Definition, types, Carbohydrate- Kreb's cycle, Glycolysis, Glycogenesis, Protein- Urea cycle, Lipids- Beta-oxidation, Abnormal metabolism of Carbohydrate, lipids, Protein diseases.

1. METABOLIS
(Normal & Abnormal)
Shalini N. Barad,
Assistant Professor,
Appasaheb Birnale College of Pharmacy.

2. • Metabolism: All biochemical changes that occur
in biological system are grouped together as
metabolism. OR
• Metabolism is the set of chemical reactions
(Anabolic & Catabolic) that occur in living
organisms to maintain life.
• Imp role played by it are as follow:
1) Chemical energy is obtained from fuel molecules.
2) Dietary nutrients are utilized as building block for
the synthesis of new molecule.
3) Building blocks are assembled into proteins,
nucleic acid, etc.
• It is of 2 type:- Catabolism & Anabolism

3. 1) Catabolism : It’s a process of degradation of
complex matter into simple form thus generating
energy & metabolites that provide metabolic fuel &
building block for the cell.
• During catabolism energy is released & conserved
in the form of ATP & NADH, NADPH & FADH2 &
rest is loss in the form of heat.

5. 2) Anabolism: It’s a biosynthetic phase, uses energy
to construct components of cells such as proteins
and nucleic acids.
• It require all energy input from ATP, NADH, etc.
• All the biochemical reaction of cell is catalyzed by
number of enzyme & other factor.
• Abnormal Metabolism: A metabolic disorder occurs
when the normal metabolism process fails due to
deficiency of enzymes Or other factor like Vit. &
minerals.
• It may be due to— genetic defect,
-- dietary deficiencies or
-- disease conditions

6. • Eg— In liver disease, the bile salt formation is
decreased which leads to lipid malabsorption
syndrome.
• Carbohydrate are most commonly used for
production of energy in all biological system.
• In Higher animal, carbohydrate are completely
oxidized to CO2 & H2O.
• This process require oxygen , hence it is known as
aerobic breakdown.
Carbohydrate Metabolism:--

7. • ATP & it metabolic role:
• The metabolic energy exchange is carried out
through common intermediate Adenosine
triphosphate (ATP).It is present in all living cell.
• It has strong tendency to hydrolyze to ADP & PO4,
during this energy is liberated & make available for
biological activities.
• Role
• ATP functions as a carrier of energy, as all biological
activities which require energy are ATP dependent.
This energy is given to various cellular processes in
chemical form.

9. • ATP ------→ ADP + Pi + Energy (7.3 K cal)
• ATP transports chemical energy within cells for
metabolism
• ATP is used by enzymes and structural proteins in many
cellular processes, including biosynthetic reactions,
motility, and cell division
• ATP is used as a substrate in signal transduction.
• Phosphorylation of ADP to ATP require energy & take
place in mitochondria hence iis called Power house of
cell.
• ATP ------→ ADP + Pi + Energy (7.3 Kcal)
• Mitochondria mostly
• ADP + Pi + Energy (7.3 Kcal) ------→ ATP

10. • Major pathway of Carbohydrate Metabolism:-
1) Glycolysis— It involve sequential reaction which
convert glucose into pyruvate / Lactate.
2) Krebs cycle— It involve oxidation of acetyl CoA to
CO2. It is last common pathway for carbohydrate,
Fats/ amino acids, through acetyl CoA.
3) Glycogenesis: It is the process of conversion of
glucose into glycogen in the liver.
4) Glycogenolysis: The breakdown of glycogen into
glucose is called as glycogenolysis.
5) Gluconeogenesis: It is the process of synthesis of
glucose from non-carbohydrate sources such as
amino acids, lactic acid and glycerol, etc.

11. 6) Pentose Phosphate pathway (HMP shunt): It
is alternative pathway for glycolysis & kreb
cycle for oxidation of glucose.
7) Uronic acid pathway: It is also alternative
pathway for oxidation of glucose, in which
glucose is converted into glucuronic acid,
pentoses.

