These are major source of energy for living organisms.
Supplying a huge array of metabolic intermediates for biosynthetic reactions.
The structural elements in cell coat or connective tissues.
3. Biological significance of
Carbohydrates
â˘These are major source of energy for
living organisms.
â˘Supplying a huge array of metabolic
intermediates for biosynthetic
reactions.
â˘The structural elements in cell coat
or connective tissues.
4. Digestion :
⢠Partly digested in mouth by salivary
amylase.
⢠In stomach there is no digestion takes
place.
⢠Complete digestion and absorption
will be taken place at small intestine
12. â˘The anaerobic catabolic pathway by
which a molecule of glucose is
broken down into two molecules of
lactate.
Glucose â 2 Lactic acid (lack of O2)
â˘All of the enzymes of glycolysis
locate in cytosol.
15. â˘Phosphorylated Glucose cannot get
out from cell.
â˘Hexokinase (having 4 Isoenzymes).
â˘Glucokinase, GK in liver.
â˘Irreversible.
(1) Glucose is phosphorylated to
Glucose 6-phosphate
OH
OH
H
OH
H
OHH
OH
CH2
H
HO
OH
OH
H
OH
H
OHH
OH
CH2
H
OP
ATP ADP
Hexokinase
Mg2+
G G-6-P
16. Particulars Hexokinase Glucokinase
Occurrence in all tissues only in liver
Km value 0.1mmol/L 10mmol/L
Substrate Glucose,
Fructose,
Mannose
Glucose
Regulation G-6-P Insulin
Comparison of
Hexokinase and Glucokinase
17. (2) G-6-P is isomerised to Fructose 6-P
OH
OH
H
OH
H
OHH
OH
CH2
H
OP
G-6-P
isomerase OH
CH2OH
H
CH2
OH H
H OH
O
OP
F-6-P
18. (3) F-6-P is phosphorylated Fructose
1,6-bisphosphate
â˘The second phosphorylation
â˘Phosphofructokinase-1, PFK-1
OH
CH2OH
H
CH2
OH H
H OH
O
OP
F-1,6-BP
OH
CH2
H
CH2
OH H
H OH
O
OP O P
ATP ADP
Mg2+
F-6-P
PFK-1
19. (4) F-1,6-BP cleaved to 2 Triose
phosphates
â˘Reversible
F-1,6-BP
CH2
C O
C HHO
C OHH
C OHH
CH2
O P
O P
CH2
C O
O P CHO
CHOH
CH2 O PCH2OH
+
aldolase
dihydroxyacetone
phosphate,
DHAP
glyceraldehyde
3-phosphate,
GAP
20. (5) Triose phosphate isomerization
Gâ2 molecule glyceraldehyde-3-
phosphate, consume 2 ATP .
CH2
C O
O P CHO
CHOH
CH2 O PCH2OH
DHAP GAP
phosphotriose
isomerase
21. (6) Glyceraldehyde 3-phosphate oxidised
1,3-bisphospho glycerate
CHO
CHOH
CH2 O P
NAD+
NADH+H +
Pi
glyceraldehyde
3-phosphate
dehydrogenase,
GAPDH
C
CHOH
CH2 O P
O O~ P
glycerate
1,3-bisphosphate,
1,3-BPG
glyceraldehyde
3-phosphate
22. (7) 1,3-BPG dephosphorylated to 3-
phospho glycerate
⢠Substrate level phosphorylation
COO-
CHOH
CH2 O P
C
CHOH
CH2 O P
O O~ P
ADP ATP
glycerate
1,3-bisphosphate
glycerate
3-phosphate
Phosphoglycerate
kinase
23. (8) Glycerate 3-phosphate mutated
glycerate 2-phosphate
COO-
CHOH
CH2 O P
COO-
CH
CH2OH
O P
glycerate
3-phosphate
glycerate
2-phosphate
Mutase
24. (9) Glycerate 2-phosphate â
phosphoenol pyruvate
COO-
CH
CH2OH
O P
COO-
C
CH2
O
PEP
~ P + H2O
enolase
glycerate
2-phosphate
25. (10) PEP âpyruvate
⢠Second substrate level
phosphorylation
⢠irreversible
COO-
C
CH3
ADP ATP
COO-
C
CH2
O
PEP
~ P
pyruvate kinase
O
Pyruvate
27. Summary of Glycolysis
ATP
ADP
Mg2+
PFK-1
GAP DHAP
glycerate
1,3-bisphosphate
NADH+H+
glyceraldehyde
3-phosphate
dehydrogenase
H3PO4
NADH+H+
NAD+
ADP
ATP
glycerate
3-phosphate
glycerate
2-phosphate
H2O
PEP
ATP
ADP
pyruvate kinase
lactate
pyruvate
G G-6-P F- 6-P F- 1,6-BP
NAD+
Phosphoglycerate
kinase
Isomerase
Aldolase
Mutase
Enolase
LDH
HK
ATP
ADP
Mg2+
28. ďTotal reaction:
C6H12O6 + 2ADP + 2Pi
2CH3CHOHCOOH + 2ATP + 2H2O
ďFormation of ATP:
The net yield is 2 ~P or 2 molecules of
ATP per glucose.
