energy on hydrolysis (atleast 7 KCal/mol).
Examples : ATP, 1,3 Bisphosphoglycerate, Acetyl CoA, succinyl CoA,
Phosphoenolpyruvate, Phospho creatine, Phospho arginine.
Respiratory quotient (RQ) :
Ratio of CO2 produced/O2 consumed.
Substrate RQ Substrate RQ
Carbohydrates 1.00 Mixed diet 0.80-0.85
Protein 0.81 Exclusive carbohydrate diet 1.00
Fat 0.71 Excess carbohydrate diet ≤ 1.00
Alcohol 0.66
20 04 Biochemistry
Lipids 00:00:17
These are heterogenous group of compounds insoluble in polar solvents but

soluble in nonpolar solvents like chloroform or ether.
Essential Semi-essential Omega 3 fatty acids Omega 6 fatty
fatty acids fatty acids acids
Linoleic acid Arachdonic acid. A : Alpha linolenic acid. G : GLA
T : Timnodenic acid. L : Linoleic acid.
Alpha- Gamma Linolenic C : Cervonic acid aka A : Arachidonic acid.
linolenic acid acid (GLA). Docosahexaenoic acid
(DHA).
Docosa hexaenoic acid or cervonic acid :

Low DHA associated with retinitis pigmentosa.
Function : Development of foetal brain and retina.
Trans fatty acid :

• Partially hydrogenated edible oil (margarine or cake butter).
• Most Unsaturated fatty acids exist in cis form, on heating Trans form.
• Present in bakery items, fried foods and processed food .
• Deleterious effect are :
a. TAG , LDL, HDL.
b. Cardiovascular risk.
c. Inflammation.
d. Insulin resistance.
Omega 3 fatty acids :

• Cardiovascular risk.
• Replaces arachidonic acid (source of inflammatory markers) in platelets.
• Thromboxanes and tendency of platelet aggregation.
• inflammation.

Richest sources of fatty acids : ----- Active space -----
Fatty acid Richest source

SFA (Saturated Fatty Acid) Coconut oil
PUFA (Poly UFA) Safflower > Sunflower. Least : Coconut oil.
Linoleic acid Safflower oil.
Alpha linolenic acid Flax seed oil
MUFA Mustard/Rape seed oil.
Trans fat Vanaspati/Dalda
Phospholipids 00:09:05
Two types : 1. Glycerophospholipids 2. Sphingophospholipid

1. Glycerophospholipids :
Glycerol + 2 Fatty acids(FA) + Phosphate + Nitrogenous base.
Diacyl glycerol(DAG)
Glycerophospholipid Constituents Uses

Phosphatidic Acid (PA) DAG + • Cell membrane
Phosphate
Lecithin/phosphatidyl PA + Choline • Most abundant phospholipid in cell mem-
choline brane.
• Lung surfactant.
• Store house of choline.
Cephalin PA + Ethanol- • Cell membrane.
amine
Cardiolipin PA + Glycerol • Only antigenic phospholipid.
(diphosphatidyl + PA • Present in inner mitochondrial membrane.
Glycerol) • False +ve result in test for syphilis (VDRL).
• Associated with Barth syndrome/Cardi-
oskeletal myopathy (mitochondrial disorder).
Phosphatidyl serine PA + serine Apoptosis.
Phosphatidyl inositol PA + Inositol Second messenger.
2. Sphingophospholipid :
Sphingosine + FA + Phosphate+ Nitrogenous base.
Ceramide

22 04 Biochemistry
----- Active space ----- Sphingophospholipid Constituents Uses

Sphingomyelin Ceramide + PO43- + Choline. • Myelin sheath
• White matter of brain.
Note : L/S Ratio (Lecithin/Sphingosine) : Indicator of lung maturity.

In mature lung : More lecithin present.
Glycolipids 00:15:15
Not a phospholipid.
Ceramide + Carbohydrate.
Glycosphingolipid Constituents Uses
Cerebroside Ceramide a. Glucocerebroside : Extraneural tissue.
+ b. Galactocerebroside : Neural tissue.
Monosaccharide
Globoside Ceramide + Oligosaccharide
Ganglioside Ceramide + Oligosaccharide + N-acetyl Neuraminic acid.
(GM1, GM2, GM3)
Sphingolipidoses : Defect in sphingolipids degradation (takes place in lysosomes).
Disease Enzyme defect
GM 1 Gangliosidoses ß Galactosidase.
Tay Sach’s disease ß Hexosaminidase A.
(GM 2 Gangliosidoses)
Sandhoff’s disease ß Hexosaminidase A & B.
(GM 2 Gangliosidoses)
Krabbe’s disease ß Galactocerebrosidase/ ß Galactosidase
Niemann Pick Type 1 Sphingomyelinase
Gaucher’s disease ß Glucocerebrosidase/ß Glucosidase
Metachromatic Aryl Sulfatase A
leukodystrophy
Farber’s disease Ceramidase
Wolman’s Disease(LSD) (not an SPL) Acid Lipase
Fabry’s disease α-Galactosidase
In the table above, LSD-Lysosomal storage disorder, SPL-Sphingolipidoses.
Gaucher’s Disease : M/C lysosomal storage disorder.
No mental retardation (MR), no cherry red spot.
Bleeding tendency, pain and pathological # of long bones.
Crumpled tissue paper Visceromegaly Erelenmeyer flask

appearance on bone marrow deformity
Fabry’s disease : XLR, No MR, hypohydrosis, Fabry’s crisis (pain in proximal joints).
Angiokeratoma Maltese cross Whorled appearance in lens; Lenticular

(urine microscopy) opacity
Krabbe’s disease : Severe neurological deficit. No visceromegaly.
Multinucleated globoid cell inclusion bodies in

white matter of brain. Opisthotonus posture
Wolman’s disease/cholesterol ester storage disorder :
• Not a sphingolipidoses, type of LSD.
• Deficiency : Acid lipase.
• C/F : Watery green diarrhoea.
• Pathognomic feature : Calcification of adrenals.
Important points for sphingolipidoses :
• All are autosomal recessive except Fabry’s disease (X linked recessive).
• No cherry red spot on the macula : Fabry’s disease, Gaucher’s disease.
• No mental retardation : Fabry’s disease, Gaucher’s type I.
• Angiokeratoma : Fabry’s disease, GM 1 gangliosidoses.
• Resembles rheumatoid arthritis : Farber’s disease.
• No visceromegaly : Metachromatic leukodystrophy, GM 2 gangliosidoses,
Krabbe’s disease.
• Zebra body inclusion : Niemann Pick’s disease.

24 04 Biochemistry

Metabolism of lipids 00:27:22
Well fed state Fasting state

High insulin/glucagon ratio. Low insulin/glucagon ratio.
Lipogenesis Lipolysis
Glycogenesis Gluconeogenesis
TAG synthesis, cholesterol synthesis. Ketone bodies synthesis, fatty acid oxidation.
Lipolysis :
Acyl CoA Acyl CoA Acyl CoA
TAG HSL DAG HSL 2,MAG MAG esterase Glycerol
Hormone Sensitive Lipase (HSL)

Stimulated by Glucagon, glucocorticoids, epinephrine, TSH,
thyroxine, ACTH, MSH
Inhibited by Insulin, nicotinic acid, PGE 1
Fatty acid oxidation :

Stages of fasting Source of glucose
Early fasting Glycogenolysis
(4-16 hrs)
Fasting Gluconeogenesis
(16-48 hrs)
Prolonged fasting (starvation) Lipolysis
(2-5 days)
Prolonged starvation Muscle proteolysis
(> 5 days)
Note :
Glycerol released during lipolysis is a substrate for gluconeogenesis.
FA oxidation is a source of ATP for gluconeogenesis.
FA oxidation ketone body synthesis.
Beta-oxidation of fatty acids :

• Site : Liver, adipose tissue, skeletal muscle.
• Organelle : Mitochondria.
• Steps of FA oxidation :
(1). Preparatory. (2) Beta-oxidation.
Preparatory : ----- Active space -----

a. Activation of FA : Occurs in cytoplasm.
Acyl CoA Synthetase/Thiokinase
FA Acyl CoA
1 ATP 1 AMP
Uses : 2-PO43-
b. FA transport :
• Cytoplasm → Mitochondria.
• Gateway of oxidation : CPT-1
(rate limiting enzyme).
• Malonyl CoA inhibits CPT-1.
Note : FA < 14 C do not require Carnitine.
Beta-oxidation : Energetics of beta oxidation :