12. • Explain pathway of glycolysis in detail.
• Glycolysis is also known as Embden – Meyerhof
pathway (EM pathway).
• Glycolysis take place in presence of oxygen i.e.
aerobic condition/ in absence of oxygen i.e.
anaerobic condition.
• Pyruvic acid is end product in aerobic condition
• Lactic acid is end product in anaerobic condition,
energy obtained is anaerobically hence process is
called anaerobic fermentation.
• Overall reaction— Anaerobic
• C6H12O6 + 2ADP + 2Pi -----→ 2 lactic acid + 2 ATP +
2H2O

13. • Aerobic
Glucose + 2NAD+ + 2 ADP + 2 Pi → 2 Pyruvate + 2 ATP + 2
NADH + 2 H2O
• Reaction involved in glycolysis:
It’s a main pathway for glucose oxidation
1. Phosphorylation of glucose to glucose 6 phosphate in
presence of enzyme hexokinase & ATP & Mg
2. Isomerisation of Glucose-6-phosphate to
fructose-6-phosphate in presence of Phosphohexose
isomerase
3. Phosphorylation of fructose-6-phosphate to
fructose-1,6-diphosphate in presence of
phosphofructokinase, ATP & Mg.
4. Cleavage of fructose-1,6-diphosphate to dihydroxy-
acetone phosphate & Glyceraldehyde-3-phosphate in
presence of aldolase.
These 2 products are interconvertible in presence of
triose phosphate isomerase

14. 5. Glyceraldehyde-3-phosphate further undergoes
oxidation to 1,3-diphosphoglycerate in presence of
glyceraldehyde-3-phosphate dehydrogenase &
NAD+
6. Transformation of 1,3-diphosphoglycerate to 3-
phosphoglycerate in presence of phosphoglycerate
kinase, Mg & ADP. PO4 from
1,3-diphosphoglycerate is transferred to ADP
forming ATP.
7. 3- phosphoglycerate changes to
2-phosphoglycerate in presence of
phosphoglycerate mutase
8. Loss of water molecule from 2-phosphoglycerate
results into formation of phosphoenol pyruvic acid
in presence of enolase

15. 9. Loss of phosphate from phosphoenol pyruvic acid
results into formation of Enol pyruvic acid in
presence of pyruvate kinase, Mg & ADP. PO4 from
phosphoenol pyruvic acid is transferred to ADP
forming ATP.
11.pyruvic acid under aerobic conditions enter TCA
cycle in mitochondria.
Pyruvic acid forms main end product of glycolysis
in those tissues which are supplied with sufficient
Oxygen
12. But tissues where oxygen is not supplied, lactic
acid is formed as an end product of glycolysis by
reduction in presence of lactate dehydrogenase &
NADH

16. 1
2
6
4
3
7
isomerase 5
(2)
(2)

17. 11
10
9
8
(2)
(2)
(2)
(2) Aerobic
Anaerobic

20. • Energetic of glycolysis—
• Total ATP formed in aerobic condition-
• Reaction ATP formed
1) Glyceraldehyde-3-PO4 → 6
1,3-diphosphoglycerate
2) 1,3-diphosphoglycerate → 2
3-phosphoglycerate
3) Phosphoenol pyruvate → 2
Pyruvate
Total= 10

21. • ATP consumed in
• Reaction ATP Consumed
1) Glucose → 1
G-6-PO4
2) Fructose-6-phosphate → 1
F-1,6-di PO4
Total = 2
❑ Net ATP synthesized in Aerobic glycolysis = 8.