29. 2. Regulation of Glycolysis
⢠Three key enzymes catalyze
irreversible reactions : Hexokinase,
Phosphofructokinase & Pyruvate
Kinase.
30. 1) PFK-1
The reaction catalyzed by PFK-1 is
usually the rate-limiting step of the
Glycolysis pathway.
This enzyme is regulated by covalent
modification, allosteric regulation.
32. 2) Pyruvate kinase
⢠Allosteric regulation:
F-1,6-BP acts as allosteric activator ďź
ATP and Ala in liver act as allosteric
inhibitors;
33. ⢠Covalent modification:
phosphorylated by Glucagon
through cAMP and PKA and inhibited.
ATP ADP
PKA
Glucagon
Pyruvate Kinase
(active)
Pyruvate Kinase- P
(inactive)
cAMP
34. 3) Hexokinase and glucokinase
⢠This enzyme is regulated by covalent
modification, allosteric regulation and
isoenzyme regulation.
⢠Inhibited by its product G-6-P.
⢠Insulin induces synthesis of
glucokinase.
35. 3. Significance of glycolysis
1) Glycolysis is the emergency energy-
yielding pathway.
2) Glycolysis is the main way to
produce ATP in some tissues, even
though the oxygen supply is
sufficient, such as red blood cells,
retina, testis, skin, medulla of kidney.
⢠In glycolysis, 1mol G produces 2mol
lactic acid and 2mol ATP.
37. ⢠The process of complete
oxidation of glucose to CO2 and
water with liberation of energy as
the form of ATP is named aerobic
oxidation.
⢠The main pathway of G oxidation.
38. 1. Process of aerobic oxidation
G Pyr
cytosol Mitochodria
glycolytic
pathway
second
stage
third
stage
CO2 + H2O+ATPPyr CH3CO~SCoA
first
stage
TAC
39. 1) Oxidative decarboxylation of
Pyruvate to Acetyl CoA
⢠irreversible;
⢠in mitochodria.
COO-
C
CH3
NAD+
NADH + H +
O
pyruvate
CH3C
Pyruvate
dehydrogenase
complex
Acetyl CoA
O
~SCoA+ HSCoA + CO2
43. S S
CH
H2
C
H2C (CH2)4 COOH
SH SH
CH
H2
C
H2C (CH2)4 COOH
+2H
- 2H
lipoic acid dihydrolipoic acid
C
C
NH2
HC
N
C
H2
S
C
C
N
C
N
C
H
CH3
CH2CH2H3C O P O
O-
O
P
O
O-
O-
+
TPP
44. HSCoA
HS CH2 CH2 NH C CH2
O
CH2 NH C C
O
OH
H
C CH2
CH3
CH3
O P O
OH
O
P
OH
O
O
3'AMP
ÂŚĂ-alanine pantoic acid pyrophosphate
pantothenic acid
4'-phosphopantotheine
ÂŚĂ-mercapto-
ethylamine
46. 2) Tricarboxylic acid cycle, TCAC
⢠The cycle comprises the combination of a
molecule of acetyl-CoA with oxaloacetate,
resulting in the formation of a six-carbon
tricarboxylic acid, citrate. There follows a
series of reactions in the course of which
two molecules of CO2 are released and
oxaloacetate is regenerated.
⢠Also called citrate cycle or Krebs cycle.