Acyl CoA No. Of acetyl CoA = No of C atoms
FAD 2
FADH2 Acyl CoA Dehydrogenase 1 acetyl CoA = 10 ATP.
α β Unsaturated Acyl CoA If number of Acetyl CoA = n
Then no. of cycles of β-oxidation = n - 1
Hydratase + H20
1 cycle of β oxidation : (1 NADH + 1 FADH2) ATPs
Hydroxy Acyl CoA (2.5 + 1.5) = 4 ATPs
NAD+
Hydroxy Acyl CoA DH For palmitic acid (C16) :
NADH+ H+
KetoAcyl CoA No of acetyl CoA = 16/2 = 8 → 80 ATP.
No of cycles = 8-1 = 7 → 7 x 4 = 28 ATP.
Acyl CoA Acetyl CoA Total ATP generated = 80 + 28 = 108 ATP.
2 ATP consumed by thiokinase → 106 ATP
Disorders of fatty acid oxidation : (net ATP produced).
1. Jamaican vomiting sickness :
D/t consumption of unripe Ackee fruit.
C/F : Sudden onset of vomiting, fatal condition.
Toxin : Hypoglycin (inhibits acyl CoA dehydrogenase)
ß oxidation, Gluconeogensis & Ketone body synthesis.
2. MCAD deficiency (Medium Chain Acyl CoA Dehydrogenase deficiency) :

• Medium chain fatty acid oxidation is affected.
• Leads to SIDS (Sudden Infant Death Syndrome). Fatal condition.
• /no ß oxidation alternate pathway Omega (w) oxidation dicarboxylic acid.
• Diagnosis : Hypoglycemia, No ketone bodies.
• Treatment : Frequent meals with low fat and high carbohydrates.
26 04 Biochemistry
----- Active space ----- Summary of oxidation of fatty acids :
Fatty acid oxidation Site Important points

Beta oxidation :
Saturated fatty acid Mitochondria
Unsaturated fatty acid Mitochondria Acyl CoA DH step is
bypassed.
1.5 ATPS less for each
double bond.
Odd chain fatty acid Mitochondria (Acetyl CoA) X n + Propionyl
CoA (glucogenic)
Alpha oxidation Peroxisome & No ATPs
(minor oxidation) Endoplasmic reticulum
Omega oxidation Micrososmes (SER) No ATP
Dicarboxylic acid produced.
Zellweger syndrome/cerebrohepatorenal syndrome :

CF : Frontal bossing, epicanthal folds, hypertelorism, mongoloid facies.
Ophthalmic examination : Bruschfield spots in the iris.
Defect : Mutation in PTS (Peroxisomal Targeting Sequence) → Defect in
oxidation of VLCFA & alpha oxidation.
Blood picture : S.VLCFA (very long chain FA).
S. Phytanic acid.
Peroxisomes are /absent.
Refsum’s disease :
Defect : Phytanoyl CoA hydroxylase/oxidase enzyme (alpha oxidation).
C/F :
• Pigmentary retinopathy.
• Peripheral neuropathy.
• Icthyosis.
• Cardiac arrhythmia.
Diagnosis : S. Phytanic Acid.
Treatment : Avoid phytanic acid (green leafy vegetables, dairy products).

Ketone body synthesis : ----- Active space -----

Site : Exclusively in liver mitochondria.
Note : Ketone body is not utilised in liver (thiophorase absent) and RBC
(mitochondria absent).
Acyl CoA
β oxidation β-OH Butyrate
(Acetyl CoA) X N
Acetoacetyl CoA
Mitochondrial HMG CoA Acetoacetate
Synthase -RLE (rate limiting) Thiophorase
HMG CoA
HMG CoA Lyase Acetoacetyl CoA
Acetoacetate
(1˚ Ketone body) Acetyl CoA
Acetyl CoA
Dehydrogenase
CO2
Acetone β-OH Butyrate
RLE : Rate Limiting Enzyme.
• Acetoacetate & β-OH-butyrate are used in extrahepatic tissue.

• Acetone is excreted by lungs.
Fatty acid synthesis :

• Organelle : Extramitochondrial (cytosol).
• Starting material : Acetyl CoA.
• Transporter of acetyl CoA : Citrate (tricarboxylic acid transporter).
• Enzyme that releases acetyl CoA : ATP citrate lyase.
Acetyl CoA Carboxylase (RLE)

Acetyl CoA(2C) Malonyl CoA(3C)
ATP ADP
Biotin
CO2
Fatty acid synthase complex :
1. Condensing unit : Has 2 enzymes.
2. Reducing unit : Has 3 enzymes, NADPH required.
3. Releasing unit (thioesterase).
4. Acyl carrier protein (has vitamin B5).
28 04 Biochemistry

Cholesterol synthesis :
• Exclusive animal sterol.
• Not a metabolic fuel.
• Organ : Liver, adrenal cortex, adipose tissue, gonads.
• Organelle : Cytoplasm, SER.
• Substrate : Acetyl CoA.
Note : Statins inhibit HMG CoA reductase competetively.
• Vitamin D.
Acetyl CoA Cholesterol • Steroid hormone.
+Acetyl CoA • Bile acid.
Acetoacetyl CoA
Cytoplasmic HMG CoA
+Acetyl CoA
Synthase.
HMG CoA
HMG CoA RLE
Reductase.
Mevalonate Isoprenoid Unit (5C)
Bile acid synthesis :

Site : Liver & intestine.
Cholesterol
7 α Hydroxylase(RLE)
Liver 7 OH Cholesterol
Cholic Acid Chenodeoxycholic Acid

1˚Bile acids:
Intestine Enterohepatic
2˚Bile acids: Deoxycholic Acid Lithocolic Acid Circulation
Lipoproteins : 01:08:33
Electrophoretic pattern of plasma

Chylomicrons VLDL LDL HDL ----- Active space -----

Source Intestine Liver VLDL (LP cascade Liver & intestine
pathway)
Composition Max TAG High TAG Maximum Cholesterol Lowest TAG.
Lowest cholesterol Low cholesterol Low TAG High cholesterol.
Functions Carries exogenous Carries Delivers cholesterol Delivers cholesterol from
(dietary) TAG to endogenous TAG to peripheral tissues peripheral tissues to
peripheral tissues. to peripheral and back to liver. liver for elimination.
tissues.
Apolipoproteins Apo B48 : Apo B100, Apo B100 Apo AI, Apo C,
(Unique to chylomicron) Apo CII, Apo D,
Apo CII, Apo E Apo E Apo E
Characteristics Minimum density. Maximum density
Maximum size. Minimum size.
Remains at Origin Fastest electrophoretic
mobility
Hyperlipoproteinemias :
Disease Molecular De- Serum levels
fect
Type 1 Familial Chylomicronemia Syndrome : Lipoprotein CM > VLDL
Lipase TAG
Apo C11. Cholesterol = Normal
Type I1A Familial Hypercholesterolemia/ LDL receptor LDL ; Cholesterol
FDB(Familial Defective apo B) ApoB-100 TAG normal
Sitosterolemia ABCG5 & ABCG8 Secretes out plant sterol
(Also a type of type 11 hyperlipoproteinemia) (not normal in animals)
LDL
Type 111 Apo E TAG
Familial combined hyperlipoproteinemia Cholesterol
(Broad ß disease/ Remnant removal disease)
Hypolipoproteinemias :
Disease Molecular Defect Serum levels

Abetalipoproteinemia Microsomal Triglycerides Nascent CM
transfer proteins Nascent VLDL,IDL,LDL
Tangier’s disease Mutation ABCA-1
Fish eye disease Partial LCAT deficiency
Norum’s disease Complete LCAT deficiency

30 04 Biochemistry

Type 1 hyperlipoproteniemias :
Familial chylomicronemia syndrome.
Eruptive xanthoma Lipemia retinalis Milky white plasma/

strawberry coloured
Type 11 hyperlipoproteniemias :
Familial hypercholesterolemia.
Corneal arcus
Xanthomas
Achilles tendon
Type 111 hyperlipoproteinemias : Xanthoma
Familial dysbetalipoproteinemia
Tubero eruptive xanthoma Palmar xanthoma

(bunch of grapes) (yellowish discoloration of palmar creases).
Tangier’s disease :
Yellowish/orange tonsil
Amino Acid (AA) chemistry : amino H

acid
NH2- C -COOH
α
Most AA are α-AA. R variable side chain
Classification of amino acids 00:00:43
I. Based on side chain :

Sl No. Side chain AA
1. Aliphatic Simple Glycine, Alanine
Branched Leucine, Isoleucine, Valine
2. OH group Serine, Threonine, Tyrosine
3. Sulphur group Cysteine, Methionine
4. Acid group (-COOH) Aspartic acid, Glutamic acid
5. Amide group (-CO-NH2) Asparagine
Glutamine
6. Basic (-NH2) Histidine (aromatic), Arginine, Lysine
7. Aromatic Benzene ring Phenylalanine
Phenol ring Tyrosine
Indole ring Tryptophan
8. Imino acid (pyrrolidine ring) Proline
II. Based on side chain characteristics :

Polar Non polar
Charged Uncharged 1. Branched chain AA.
1. Acidic AA : 1. Amides : 2. Aromatic AA :
• Aspartic acid. Asparagine, Glutamine. • Tyrosine & Tryptophan.
• Glutamic acid. 2. OH group : • Phenylalanine.
2. Basic AA : Serine, Threonine. 3. Simple AA : Alanine.
• Histidine. 3. Simple AA : Glycine. 4. Sulphur group :
• Arginine. 4. Sulphur group : Cysteine. Methionine.
• Lysine.