22. • Total ATP formed in anaerobic condition-
• Reaction ATP formed
1) Glyceraldehyde-3-PO4 → 1,3-diphosphoglycerate 6
2) 1,3-diphosphoglycerate → 3-phosphoglycerate 2
3) Phosphoenol pyruvate → Pyruvate 2
Total = 10
• ATP consumed in
• Reaction ATP
Consumed
1) Glucose → G-6-PO4 1
2) Fructose-6-phosphate → F-1,6-di PO4 1
3) Pyruvate → Lactate 6
Total = 8
❑ Net ATP synthesized in anaerobic glycolysis = 2

23. TCA Cycle
Mitochondria

25. • Kreb’s cycle/ Citric acid cycle/ Tricarboxylic acid
cylcle: (C3 cycle/ TCA)
• It’s a central pathway for release of energy from acetyl
CoA which is produced from glycolysis, catabolism of
fatty acids or amino acids.
• The cycle mostly occurs in mitochondria because
enzyme required for reaction are present in
mitochondrial matrix.
1. Condensation of acetyl CoA obtained from pyruvic
acid with oxaloacetate to form citric acid in presence
of citrate synthase
2. Conversion of citric acid to cis aconitate in presence of
aconitase & Fe2+
3. Cis acotinic acid accepts water to give isocitric acid in
presence of acotinase & Fe2

26. 4. Isocitric acid undergoes oxidation in presence of isocitric
dehydrogenase & NAD+ to give Oxalosuccinic acid
5. Decarboxylation of oxalosuccinic acid to alpha ketoglutaric
acid in presence of isocitrate dehydrogenase, Mg/ Mn
6. Oxidative decarboxylation of alpha ketoglutaric acid to
succinyl CoA in presence of alpha ketoglutarate
dehydrogenase, CoA-SH, NAD+, Mg
7. Succinyl Coa gets converted to succinic acid in presence of
succinate thiokinase, GDP, Mg
8. Succinic acid undergoes dehydrogenation in presence of
succinate dehydrogenase, FAD+ to form fumaric acid
9. Fumaric acid takes up water molecule in presence of
fumarase to form maleic acid
10. Maleic acid undergoes oxidation in presence of malate
dehydrogenase, NAD+ to form oxaloacetic acid.
11. Cycle gets repeated again by entrance of another molecule
of Acetyl CoA

27. • Energetic of TCA cycle:
• Reation ATP molecule formed
1) Isocitrate→ Oxalosuccinate 3
2) α Ketoglutarate→ succinyl CoA 3
3) Succinyl CoA→ succinate 1
4) Succinate→ fumarate 2
5) Malate →oxaloacetate 3
Total - 12
• As one molecule of glucose give 2 molecule of
pyruvate so total no. of ATP formed in TCA cycle =
12 X 2 = 24

28. • Total ATP formed in aerobic oxidation
Cycle ATP formed
1) From TCA cycle = 24
2) From glycolysis = 8
3) From 2 Pyruvate → 2 Acetyl CoA= 6
Total= 38
• Total CO2 formed= 3 molecule
• Total H2O formed = 2 molecule.

30. • What is the importance of electron transport & oxidative
phosphorylation in carbohydrate metabolism?
• Most of the free energy released during the oxidation of
glucose to CO2
is retained in the reduced co-enzymes NADH
and FADH2
generated during glycolysis and the citric acid
cycle.
• During respiration, electrons are released from NADH and
FADH2
and eventually are transferred to O2
, forming H2
O
according to the following overall reactions:
• NADH + H+
+ ½ O2
= NAD+
+ H2
O
• FADH2
+ ½ O2
= FAD + H2
O
• Importance :
1. To transfer electrons from NADH and FADH2
to the oxygen so
as to form water.
2 .These electrons are used to power ATP production.

31. • The conc. of glucose is maintained constant in blood
i.e. 80-100 mg which is regulated by hormonal
mechanism irrespective of dietary carbohydrate
content.
• Hormones like insulin & glucagon regulate blood
glucose level. It is called as homeostasis of blood
glucose. Both the hormone are present in pancreas.
• Insulin= it reduces glucose level by synthesizing
glycogen & reduce gluconeogenesis.
• If pancreas fails to produce sufficient insulin/
produce ineffective form of insulin →blood glucose
increases → Diabetes mellitus .
• During this glucose is seen in urine.