53. ⥠The net reaction of the TCAC:
acetylCoA+3NAD+
+FAD+GDP+Pi+2H2O
â2CO2+3NADH+3H+
+FADH2+GTP+
HSCoA
⢠Irreversible and aerobic reaction
⣠The enzymes are located in the
mitochondrial matrix.
54. ⤠Anaplerotic reaction of
oxaloacetate
pyruvate carboxylase
Biotin
ATP ADP + Pi
+ CO2C
CH3
COOH
O
C
C
COOH
COOH
O
H2
NAD+
NADH+H+
malic acid DH
+ CO2
malic enzyme
C
CH3
COOH
O
NADPH+H+
NADP+
CHOH
C
COOH
COOH
C
C
COOH
COOH
O
H2H2
55. (2) Bio-significance of TCAC
â Acts as the final common pathway for
the oxidation of carbohydrates, lipids,
and proteins.
⥠Serves as the crossroad for the
interconversion among carbohydrates,
lipids, and non-essential amino acids,
and as a source of biosynthetic
intermediates.
57. 2. ATP produced in the aerobic
oxidation
⢠acetyl CoA â TCAC : 3 (NADH+H+
) +
FADH2 + 1GTP â 12 ATP.
⢠pyruvate âacetyl CoA: NADH+H+
â3 ATP
⢠1 G â 2 pyruvate : 2(NADH+H+
) â 6 or
8ATP
1mol G ďź 36 or 38mol ATP
ďź 12 ďź 3 ďź Ă2 ďź 6 ďź 8 ďźďź
36 ďź 38 ďź
58. 3. The regulation of aerobic
oxidation
⢠The Key Enzymes of aerobic oxidation
The Key Enzymes of glycolysis
Pyruvate Dehydrogenase Complex
Citrate synthase
Isocitrate dehydrogenase (rate-limiting )
Îą-Ketoglutarate dehydrogenase
63. 4. Pasteur Effect
⢠Under aerobic conditions, glycolysis is
inhibited and this inhibitory effect of
oxygen on glycolysis is known as
Pasteur effect.
⢠The key point is NADH ďź
NADH mitochondria
Pyr TCAC CO2 ďź H2O
Pyr canât produce to lactate.
68. The net reation:
3G-6-P + 6NADP+
â
2F-6-P + GAP + 6NADPH + H+
+ 3CO2
2. Regulation of pentose phosphate
pathway
ďˇ Glucose-6-phosphate Dehydrogenase is the
rate-limiting enzyme.
NADPH/NADP+
â, inhibit;
NADPH/NADP+
â, activate.
69. 3. Significance of pentose
Phosphate pathway
1) To supply ribose 5-phosphate for bio-
synthesis of nucleic acid;
2) To supply NADPH as H-donor in
metabolism;
ďŽ NADPH is very important âreducing
powerâ for the synthesis of fatty acids
and cholesterol, and amino acids, etc.
70. ďŽ NADPH is the coenzyme of glutathione
reductase to keep the normal level of
reduced glutathione;
So, NADPH, glutathione and glutathione
reductase together will preserved the integrity
of RBC membrane.
2GSH
G-S-S-G NADPH + H+
glutathione reductase
NADP+H2O2
2H2O
71. Deficiency of glucose 6-phosphate
dehydrogenase results in hemolytic
anemia.
favism
ďŽ NADPH serves as the coenzyme of
mixed function oxidases (mono-
oxygenases). In liver this enzyme
participates in biotransformation.
73. Glycogen is a polymer of glucose
residues linked by
ďˇ Îą (1â4) glycosidic bonds, mainly
ďˇ Îą (1â6) glycosidic bonds, at
branch points.
74.
75. ⢠The process of glycogenesis
occurs in cytosol of liver and
skeletal muscle mainly.
1. Glycogen synthesis (Glycogenesis)
76. ⢠UDPG: G active pattern, G active donor.
⢠In glycogen anabolism, 1 G consumes
2~P.
⢠Glycogen synthase: key E.
G
HK or GK
G-6-P
ATP ADP
G-1-P
UDPG
pyrophosphorylase
UDPG
UTP PPi Gn UDP
Gn+1
glycogen
synthase
80. Phosphorylase: key E;
The end products: 85% of G-1-P and 15%
of free G;
There is no the activity of glucose 6-
phosphatase (G-6-Pase) in skeletal
muscle.