32 05 Biochemistry

III. Based on metabolic fate :
Purely ketogenic Both glucogenic and ketogenic
• Leucine, Lysine. • Phenylalanine, Isoleucine, Tyrosine, Tryptophan.
IV. Based on nutritional requirement (Essential amino acids)

• Methionine. • Valine. • Phenylalanine.
• Threonine. • Isoleucine. • Lysine.
• Tryptophan. • Leucine • Histidine.
Note : All other AAs are non-essential. • Arginine (semi-essential).
Other amino acids :
Selenocysteine :
• 21st protein forming amino acid.
Enzymes containing
• Stop codon : UGA.
selenocysteine :
• Precursor AA : Serine.
i. Glutathione peroxidase.
• Formed by cotranslational modification.
ii. Thioredoxin reductase.
Pyrolysine :
iii. Deiodinase.
• 22nd protein forming AA.
iv. Selenoprotein p.
• Stop codon : UAG (recoding).
• Formed by cotranslational modification of precursor AA : Lysine.
Properties of amino acids 00:09:31
1. Exhibits D & L isomerism (L isomers are present in proteins)

(Except glycine which is optically inactive).
2. Aromatic AA absorb UV light (250 -290 nm) d/t presence of conjugate rings.
3. Exhibits buffering capacity :
1. Maximun when pH = pKa.
2. Maximum : Imidazole group of histidine (pKa = 6.4).
4. Zwitterions/ampholyte : pH = pI (isoelectric pH).
Amino acids to proteins 00:13:06
H H H H
NH3+- C -COOH + NH3+- C -COOH NH3+- C -CO NH - C -COOH
R R R R
Peptide bond :
• Uncharged & Polar.
• Partial double bond.
• “ Trans “ in nature.

Structure of proteins : ----- Active space -----
Primary • Linear sequence of AA.

structure • Peptide bonds (covalent) are involved.
• Not lost on denaturation.
Secondary α helix
:
structure • Right handed spiral.
• M/c & most stable structure.
• Intrachain hydrogen bond.
β sheet/β pleated : 2nd m/c.
• Zig zag/extended structure.
• Interchain hydrogen bond.
• Parallel/anti-parallel.
Tertiary 3D organization of single polypeptide.
structure Domain : Structure that performs task.
1. Rossmann fold : NAD (P)+ binding domain
present in oxidoreductase enzyme.
2. Immunoglobulin fold.
Quaternary • > 1 polypeptide.
structure • Subunit interaction.
Note :
• Secondary structure has turns (short segments) & loops (long segments).
• Amino acid that disrupts alpha helix : Proline.
• Amino acid that induces bends in alpha helix : Glycine.
• Motifs are supersecondary structures.
Protein folding 00:19:42
Auxillary proteins that assist protein folding : Molecular chaperones (heat shock
proteins).
Eg :
• BiP (Immunoglobulin heavy chain binding protein).
• Glucose Regulated Protein (GRP-94).
• Calreticulin.
• Calnexin. Calcium binding proteins

34 05 Biochemistry

Protein misfolding diseases
Prion diseases Prion related protein diseases Amyloidosis
Prion related protein diseases :

1. Alzheimer’s disease.
2. Parkinson’s disease.
3. Beta thalassemia.
4. Cystic fibrosis.
5. Huntington’s disease.
6. Fronto Temporal Dementia (FTD).
7. Amyotrophic Lateral Sclerosis (ALS).
8. Dementia with Lewy Bodies (DLB).
Protein degradation :
Lysosomal degradation Proteasomal degradation

ATP independent process ATP dependent process
Long-lived proteins Short-lived proteins
Membrane proteins Misfolded proteins
Note :
• Proline (P) glutamate (E) Serine (S) Threonine (T) : PEST.
• PEST sequence is needed for proteasomal degradation.
• PEST + Ubiquitin → protein degradation.
• Process is called “ kiss of death “.
Collagen 00:24:56
• Most abundant protein in human.

• Most abundant extracellular protein.
• Major type of collagen in bone : Type I.
• Most abundant type of collagen : Type I.
• Major type of collagen in cartilage : Type II.
• Major type of collagen in microfibrils : Type VI.
• Major type of collagen in basement membrane of kidney : Type IV.

Structure of collagen : ----- Active space -----

( Gly-X-Y..... Gly-X-Y)1000
• X - Hydroxyproline. → →
• Y - Hydroxylysine.
Most abundant amino acid : Glycine.
3 Alpha domains
Recurring amino acid : Glycine. Alpha chain
turn in right handed
Triple helix
Left handed right handed
direction
Quarter Staggered structure (side to side Triple helix : 1/4th distance) :
1/4th
1/4th
lysyl & hydroxylysyl Lysyl oxidase Covalent cross

linking sed tensile strength
residues Copper
Synthesis of collagen :
Intracellular Extracellular
Place RER of Fibroblast Extracelluar matrix
Product Procollagen Tropocollagen
formed
Major 1. Hydroxylation : 1. Cleavage.
events • Prolyl & lysyl hydroxylase. 2. Quarter staggered
• Requires Vit-C. structure
• Facilitates triple helix. 3. Covalent cross links : By
2. Glycosylation : Aldol condensation (requires
• Hydroxylysyl residues. Cu).
3. Triple helix formation :
• 3α chains join

36 05 Biochemistry

Diseases associated with collagen :
Type of collagen Disease associated
affected
Type 1 Osteogenesis imperfecta
Osteoporosis
EDS type VII
Type II Severe chondrodysplasias
Osteoarthritis
Type III EDS type IV
Type IV Alports syndrome
Type VI Bethlem myopathy
Type VII Epidermolysis bullosa, dystrophic
Type 10 Schmid metaphyseal dysplasia
Applied aspects - General amino acid metabolism 00:35:24
Ketoacids Biologically
Amino acid imp Amines
NH3 CO2
Handling of amino group :

I. Transamination :
α Amino acid α keto acid
PLP / B6 Transaminase
α keto acid α Amino acid
Alanine α ketoglutarate Aspartate α ketoglutarate
PLP / B6 ALT PLP / B6 AST
Pyruvate Glutamate Oxaloacetate Glutamate
Site : Cytoplasm.
Characteristics :
• Reversible.
• Concentrate all amino group in AA as glutamate (non toxic).
• Ping pong mechanism.
• AST & ALT : Specific for substrate AA, non specifc for alpha keto glutarate.

II. Transport of amino group : ----- Active space -----
any α Amino acid α ketoglutarate
any α keto acid Glutamate

Glutamine First line
Purine
synthetase +NH3 pyramidine trapping of
Porphyrines ammonia
Glutamine
Note :
• Glutamine is transport form of ammonia in most organs except in muscle
(alanine).
• Glutamic acid on decarboxylation : GABA.
• Glutamic acid on deamination : Alpha Ketoglutarate.
III. Oxidative deamination :

Liver
Alanine
Glutamate
Glutamine
Glutamate Dehydrogenase
NH3 Urea cycle

NAD(P) +
NAD(P)H
NOTE : α ketoglutarate
Liver GDH is allosterically :
• Activated by : ADP.
• Inhibited by : ATP, GTP & NADH .
Urea/ornithine cycle/Kreb’s Henseleit cycle 00:43:51
Organ : Liver.
Organelles : Cytoplasm, mitochondria.
Respiratory CO2
NH2- CO -NH2 Aspartate from TCA

NH3

38 05 Biochemistry
----- Active space ----- Mitochondria Cytoplasm
Co + NH3
2
2 ATP Aspartate
CPS-I (RLS)
2 ADP
Carbamoyl Phosphate “CITRIN”
OTC
Citrulline
Ornithine
Citrulline + Aspartate
I ATP
Ornithine
Transporter 2 Pi Argininosuccinate Synthase
I AMP
Argininosuccinate [AS]
Ornithine
H 2O AS lyase
Urea Arginase Arginine
Fumarate TCA cycle
• Rate limiting step (RLS) : CPS I.
• Allosteric activators of above step : N - Acetyl glutamate.
Urea cycle disorders :

Disease Enzyme defect
Hyperammonemia type 1 CPS- 1 (Carbamoyl Phospate Synthetase)
Hyperammonemia type II OTC (Ornithine Transcarbamylase)
HHH syndrome Ornithine transporter
(Hyperammonemia
Hyperornithinemia
Homocitrullinemia)
Citrullinemia type I Arginiosuccinate synthetase
Citrullinemia type II Citrin transporter
Argininosuccinic aciduria Arginiosuccinate Lyase
Argininemia Arginase

Hyperammonemia type 2 : M/c urea cycle defect. ----- Active space -----
Carbamoyl phosphate
Defect in OTC accumulation Seeps into cytoplasm
Orotic aciduria Orotic acid synthesis
Excretion of Pyrimidine synthesis

pyrimidine in urine
Diagnosis of urea cycle disorders :
Blood NH3
Check blood pH
Increased Decreased
Urea cycle D/o Organic aciduria
Specific AA Non specific AA
Plasma orotic Acid

• Citrulline : Citrullinemia. Increased Normal
• Ornithine : HHH syndrome.
• Arginine : Argininemia. Hyperammonemia Hyperammonemia
• Arginosuccinate : Arginino- type 2 type 1
succinic aciduria.
Note :
• AA that do not undergo transamination :
a. Proline.
b. Hydroxyproline.
c. Threonine.
d. Lysine.
• Amino acid that increases in plasma during starvation : Alanine.
• AA that increases in plasma during hyperammonemia : Glutamine.