32. • Hyperglycemia= It is rise in blood glucose level →
due to DM / malfunctioning of liver.
• Hypoglycemia= Blood sugar level is low →Due to
starvation →Due to excess intake of drugs

33. • Define & explain Glycogenesis. Give importance of the process.
• Definition Of Glycogenesis:
• It is the process of conversion of glucose into glycogen in the liver. It
takes place in the cytosol , requires ATP and UTP, besides glucose.
• Importance of glycogenesis:
1. Excess of glucose is utilised to form glycogen which is stored in liver
and muscles reserved for muscular activities.
2. Helps to maintain blood glucose level.
3. In case of carbohydrate starvation stored glycogen is converted to
glucose to give energy.
• Explanation: Diagrammatic presentation can also be considered
• 1. Synthesis on UDP – Glucose
• 2. Requirement of primer to initiate glycogenesis.
• 3. Glycogen synthesis by Glycogen synthase.
• 4. Formation of branches in glycogen.

35. • Abnormal Metabolism –
1. Diabetes mellitus: It is metabolic disorder in
which body is unable to utilize glucose.
• It is of two types— i) Insulin dependent DM
ii) Non-insulin dependent DM.
• It is characterized by following symptoms
1) Hyperglycemia 2) Polyphagia
3) Glycosuria 4) Polyuria
5) Polydipsia 6) Ketosis
7) Marked loss of weight 8)Light color of urine.

36. • Treatment:
i) DM can be treated by anti-diabetic drugs. Or by
administering insulin SC.
II) Patient is advised to take high protein diet and low
carbohydrate diet and exercise.
2. Pentosuria— pentose sugar is less utilized & are
seen in urine.
3. Galactosemia— due to deficiency of enzyme
galactose-1-phosphate uridyltransferase
galactokinase, galactose cannot be converted into
glucose, which lead to galactosemia.
4. Fructosemia—defective metabolism of fructose
develop high conc. of fructose in blood is called as
fructosemia.etc

37. • Co-enzyme Name
1) Vitamin B1= TPP
--(Thiamine pyrophosphate) = 1 ATP
2) Vitamin B3= NAD
—( nicotinamide adenine dinucleotide) &
NADP--( nicotinamide adenine dinucleotide
phosphate )
3)Vit B2= Riboflavin
FMN-- (Flavin mononucleotide ) and
FAD-- (Flavin adenine dinucleotide)
4) GTT– Guanine Tri- Phosphate= 1 ATP
2
ATP
3 ATP

38. • Dietary protein provide fixed amt of nitrogen
proteins are hydrolyzed to amino acids & are
absorbed in GIT.
• A series of proteolytic enzymes are involved in
hydrolysis of proteins to amino acids.
Protein Metabolism

41. • Catabolism of amino group of amino acid:
1) Deamination—
• This is 1st
step in metabolic breakdown of amino
acid.
• It involve removal α-amino group of amino acid
to α-keto acid in presence of oxidase enzyme.
• The chief site of deamination is in liver.

42. • At physiological pH the 99% NH3 is in the ionic
form.
• NH3 is toxic & it is used for synthesis of urea to
reduce toxicity.
• Elimination of –NH2 functional group as NH3 by
oxidase enzyme is called as oxidative deamination.

43. 2) transamination in protein catabolism.
• In transamination, the NH2 group on one molecule
is exchanged with the C =O group on the other
molecule.
• The amino acid becomes α-keto acid, and
the α-keto acid becomes an amino acid.
• In this example α-ketoglutaric acid becomes
glutamic acid, amino acid becomes α-keto acid.
• This reaction is reversible.
• It is important for redistribution of amino group and
production of non-essential amino acid as per the
requirement of the cell.