Gn
Pi Gn-1
G-1-P G-6-P
G-6-Pase
H2O Pi
G
Phosphorylase
2. Glycogen catabolism (glycogenolysis)
83. 3. Regulation of glycogenesis and
glycogenolysis
1) Allosteric regulation
In liver:
G phosphorylase
glycogenolysis
In muscle:AMP phosphorylase-b
ATP
G-6-P
phosphorylase-a
glycogenolysis
Ca2+
85. glucagon, epinephrine
inactive
adenylate cyclase
active
adenylate cyclase
ATP cAMP
inactive
PKA
active
PKA
phosphorylase b
kinase
phosphorylase b
kinase
P
ATP
ADP
H2O
Pi
phosphorylase b
P
P
ATP ADP
Pi
H2O
ATP ADP
glycogen
synthase
glycogen
synthase
P
H2OPi
protein
phosphatase-1
(active) (inactive)
inhibitor-1
(active)
inhibitor-1
(inactive)
phosphorylase a
ATP
87. ⢠Concept:
The process of transformation of non-
carbohydrates to glucose or glycogen
is termed as gluconeogenesis.
⢠Materials: lactate, glycerol, pyruvate
and glucogenic amino acid.
⢠Site: mainly liver, kidney.
88. 1. Gluconeogenic pathway
⢠The main pathway for gluconeogenesis
is essentially a reversal of glycolysis,
but there are three energy barriers
obstructing a simple reversal of
glycolysis.
89. 1) The shunt of carboxylation of Pyr
PEP
ADP
ATP
oxaloacetic acid
Pyr carboxylase
ADP+Pi ATP CO2
Biotin
GTP
GDP
CO2
PEP carboxykinase
Pyr kinase
COO
-
C
CH3
COO
-
CH
CH2
O~ P
O
pyruvate
COO
-
C
CH2
O
COOH £¨ Mt.£Š
£¨ 1/3Mt. 2/3cytosal£Š.
90. 2) F-1, 6-BP âF-6-P
F-6-P F-1,6-BP
ATP ADP
Pi H2O
PFK-1
Fructose-
bisphosphatase
91. 3) G-6-P âG
⢠2 lactic acid G consume
ATP?
G G-6-P
ATP ADP
Pi H2O
Glucose-6-
phosphatase
HK
93. 2. Regulation of gluconeogenesis
⢠Substrate cycle:
The interconversion of two substrates
catalyzed by different enzymes for
singly direction reactions is called
âsubstrate cycleâ.
⢠The substrate cycle produces net
hydrolysis of ATP or GTP.------futile
cycle
94. Key enzymes of gluconeogenesis
PEP carboxykinase
Pyr carboxylase
Fructose-bisphosphatase
Glucose-6-phosphatase
97. 3. Significance of gluconeogenesis
(1) Replenishment of Glucose by
Gluconeogenesis and Maintaining
Normal Blood Sugar Level.
(2) Replenishment of Liver Glycogen.
(3) Regulation of Acid-base Balance.
99. Lactic acid (Cori) cycle
⢠Lactate, formed by the oxidation of
glucose in skeletal muscle and by
blood, is transported to the liver where
it re-forms glucose, which again
becomes available via the circulation
for oxidation in the tissues. This
process is known as the lactic acid
cycle or Cori cycle.
⢠prevent acidosis ďź reused lactate
102. 1. The source and fate of blood sugar
blood sugar
3.89ÂĄÂŤ 6.11mmol/L
dietary supply
liver glycogen
(gluconeogenesis)
other saccharides
CO2 + H2O + energy
glycogen
other saccharides
non-carbohydrates
>8.89ÂĄÂŤ10.00mmol/L
(threshold of kidney)
non-carbohydrate
(lipids and some
amino acids)
urine glucose
origin (income) fate (outcome)
103. Blood sugar level must be maintained
within a limited range to ensure the
supply of glucose to brain.
The blood glucose concentration is 3.89
ď˝ 6.11mmol/L normally.
104. 2. Regulation of blood sugar level
1 ďź insulin ďź for decreasing blood sugar
levels.
2 ďź glucagon ďź for increasing blood sugar
levels.
3 ďź glucocorticoid: for increasing blood
sugar levels.
4 ďź adrenaline ďź for increasing blood
sugar levels.