40 06 Biochemistry
Phenylalanine & Tyrosine 00:00:22
PAH
Phenylalanine Tyrosine
Tyrosine
transaminase
Catabolic Anabolic
Tyrosinase
Tyrosinase hydroxylase
Ketogenic Glucogenic Thyroid Catecholamines

Melanin hormones
Phenylalanine 1 Tyrosine 4
hydroxylase transaminase PHPP (para
Phenylalanine Tyrosine hydroxy phenyl
pyruvate
GTP BH4 BH2 PHPP 5
3 hydroxylase
Dihydrobiopterin or 4-HPPD
NADP+ reductase NADPH + H+
Homogentisate
2
Homogentisate
oxidase 6
BH2 : Dihydrobiopterin Maleylacetoactetate (MAA)

BH4 : Tetrahydrobiopterin MAA cistrans
isomerase
Fumaryl acetoacetate (FAA)
7
FAA hydrolase
Fumarate Acetoacetate
Disorder Defective enzyme

1 Classical phenylketonuria (PKU) Phenylalanine hydroxylase (PAH)
2 Non classical PKU (type 2 & 3 ) Dihydrobiopterin reductase
3 Non classical PKU (type 4 & 5 ) Defect in synthesis of BH 4
4 Tyrosinemia type 2 Tyrosine transaminase
5 Neonatal/ Type 3 Tyrosinemia PHPP hydroxylase/ 4-HPPD (4 hydroxy
phenyl pyruvate dioxygenase)
6 Alkaptonuria Homogentisate oxidase
7 Type 1/ Hereditary/ Hepatorenal Fumaryl acetoacetate (FAA) hydrolase
Tyrosinemia
Phenylketonuria : 00:08:11 ----- Active space -----
M/c metabolic disorder a/w amino acids.

Biochemical defect in Phenylalanine hydroxylase leads to :
• Increased Phenylalanine which further enters alternate pathways to form
ketoacids like Phenyl lactate & Phenylacetate.
Phenylacetate causes mousy body odour.
• ↓ in Tyrosine → ↓ in Melanin, Catecholamines, Thyroid hormones →
Hypopigmentation (Fair skin + blonde hair), Neurological deficits (agitated &
mentally retarded).
C/f also includes intractable vomiting.
Investigations :
1. Guthrie’s test positive/bacterial inhibition test- (Bacillus subtilis culture
2. Ferric chloride test. shows increased growth)
3. Blood phenylalanine. (N = 2-6 mg/dl)
4. Enzyme studies.
5. Genetic mutation studies.
Treatment :
• Phenylalanine restricted diet.
• Synthetic cofactor BH4 (Sapropterin dihydrochloride).
• Concentrate of large neutral amino acid (LNAA).
Alkaptonuria : 00:12:35
Biochemical defect in homogentisate oxidase (aka homo- Garrod’s Tetrad

gentisate dioxygenase or dihydroxyphenylaceto dioxygen- Cystinuria.
ase) leads to : Alkaptonuria.
• Increase in levels of Homogentisate → polymerises to Albinism.
Benzoquinoacetate. Pentosuria.
Skin & sclera Intervertebral disc Excreted through kidney
Black Ochronosis Black discoloration of urine on

pigmentation (low back pain) standing/ on alkalanisation.
No mental retardation or neurological deficit occurs here.

Onset : Middle age

42 06 Biochemistry

Investigations :
• Ferric chloride test.
• Silver nitrate test.
• X-ray spine : Bamboo-like spine/ parrot beak appearance .
Treatment :
• Nitisinone (inhibits PHPP hydroxylase → Homogentisate accumulation).
Anabolic Fate of Phenylalanine :

1. Catecholamines :
Site : Chromaffin cells of adrenal (epinephrine) & extra-adrenal (norepineph-
rine).
(RLE)
Tyrosine Dopa B6 Dopamine
Tyrosine hydroxylase DOPA decarboxylase
Dopamine beta-oxidase
Nor- Norepinephrine
metanephrine
Vanillyl SAM Methionine
Degradation by
mandelic COMT/ MAO SAH
acid
Metanephrine Epinephrine
RLE : Rate limiting enzyme
Pheochromocytoma :
• Tumor of adrenal medulla → Catecholamines.
• Produces a triad of symptoms (Palpitations + headache + sweating).
• Fluctuating HTN can also be seen.
• Investigation : Plasma/Urine metanephrines & VMA (levels increased).
2. Melanin :
Site : Melanosomes in melanocyte (stratum corneum).
RLE
Tyrosinase Tyrosinase
Tyrosine DOPA Dopaquinone Melanin
Albinism :
Metabolic defect of Tyrosinase leads to inability of melanin synthesis.
C/f : Milky white hair & skin, Lacrimatio, Photophobia.

Tryptophan 00:20:12 ----- Active space -----
Tryptophan
Tryptophan pyrrolase
Catabolic Tryptophan Anabolic

hydroxylase Quinolinate phospho-
ribosyl transferase
Serotonin (QPRTase)
Ketone bodies Glucose
Melatonin NAD+ (vitamin B3)
Catabolic fate :
Tryptophan Tryptophan N. formyl kynurenine
pyrrolase
THFA
Formyl THFA
Kynurenine
Kynurenine hydroxylase
3-OH kynurenine
Kynureninase
(cofactor : PLP)
RLE
3-OH anthranilate NAD+
QPRTase (vit. B3)
• Tryptophan pyrrolase contains Heme, thus deficient in low heme states.
• Pyridoxal Phosphate deficiency → B3 (Niacin) def → Pellagra like symptoms.
3-OH kynurenine enters alternate pathway to form Xanthurenic acid
(Excreted in Urine).
Anabolic fate :
RLE
Tryptophan Decarboxylase 5-OH tryptamine
Tryptophan hydroxylase 5-OH Tryptophan
PLP (Serotonin)
B6 deficiency
Acetyl Serotonin
↓Dopamine, ↓Serotonin Methylation by
SAM
Neurotransmitter deficiency Melatonin
Pyridoxine dependent seizures in Children
Serotonin synthesized in Argentaffin cells of brain, platelets & GIT.

Melatonin synthesised in pineal gland.

44 06 Biochemistry

Carcinoid tumor :
• Tumor of Argentaffin cells (Argentaffinoma).
• Neuroendocrine tumor producing excess Serotonin.
Tryptophan
Serotonin NAD+
5-HIAA (in 24 hour urine) Flushing + diarrhea Pellagra like symptoms
Hartnup’s disease :
• BOAT 1 (transporter protein) not synthesised.
• Tryptophan accumulation in intestine → Release of indigo blue (indoxyl
compound) → Blue discolouration of diaper.
• Trytophan → serotonin (neurological deficits - intermittent ataxia)
+ NAD+ (Pellagra like symptoms).
• Investigation : Obermeyer test.
• Treatment : Lipid soluble esters of tryptophan.
Methionine and Cystiene 00:30:52
Methionine adenosine
Methione transferase SAM
N5
Methyl B12 Homocysteine methyl
B12 transferase/ CH3
Methyl methionine synthase
THFA B12
Adenosine
S adenosine
Homocysteine homocysteine
B6 + Serine
Cystathionine b synthase
Cystathionine • Methionine → SAM : Transmethylation

B6 Cystathionase
(SAM : Principle methyl donor).
• Homocysteine → Homoserine + Cysteine
Homoserine + Cystiene : Trans-sulfuration.
Disorder Defect in
Methionine adenosine transferase (MAT)
Hypermethioninemia
Boiled cabbage odour.
Classic Homocystinuria Cystathionine b synthase.
Cystathioninuria Cystathionase.
Non classic homocystinuria N5 methyl THFA / Methyl B12 formation.
Folate trap : ----- Active space -----

Deficiency of B12 → ↑ N5 methyl THFA → THFA starvation/ folate trap.
Cystinuria :
Defect in di-basic amino acid transporter(mnemonic: COLA)
(Cystine, Ornithine, Lysine, Arginine) → Excreted from kidneys as a dipeptide.
Cystinosis : LSD (lysosomal storage disorder).