45. 3) Oxidative deamination:
• An amino acid is converted into the
corresponding α-keto acid by the removal of the
amine functional group as ammonia and the amine
functional group is replaced by the ketone group.
• The ammonia eventually goes into the urea cycle.
• The main sites for this reaction are liver and
kidney.
• The reaction is catalysed by amino acid oxidase
enzymes.
• Reaction:

47. ❑ Describe biosynthetic pathway of urea in
body.
• Excess of nitrogen resulting from aa catabolism is
excreted in the form of urea.
• Urea thrown out of the body through urine.
• Urea cycle occurs mainly in liver, but also in & kidney.
1)Molecule of ammonia, CO2 & phosphate are
condensed to form ‘Carbamoyl phosphate’ in presence
of enzyme ‘carbamoyl-phosphate synthetase.
2) Carbamoyl phosphate transferred to ornithine forms
citrulline in presence of an enzyme ornithine
transcarbamoylase.
• This reaction takes place in mitochondria.
• The citruline formed in this reaction enters in
cytoplasm & the next reactions take place in cytoplasm

48. 3) Citrulline condenses with Aspartate to form
argininosuccinate. The reaction is catalysed by an
enzyme Arginosuccinate synthetase.
4) Arginosuccinate is now cleaved into ‘arginine’ &
‘fumarate’ by the enzyme ‘arginosuccinase’.
Fumarate formed may be converted to oxaloacetate
via the actions of enzymes ‘fumerase’& malate
dehydrogenase & then transmitted to regenerate
aspartate.
5) Finally arginine is cleaved into ornithine & urea by
the enzyme arginase.
• With this reaction cycle is completed & ornithine
molecule accepts molecule of carbamoyl phosphate
to repeat the cycle.
• The overall equation of the urea cycle is:
NH3 + CO2 + aspartate + 3 ATP + 2 H2O → urea +
fumarate + 2 ADP + 4 Pi + AMP.

52. • Abnormal Metabolism Of Protein: (Inborn Error)
1) Phenylketonuria (Phenylketonuria):
• Genetic disorder related to phenylalanine
metabolism.
• Phenylalanine is precursor for biosynthesis of
Tyrosine.
• In catabolism of phenylalanine, 1st
enzyme
phenylalanine hydroxylase convert
phenylalanine------🡪 Tyrosine.
• The inherited deficiency of this enzyme result in
accumulation of phenylalanine, & is excreted as
phenyl pyruvate.
• This condition is called Phenylketonuria.

53. • It affect young children associated with severe
mental retardation.
•

54. • Write in short about Alkaptonuria.
• Alkaptonuria:
• This is a metabolic disorder of phenylalanine due to
lack of enzyme homogentisate deoxygenase
resulting into accumulation of homogentisate,
which is excreted via urine.
• Homogentisate gets oxidized to corresponding
quinone which polymerizes to give black or brown
pigment ‘alkaptone’ & this colours urine.
• In cartilage and connective tissues, homogentisate
gets polymerized and results into arthritis.

56. 3) Hyper-ammonemia:
• Deficiency of urea cycle enzymes result into
accumulation of citrulline, argininosuccinate,
arginine in liver.
• It reduces formation of urea, due to this NH3 in
blood increases.
• Mostly it result into death, but it can be controlled
by feeding low nitrogen diet & 2-oxoacid part of
essential a.a which will reduce NH3 conc.
4) Hartnup’s Disease:
• It is metabolic disorder of tryptophan catabolism.

57. • Deficiency of Tryptophan pyrrolase result into
accumulation of tryptophan & its derivative
indoleacetic acid, indole pyruvic acid, etc.
5) Hypervalinemia:
• In it Valine transaminase enzyme deficiency results
in accumulation of valine in blood called
hypervalinemia.
6) Maple Syrup Urine disease:
• It is metabolic disorder branched amino acid.
• Deficiency of α-keto dehydrogenase result in
accumulation of branched α-keto acid & they are
excreted via. urine

58. Thank you