Defect in cystinosin → Accumulation of cystine in lysosomes→ Liver failure, kid-
ney failure, bone marrow suppression, corneal opacity (multi-system disorders).
Branched chain amino acids (BCAA) 00:37:57
BCAA
1. Leucine Transamination
2. Isoleucine
Branched chain ketoacid
3. Valine NAD+ BCKA dehydrogenase (similar to
NADH pyruvate dehydrogenase)
BCKA : Branched Chain Keto Acid Acyl coA + CO2
Maple syrup urine disease :

• Defect of BCkA dehydrogenase.
• C/f : Failure to thrive, lethargy, convulsions, floppy baby with bouts of
hypertonia + hypotonia (boxing movements) + maple syrup/ burnt sugar or
caramel odor.
• Excretion of BCKA + excretion of leucine, isoleucine and valine.
• Investigation : Urine positive for Rothera’s test.
• Treatment : Thiamine supplementation (co-enzyme for BCKA
dehydrogenase).
Glycine 00:40:40
Products :
• Glycine + arginine + methionine → Creatine.
• Glycine + succinyl coA --→ Heme → Contributes to C4, C5, N7 of purine.
• Conjugation of bile acid (also conjugated by taurine).
• Conjugation of benzoic acid to form hippuric acid.
• Glutamic acid + cysteine + glycine → g glutamyl cysteinyl glycine (glutathione)
Functions as a neurotransmitter.
46 06 Biochemistry

Glutathione : Glutathione
• Atypical/ pseudopepeptide. peroxidase
• Active group : SH group of cysteine. H2O2 GSH NADP+
Functions : H2O GSSG NADPH
• Amino acid transport in brain, intestine, kidneys. Glutathione
• Conjugation of phase 2 of xenobiotic reaction. reductase
• Free radical scavenger (H2O2 → H2O).
Erythrocytic glutathione reductase (flavoprotein) : Indicates riboflavin/ B2 status
Serine 00:44:42
Used to synthesise :
• Cysteine. Metabolic function : CoA
• Phosphatidyl serine. Taurine
Glutathione
• Precursor amino acid for selenocysteine.
Decarboxylation Methylation
• Serine Ethanolamine Choline & Betaine.
Arginine 00:46:06
Used to synthesise : NADPH required

• Nitric oxide (EDRF).
• Agmantine ArginineNO synthase Citrulline
• Urea O2 NO
• Ornithine
Summary :
Disorder Defective enzyme
Albinism Tyrosinase
MSUD BCKD
Isovaleric aciduria Isovaleryl coA dehydrogenase
Homocystinuria Cystathionine beta synthase
Phenylketonuria (PKU) Phenylalanine hydroxylase
Alkaptonuria Homogentisate oxidase
Tyrosinemia type 1 Fumaryl acetoacetate hydrolase (FAA)
Tyrosinemia type 2 Tyrosine transaminase
Tyrosinemia type 3 PHPP

Laboratory tests in aminoacidurias : ----- Active space -----

Test Disease
Ferric chloride Test PKU/ Alkaptonuria
Dinitropheny| hydrazine test, Rothera’s test MSUD
Guthrie test PKU
Obermeyer Test Hartnup disease
Cyanide nitroprusside test Homocystinuria
La Brosse VMA spot test Pheochromocytoma
5 HIAA Carcinoid syndrome
Inborn errors of amino acid metabolism disorders associated with peculiar odor :
Test Odour associated
Glutaric acidemia (type Il) Sweaty feet
Hawkinsinuria Swimming pool odor
Isovaleric acidemia Sweaty feet
MSUD Burnt sugar/Maple syrup/caramel
Hypermethioninemia Boiled cabbage
Multiple carboxylase deficiency Tomcat urine
Oasthouse urine disease Hops-like
Phenylketonuria Mousy or musty
Trimethylaminuria/ Fish odour syndrome Rotting fish
Tyrosinemia/Type 1 Boiled cabbage, rancid butter
Homocystinuria :
• C/f : Ectopia lentis (down + medial), pectus excavatum, skeletal deformities,
elongated fingers (arychnodactyly), scoliosis, mental retardation.
• Prone to thromboembolism (CVD or CAD).
• Inv. : Cyanide nitroprusside test.
Cyanide nitroprusside test Arachynodactyly
Ectopia lentis Pectus excavatum Scoliosis Knee deformity

48 06 Biochemistry

Type 2 Tyrosinemia (Oculo cutaneous syndrome/ Richner Hanhart syndrome) :
Hyperkeratotic, non
pruritic plaques on
soles of foot
(oculo-cutaneous).
Corneal ulcer
Alkaptonuria :
• No mental retardation
Blackish Urine turning

discoloration black
of pinna
MSUD :
Hypotonia + DNPH test
bouts of positive
hypertonia.
Porphyrias 00:53:16
Test Defective enzyme

ALA dehydratase deficient ALA dehydratase
porphyria (ADP)/ plumbopor- Enzyme inhibited by lead. No
phyria Lead poisoning : Urine ALA accumulation photo
sensi-
Acute intermittent porphyria PBG deaminase/ HMB synthase/
tivity
(AIP)(M/c acute porphyria) Uroporphyrinogen 1 synthas
Congenital erythropoietic Uroporphyrinogen 3 synthase (UROS)
porphyria (AR)
Porphyria cutanea tarda Uroporphyrinogen decarboxylase (UROD) Cuta-
(M/c porphyria) neous
photo
Hereditary coproporphyria Coproporphyrinogen oxidase
sensi-
Variegate porphyria Protoporphyrinogen oxidase C tivity
Erythropoietic proto porphyria Ferrochelatase (FeCh)
(AR)

Molecular biology 00:00:14
Chemistry of Nucleic acid :
• Purines :
Purine Adenine Guanine

(6-aminopurine) (2-amino-6-oxo group)
• Pyramidines (single ring) :
Deamination Methylation
Pyramidine
Cytosine Uracil Thymine
(2-oxo-4-amino pyrimidine) (2,4-dioxo pyrimidine) (2,4-dioxo-5-
methyl pyrimidine)
Nucleotide :
Phosphate Nitrogenous base

group
Ester bond β-N-glycocidic bond
Pentose sugar
Nucleotide
= Nitrogenous base + Pentose sugar.

Two Nucleotides are joined by 3I-5I Phosphodiester bond.

50 07 Biochemistry
Purines 00:03:20
De novo synthesis of purines :

Occurs almost everywhere, except brain, leukocytes & erythrocytes
(only depend on the salvage pathway).
PRPP synthetase Phospho ribosyl

Ribose 5 phosphate
pyrophosphate (PRPP)
ATP AMP
H2O
Glutamine
PPi
PRPP glutamyl (Rate limiting
Glutamate enzyme)
AMP amidotransferase
Inosine monophosphate →----- Phospho ribosyl amine
GMP
Salvage pathway 00:06:32
Hypoxanthine/ Guanine HGPRTase

IMP/ GMP
PRPP PPi
Adenine APRTase
AMP
PRPP PPi
Kinases
Adenosine/ guanosine AMP/ GMP
ATP AMP
• Nitrogenous bases are recycled → Nucleotides.
Lesch Nyhan syndrome :

• Complete Deficiency : HGPRTase.
• Seen only in males (XLR).
• C/fw : Self mutilation, hyperuricemia.
Self mutilation

Purine catabolism 00:09:36 ----- Active space -----

B cells + T cells affected Only T cells affected
Inhibited by Allopurinol (Gout - suicide inhibition)

Gout :
• C/f : Hyperuricemia, uric acid nephrolithiasis, acute inflammatory arthritis.
• Acute gout : M/c site → 1st MTP joint
• Chronic gout : Subcutaneous nodules (tophi).
• Ix : Arthroscopy + synovial fluid examination
Needle shaped, Negatively birefringent monosodium
urate crystals on Polarised light microscopy.
Pyrimidines 00:11:58
Contributed by C
Site of synthesis : Glutamine N 3
4
5 C Contributed by
Liver (cytoplasm + mitochondria).
Donated by Aspartic acid
2 6 C
Respiratory CO2 C 1
Catabolism of : N
• Cytosine / Uracil → Beta alanine produced (soluble in water).

• Thymine → Beta amino isobutyrate (soluble in water).
Hereditary Orotic aciduria : (Autosomal recessive)

Defect in Denovo synthetic pathway of pyrimidine.
• C/f : Child with failure to thrive, macrocytic, hypochromic, megaloblastic
anemia (iron, Vit B9, vit B12 normal) + mental retardation.
• In Type l Enzyme defective : UMP synthase (bifunctional enzyme - OPRTase
+ OMP decarboxylase).
• In Type II Enzyme defective : Only OMP decarboxylase.

52 07 Biochemistry

Structure of DNA 00:15:36
Watson & crick model :

• ATGC Base pairing rule : A = T, G C (hydrogen bonds).
• Chargaff’s rule : A+G (purines) = C+T (pyrimidines).
• Right handed double helix.
Organization of DNA :
Double stranded DNA ( 1.75 turns/ 145 base pairs) + Histone.
Octamer (H2A, H2B, H3, H4 X 2) → Nucleosomes form a 10 nm chromatin fibril
(beads on string appearance d/t linker DNA with H1 histone) → 30 nm
chromatin (6-7 nucleosomes arranged circularly) → Condensed &
non-condensed loops → Metaphase chromosome.
DNA processes 00:19:33
DNA replication :
• Both strands act as template.
• 5’ → 3’ direction.
• Occurs in S phase (synthesis).
• Semidiscontinuous, semi-conservative.
• Requires primer.
Enzymes :
• Helicase : Unwinds the DNA.
• Topoisomerase : Nicking & resealing.
• Primase : Synthesis of RNA primer
• DNA polymerase
• DNA ligase : Seals the nicks
DNA Polymerases (prokaryotes) :

DNAP 1/ DNAP 2 DNAP 3
Klenowpolymerase/
Kornberg’s enzyme
DNA proofreading
DNA repair -
Gap filling - Synthesis of leading strand
Removal of primers - Synthesis of Okazaki fragments
Note : Klenow polymerase is DNAP 1 without the 5I-3I Exonuclease.

DNA Polymerases (eukaryotes) : ----- Active space -----
α β γ δ ξ
Primase ac- Major DNA repair Mitochondrial DNA Lagging strand Leading strand
tivity enzyme synthesis synthesis synthesis
- - Proofreading
Steps of DNA replication :

• Identify Ori (fixed point on DNA where replication begins) → Binds to
Ori-binding proteins → AT rich region unwinds → SSB (Single strand bind-
ing) proteins attach & prevents local reannealing of DNA → Helicase further
unwinds + Topoisomerase relieves torsion → Replication fork formed.
• Replication fork (DNA synthesis occurs here) → On Leading strand (RNA
primer synthesis by primase + DNAP 3 extends primer continuously) + while
on lagging strands (RNA primer synthesis by primase + Okazaki fragments
added by DNAP 3 - discontinuously).
• RNAs removed & gaps filled by DNAP1.
• Nicks ligated by DNA ligase.
OriC : E.coli Ori λ : Bacteriophage
Autonomous replicating sequence (ARS) : Yeast
Multiple Ori : In Humans
Origin of replication Lagging

Leading strand strand
Sliding Leading strand

clamp DNA template Overall direction
Polymerase III of replication
Single stranded
binding protein
Leading stran Continuous synthesis
Helicase
Replication fork
RNA primase Okazaki fragments
Parental DNA DNA Polymerase III
Topoisomerase/ RNA
gyrase primer
DNA DNA Ligase
sliding clamp
Lagging strand Polymerase I
template Lagging strand/ Ligase
discontinuous
synthesis

54 07 Biochemistry

Telomere & Telomerase :
Telomeres :
• Ends of the chromosomes.
• End replication error → Shortening of DNA → Hayflick limit → Causes
aging.
Telomerase/ terminal telomere transferase :

Parts :
• RNA template
• Reverse transcriptase activity.
Prevents shortening of DNA (No Hayflick limit).
Seen in stem cells, lymphocytes, cancer cells. Absent in somatic cells.
DNA repair defects :
DNA defect Repair mechanism Disorders associated

Double Strand Nonhomologous End • Severe Combined immunodeficiency
Breaks Joining (NHEJ) (SCID)
• Radiosensitive SCID
Single Strand Homologous • Ataxia Telengiectasia like disorder
Breaks Recombination (HR) • Nijmen Break Syndrome
• Blooms Syndrome
Intrastrand • Werner Syndrome
cross links • Rothmund thomson Syndrome
• Breast Cancer susceptibility (BRCA 1,
BRCA 2)
Bulky ad- Nucleotide excision • Xeroderma Pigmentosa (blisters in
ducts pyrim- repair (NER) sun-exposed areas + skin cancers).
idine dimers • Cockayne syndrome
(UV rays) • Trichothiodystrophy
Abasic sites Base excision repair • MUTYH-associated polyposis
(BER)
Bases mis- Mismatch repair • Hereditary non-polyposis colorectal
match (MMR) cancer (HNPCC/ Lynch syndrome).

Mitochondrial DNA 00:33:33 ----- Active space -----

• Ds circular DNA
• 16,569 base pairs.
• Function : Codes for 13 proteins in ETC (19% proteins)
Nuclear v/s mitochondrial codons :

Nuclear DNA Mitochondrial DNA
AUA Isoleucine Methionine
UGA Stop codon Tryptophan
AGA, AGG Arginine Stop codons
• High rates of mutations as no introns/no protective Histones/repair enzymes
& is exposed to O2 free radicals.
• Cytoplasmic/ matrilinear inheritance (non-Mendelian).
• Heteroplasmy.
DNA Transcription : 00:36:31

• Conversion of DNA to RNA.
• 2 strands : Template & Coding.
• No primer required.
• Sequence in RNA is always in 5’ to 3’ direction, complementary to template
but same as coding strand (except Thymine - replaced by Uracil).
Promoters :
Sequences which specify start sites (+1) of transcription.
Upstream Start site Downstream
• Prokaryotes : Pribnowbox , TGG box

• Eukaryotes : TATA box , CAAT box.
Enzymes of transciption (polymerases) :
In eukaryotes :
RNAP 1 RNAP 2 RNAP 3
rRNA (most abundant) mRNA, miRNA, SnRNA, long tRNA, 5sRNA
noncoding RNA

56 07 Biochemistry

Post transcriptional modifications : 00:40:31
mRNA in prokaryotes does not undergo post transcriptional modifications.

Steps :
1. Capping (7-methyl guanosine) at 5’ end.
2. Poly A tailing (40-200) at 3’ end.
3. Splicing of exons & removal of introns by spliceosomes.
SnRNPs Primary transcript

(SnRNA+Ribonucleo protein)
4. Alternate RNA splicing
RNA editing : 00:43:16
In liver : In intestines :
ApoB gene ApoB gene
ApoB mRNA ApoB mRNA (codon called CAA → Cyto-

sine deaminated to Uracil)
ApoB 100
UAA (stop codon)
Truncated protein (ApoB 48)
Types of RNA 00:44:33
miRNA (micro) & siRNA (silencing) :

Single stranded, small, non-coding RNA with 2l-22 nucleotides
miRNA :
• Endogenously sythesised
• 3’ UTR of mRNA is bound with mi RNA → mRNA degraded or translation ar-
rests → Gene knockdown/RNA interference (post transcriptional regulation).
• Regulates gene expression.
siRNA :
• Exogenously synthesised.
Transfer RNA (tRNA) :

Small RNA with intra-strand base pairing (clover leaf shape).

Secondary structure of tRNA : ----- Active space -----

Recognises specific amino acyl tRNA synthetase
Binds to specific amino acid
Binds to ribosomal assembly
Binds to specific codon

Ribosomal RNA (rRNA) :
• Structural function.
• Types : 28S, 18S, 5.8S, 5S
• Eukaryotes : 80S (40S + 60S)
• Most abundant RNA
Translation 00:51:00
RNA → Protein (Occurs in ribosomes).

Genetic code :
• Triplet codon (3 nucleotides).
• Universal (exception : mitochondrial DNA).
• Unambiguous.
• Start codon : AUG (Eukaryotes : Methionine, Prokaryotes : formyl methionine)
• Degenerate (in 3rd base).
• Non-overlapping.
• Stop codon : UGA, UAG, UAA.
Steps of translation :
1. Charging of tRNA (aminoacyl tRNA synthetase) → Uses 2 iPO4
2. Initiation (80S ribosomes) → Has 3 sites E,P,A.
Start codon : AUG → Methionine. Starts from P-site.
3. Elongation : Binding of new Aminoacyl tRNA at A-site (EF 1 & ATP are
required) + Peptide bond formation (by peptidyl transferase, 28S rRNA, 60S
rRNA, no ATP required) + Translocation of ribosome on mRNA (EF2 + GTP are
required) to free the A-site for next amino acid.
4. Termination (releasing factor + GTP required).
58 08 Biochemistry
Molecular biology techniques 00:00:16
Hybridization techniques :
1. Blotting techniques :
Gel electrophoresis Transfer to nylon/ Add probe :

Southern blot : DNA. nitrocellulose paper Southern blot : DNA.
Northern blot : RNA. Northern blot : cDNA.
Western blot : Protein. Western blot : Antibody.
Detection : Image specific

Southern blot : Specific DNA. probe binding
Northern blot : Specific RNA.
Western blot : Specific antibody.
• cDNA : Produced from RNA by using reverse transcriptase.

• Southwestern blot : DNA - protein interaction.
2. Microarray :
Types :
a. DNA microarray.
b. cDNA microarray : Study of gene expression.
c. Protein microarray.

Array comparative genomic hybridisation (CGH) : ----- Active space -----
Karyotyping 00:11:06
Steps of karyotyping :

60 08 Biochemistry
----- Active space ----- Banding techniques :

Banding technique Uses
Giemsa (G) Light and dark reproducible pattern.
Quinacrine (Q) • Similar to Giemsa.
• Examination with a UV fluorescence microscope.
• Chromosome are denatured.
Reverse (R)
• Light and dark bands in reverse pattern.
Centromeric (C ) Heterochromatin regions are stained preferentially
Human genome project :
Notable results :
• Exons : 1. 10 % (~ 1.5 %).
• No of protein coding genes : 30,000 to 40,000 (20,000 presently).
• Average gene Length : 3000 bp (base pair).
• No of proteins : 80000 to 100000.
• Human genome : 3.2 billion base pairs in a haploid set of chromosomes.
FISH (Fluorescence in situ hybridization) :

• Simple detection of genetic element in a morphologically intact cell.
• Uses 5 fluorophores (23 distinct mixtures).
• Spectral karyotyping (SKy).
Applications :
1. To study micro gene deletion.
2. To study gene amplification.
3. Numerical & structural abnormalities.
4. Mapping of gene.
Recombinant DNA technology 00:19:28
In vivo amplification.
1. Restriction endonucleases :
• Cut ds-DNA at specific palindromic site (Molecular scissors).
• Uses :
a. To restrict entry of phages in bacteria.
b. Used as molecular scissors in recombinant technology.
2. Vectors : Carriers of foreign DNA or target DNA.

Vectors Types ----- Active space -----
Natural a. Plasmid :
• Extrachromosomal ds circular DNA in bacteria
(0.1-10 kbp).
• Provide antibiotic resisitance.
b. Phage DNA : Linear DNA (10-20 kbp).
c. Cosmid : Plasmids with cosgene (30-50 Kbp)
Artificial a. BAC (Bacterial artificial chromosome).
300-500 Kbp
b. PAC (Phage artificial chromosome).
c. YAC (Yeast artificial chromosome) → 1000-3000 Kbp.

62 08 Biochemistry

Restriction Fragment Length Polymorphism (RFLP) :
DNA fingerprinting 00:26:39
Used in medicolegal
cases (paternity dispute).
DNA footprinting :
Enzyme : DNAse.

Polymerase Chain Reaction (PCR) 00:31:12 ----- Active space -----
Components :
• DNA sample.
• Primers.
• Nucleotides.
• Taq polymerase.
• Mix buffer.
• PCR tube.
• Thermal cycler.
Steps :
1. Denaturation.
2. Annealing : Primers are added.
3. Extension :
Taq polymerase + nucleotides added.
Flanking region : DNA sequence that is adjacent to the target DNA on either end.
Variants of PCR :
a. Reverse transcription polymerase chain reaction (RT-PCR) :
Amplification of RNA.
b. Real time PCR :
• Aka q PCR.
• Quantitative PCR.
• Amplification & detection simultaneously.
Genome editing : CRISPR cas 9 00:36:35
Bacterial defence mechanism.

CRISPR : Long interspersed region.
cas 9 : Endonuclease.

64 08 Biochemistry
DNA sequencing 00:39:27
Sanger’s sequencing : Pyrosequencing :

aka controlled chain termination. • DNA sequencing technique.
Most widely accepted. • Principle : Bioluminescence.
Components : • Enzyme : Luciferase.
• Di-deoxynucleotide (dd NTP) : Chain termination.
• Klenow polymerase.
Next generation sequencing :

Used for heterogeneous samples of DNA (population study).
Steps :
1. Spatial separation : Arrange in different spaces.
2. Amplification of these DNA in each of the space.
3. Massive sequencing simultaneously.
Droplet digital PCR 00:52:46
• Multiple fluorescence detected at the

same time in different droplets.
• More sensitive than traditional PCR.
Positive droplets : Those with target DNA.
Negative droplets : Those without target DNA.
ChIP (Chromatin Immuno Precipitation) : Chip = DNA microarray.

BIOCHEMISTRY REVISION-9 ----- Active space -----
Fat soluble : A , D , E , K
Vitamins
Water soluble : B , C
Endogenously synthesized : Vit D & B3 (Humans)
Vit K , Biotin , Pantothenic acid ( Bacterial flora )
Vitamin A 00:01:25
Carotenoids Retinoids
Pro Vitamin A Related to retinol
b carotene Retinal : 11-cis retinal + opsoin (Rhodopsin) in vision
( Plant source ) Retinol : Reproduction
Retinoic acid : Cell growth & differentiation
Vitamin A Metabolism :
• Richest source : Halibut liver oil
• Intestine : b carotene Dioxygenase Retinol → Retinyl Ester → Loaded to
Chylomicrons
• Liver : Stored as Retinyl palmitate ( in Perisinusoidal stellate cells of Ito )
• Transport proteins in blood : Transthyretin , Retinol Binding Protein (RBP)
• Reaction used for Vitamin A assay : Carr & Price reaction.
Vitamin A Deficiency
Organ Features
Eyes Earliest : Loss of vision to green light
1st symptom : Night blindness
Conjunctival xerosis , Bitot’s spots
Corneal xerosis →Keratomalacia →
Corneal ulcer → Opacity Bitot’s spots
Skin Keratinisation
Follicular hyperkeratosis :
Phrynoderma ( Toad skin )
Mucosa Squamous metaplasia of mucus secreting epithelium.
Tongue Loss of taste sensation (also seen in Zn deficiency )

66 09 Biochemistry

Vitamin A toxicity Vitamin A in Treatment
• Pseudotumor cerebri • b Carotene : Cutaneous porphyria, Psoriasis.
• Hepatomegaly, Cirrhosis • All trans retinoic acid : Promyelocytic leukemia
• Pathological # (Differentiation therapy )
• Teratogenic • 13 cis retinoic acid : Cystic acne.
Vitamin D 00:12:30
7- Dehydrocholesterol Dietary source

(Skin) Animals Plants (Ergosterol-D2)
UV-B
Cholecalciferol (D3)
25 hydroxylase (liver)
ss 25-OH Cholecalciferol
ce PTH
ex
24,25 di OH cholecalciferol (+)
1α hydroxylase (kidney)
Calcitroic acid
(Biologically inactive)
(Rate limiting step)
1,25-di OH Cholecalciferol , Calcitriol (Biologically active)
Vitamin D deficiency :
Inadequate mineralisation : Excess unmineralised osteoid.
• Before epiphysis closure : Rickets.
• After apiphysis closure : Osteomalacia.
Biochemical changes in nutritional rickets :

1,25 di OH Vit D & 25 OH Vit D S. Ca
PTH ( 2o Hyperparathyroidism)
1a hydroxylation Normalise S. Ca Phosphaturia :

Normalise / 1,25 di OH vit D Phosphate
Clinical features :
Windswept deformity
Fraying
Cupping
Growth plate
widening
Bowing

Richest source : Halibut liver oil ----- Active space -----

Best screening test : 25 OH cholecalciferol.
Vitamin D toxicity (Toxic dose in infants : 50 mcg / day)

• Contraction of blood vessels , High BP
• Calcinosis
Vitamin E & Vitamin K 00:21:56
Vit. Form Function

Vit. E a Tocopherol Most potent natural antioxidant
Protects : LDL & PUFA
Vit. K K1-Phylloquinone (diet) Post translational g carboxylation (Biotin

K2-Menaquinone (Bacterial flora) independent) of : C.F 2,7,9, 10/Protein C,S/
K3-Menadione(Synthetic/water soluble) Osteocalcin/Nephrocalcin.
Deficiency & Toxicity :
Vitamin Deficiency Toxicity

Vitamin E Spinocerebellar ataxia Platelet aggregation
Peripheral neuropathy
Hemolytic anemia
Vitamin K Bleeding manifestations Hemolysis → Hyperbilirubinemia
PT , BT Kernicterus
Vitamin B & C 00:27:02
Vitamin Active form & function Deficiency

Thiamine TPP (Coenzyme) Alcoholics
(Vit B1 ) Mutienzyme complex : Wet Beriberi : High output heart failure
• Pyruvate Dry Beriberi : PNS & CNS.
dehydrogenase Wernicke’s encephalopathy : Confusion
• a ketoglutarate + Ataxia + Ophthalmoplegia +
dehydrogense Nystagmus ( horizontal )
• Branched chain keto Wernickes-Korsakoffs Syndrome :
acid Above C/f + amnesia + Confabulatory
dehydrogenase psychosis
Transketolase
68 09 Biochemistry
----- Active space ----- Vitamin Active form Deficiency

Ribo FAD /FMN Cheilosis , Magenta tongue.
flavin • Acyl CoA Corneal vascularisation.
dehydrogenase Cystoid macular edema.
(B2)
• Succinate
dehydrogenase
Niacin NAD /NADP+
+
Pellagra (4 Ds)
(B3) Dermatitis (photosensitive) : Casal’s necklace
Dementia, depressive psychosis
Diarrhea
Death (advanced cases)
Corneal vascularisation Magenta tongue Casal’s necklace Gauntlet of pellagra

Indicator for Thiamine deficiency : Erythrocyte transketolase.
Indicator for Riboflavin deficiency : Erythrocyte Glutathione reductase
Causes of Niacin deficiency :
• Vit B6 deficiency
• Diet rich in Sorghum ( high leucine content )/ Maize (bound form )
Niacin toxicity
• Flushing (PG mediated ) →Mx: Pretreatment with Aspirin , Laropiprant (PG -)
• Hepatotoxicity.
• Glucose Intolerance , Hyperuricemia.
• Macular edema.
Other B Complex Vitamins 00:35:52
Vitamin Active form & Co enzymes Deficiency/toxicity

Pyridoxine PLP Deficiency
(Vit B6) • Transamination • Pellagra like symtoms.
• Decarboxylation • Peripheral neuropathy.
• ALA synthase • Convulsions.
• Glycogen phosphorylase • Anemia(Microcytic/sideroblastic)
• Oxaluria, Homocystinuria
• Xanthurenic aciduria
Toxicity : Sensory Neuropathy
Pantothenic CoA Gopalan’ s Burning foot syndrome /
Acid ( B5 ) Nutritional Melalgia

Folic acid THFA : One carbon metabolism. Seen in strict non vegans. ----- Active space -----
(B9) Enzyme : Homocysteine 1. Megaloblastic anemia
methyl transferase. 2. Homocysteinemia
3. Neural tube defects
Enzyme : Seen in Strict vegans.
• Adenosyl B12/Methyl B12 1. Megaloblastic anemia
• Methyl malonyl CoA 2. Homocysteinemia
Cobalamin
mutase. 3. Methyl malonic aciduria
( B12)
• Homocysteine methyl 4. Sub Acute Combined Degeneration (SACD)
transferase 5. B/L peripheral neuropathy
Vitamin C :
Function : Hydroxylation of lysine & proline (collagen triple helix).
Deficiency :
• Scurvy
• Follicular hyperkeratosis
• Scorbutic rosary
• Pseudoparalysis
• Barlow’s syndrome (<6 month infants)
Toxicity : Gastric irritation, Oxalate stones
Hemarthrosis Bleeding gums Splinter hemorrhages
Disorders of micronutrient metabolism 00:46:11
A. Copper metabolism :
Menke’s D/s
Wilson’s disease
(Kinky/ steely hair S/D)
AR XLR
ATP 7B gene ATP 7A gene
Cu excretion in intestinal cells
Cu excretion from liver cells
Defect in Xanthine oxidase &
Lysyl oxidase (collagen cross linking)

70 09 Biochemistry

Diagnosis of Wilson’s disease :
• S. Ceruloplasmin
• 24 hr urine Cu excretion
• Liver Cu assay : Gold std.
• Urine excretion of 3 methyl histidine
B. Iron metabolism :
Heme iron
Hepcidin
Heme transporter
Food Liver
iron Ferroportin
Fe3+ Duodenal Fe2+
Nonheme Cyt B
iron Fe3+
Fe2+
Ferritin Hephaestin Transferrin
DMT1
Lost by shedding of Erythroid

epithelial cells marrow
C. Selenium :
Deficiency of Selenium :
Antioxidant
Keshan disease :
Rich source : Brazil nut
• Endemic cardiomyopathy
Selenocysteine containing enzymes:
• China ( dietary def. )
• Thioredoxin reductase
Kashinbeck disease :
• Glutathione peroxidase
• Chronic joint d/s
• Deiodinase (Thyroid synthesis )
• Def. of Se & Iodine
• Selenoprotein P
D. Zinc :
Highest concentration in Hippocampus, Prostatic fluid.
Function :
• Metalloenzyme : Carbonic anhydrase,
Carboxypeptidase
• Stabilise human insulin.
• Spermatogenesis.
Zn deficiency :
• Hypogeusia
• Acrodermatitis enteropathica (AR) :
Perioral & perianal rash
Diarrhea, Rashes (Periorifacial)

E. Chromium : ----- Active space -----

Potentiate the action of insulin in patients with impaired glucose tolerance.
Chromium 6 : Stainless steel welding (pulmonary carcinogen).
F. RDA of important minerals :

Mineral RDA
Calcium Adult : 0.5 g , Children : 1g , Pregnancy : 1.5 g
Iron Male : 15-20 mg , Female : 20-25 mg , Pregnancy : 40-50mg
Iodine Male : 150-200 mcg , Female : 200-250 mcg
Energy from macronutrients 01:00:21
Macronutrients Energy (kCal/g )

Carbohydrates 4
Proteins 4
Fat 9
Alcohol 7
Note : Specific dynamic action/Thermic effect : Proteins > Carbohydrates > Fat.
Biochemistry of fed v/s fasting state 01:03:08
Organ Fed/Absorptive state Fasting

Pancreas Insulin : Glucagon ratio Insulin : Glucagon ratio
Glycogen synthesis Glycogenolysis
Liver Fatty acid synthesis Gluconeogenesis
TAG synthesis → VLDL Release of ketone bodies
Activation of HSL(Hormone Sensitive
Adipose Uptake of glucose
Lipase) : Lipolysis
tissue TAG synthesis
Glucose uptake Use fatty acids & ketone bodies

Muscle Glycogen synthesis Release aminoacids
Protein synthesis (substrate for gluconeogenesis)
Use glucose
Brain Glucose
& Ketone bodies

72 09 Biochemistry

Metabolic derangements in diabetes mellitus :
Insulin /Insulin resistance GLUT 4 activity
HSL Glucose uptake by

(Adipose tissue) Oxaloacetate
depleted peripheral tissues
Free fatty acids TCA cycle
b Oxidation X Gluconeogenesis
Acetyl CoA (liver)
Ketone body synthesis

Hyperglycemia
Ketosis
Biochemical tests 01:12:45
Name Test for Positive in

Reducing sugars
Benedict’s test Carbohydrates Homogentisate
Ascorbic acid
DKA (Benedicts’s +ve) ,
Rothera’s test Ketone bodies
Starvation (Benedicts’s -ve)
Heat & Acetic acid test Protein (Albumin) Nephrotic syndrome
Bile pigment
Fouchet’s test Obstructive jaundice
(Bilirubin)
Hay’s test Bile salts Obstructive jaundice
Urobilinogen Hemolytic Jaundice
Ehrlich test
Porphobilinogen Porphyria
Benedict’s test Rothera’s test Heat & acetic acid test
Fouchet’s test Hay’s test

Biochemistry Revision E6.5

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Biochemistry Revision E6.5

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Biochemistry Revision 1 01 1

BIOCHEMISTRY REVISION 1 ----- Active space -----

Enzymes are specialized proteins → Act as biological catalyst.

Simple enzyme Complex enzyme

Coenzyme : Cofactor : Prosthetic :

Classification of enzymes : 7 classes.

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

----- Active space ----- Class Class Name Definition Examples

Mechanism of enzyme action 00:15:05

Lowering of activation energy : (Activation energy = Difference between the

Mechanisms to lower activation energy :

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

Factors affecting enzyme activity 00:22:02

Line weaver burk plot/ Double reciprocal plot :

• Optimum temperature in humans : 35°- 40°C.

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Vmax remains constant. X-intercept moves towards zero.

Non competitive inhibition : Without Inhibitor

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

Uncompetitive inhibition : ----- Active space -----

Vmax decreases. X-intercept moves away from zero.

Uncompetitive Inhibition Noncompetitive Inhibition Competitive Inhibition

Enzyme regulation 00:41:44

Enzyme quantity Enzyme quality

Enzyme degradation Covalent Allosteric

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

----- Active space -----

Properties of allosteric enzymes :

Covalent modification/ hormonal regulation :

Et : Total enzyme concentration (E + Es).

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

BIOCHEMISTRY REVISION 2 ----- Active space -----

Introduction to carbohydrates 00:00:10

Carbohydrate : Aldose or keto derivative of polyhydroxyalcohol.

Glycosaminoglycans (GAG) 00:11:23

Unbranched polysaccharide containing repeating disaccharide units of Amino +

----- Active space -----

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

Glucose transporters 00:28:31 ----- Active space -----

Classified as : Sodium dependent (SGLT) & sodium independent (Glut)

High insulin : glucagon ratio Glut 2 in liver (high Km)

Glucose → Glucose 6 phosphate

Glycolysis/ EMP pathway 00:43:53

In all organs (site : cytoplasm). Both aerobic & anaerobically.

----- Active space -----

Dihydroxy acetonephosphate (DHAP) Glyceraldehyde 3 phosphate (G3P)

Pay off phase :

Gly 3 Po4 dehydrogenase Pi

1,3 Bisphosphoglycerate (1,3 BPG)

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

Important enzymes : ----- Active space -----

Pyruvate dehydrogenase 00:54:13

Significance of pyruvate dehydrogenase :

Clinical significance : (Leigh syndrome)

----- Active space ----- BIOCHEMISTRY REVISION 3

Glycogen metabolism 00:00:20

3. Conversion of glucose-1-PO4 to glucose

Anaerobic glycolysis 3 ATP

Factor favouring glycogen synthesis Factors favouring glycogenolysis

Biochemistry Revision • v1.0 • Marrow 6.5 • 2023

Glycogen Storage Disorders (GSD) 00:13:43 ----- Active space -----

Types Enzyme defect Clinical features

Liver GSD : Type I, III, VI, O.