CITRIC ACID CYCLE

1
Citric Acid Cycle
R.C. Gupta Professor and Head Dept. of
Biochemistry National Institute of Medical
Sciences Jaipur, India
2
E M B - R C G
3
E M B - R C G
Hans A. Krebs
4
E M B - R C G
EMB-RCG
5
E M B - R C G
EMB-RCG
6
The cycle begins ...
With the condensation of
Acetyl CoA, a two-carbon compound
with
Oxaloacetate, a four-carbon compound
to form
Citrate, a six-carbon compound
7
By a series of reactions
8
Acetyl CoA
(2-carbon)
CoA
Citrate
Oxaloacetate
(6-carbon)
(4-carbon)
CO2
CO2
9
Sources of oxaloacetate
E M B - R C G
10

• But to increase the overall rate of
  CAC reactions, the concentration of intermediates
  has to be raised
• Reactions which lead to net entry of
  intermediates into the cycle are known as
  anaplerotic reactions

E M B - R C G
11
(No Transcript)
12
Pyruvate carboxylase is an allosteric enzyme it
is activated by acetyl CoA
13
Oxaloacetate is also formed by a trans- amination
reaction between aspartate and a-ketoglutarate
E M B - R C G
14
However, the transamination reaction is not
anaplerotic One intermediate of citric acid
cycle, oxaloacetate, is formed at the expense
of another, a-ketoglutarate
E M B - R C G
15
Sources of acetyl CoA
E M B - R C G
EMB-RCG
16
E M B - R C G
17
E M B - R C G
18
Oxidative decarboxylation of pyruvate
E M B - R C G
19
E M B - R C G
20
E M B - R C G
EMB-RCG
21
(No Transcript)
22
E M B - R C G
Note Lipoic acid is bonded to a lysine residue
of dihydrolipoyl acetyl transferase
EMB-RCG
23
The net reaction catalysed by pyruvate
dehydrogenase complex
24
Fate of acetyl CoA
E M B - R C G
EMB-RCG
25
EMB-RCG
26
Reactions of citric acid cycle
E M B - R C G
27
E M B - R C G
EMB-RCG
28
(No Transcript)
29
EMB-RCG
30
(No Transcript)
31
EMB-RCG
32
(No Transcript)
33
EMB-RCG
34
EMB-RCG
35
(No Transcript)
36
EMB-RCG
37
E M B - R C G
38
EMB-RCG
39
(No Transcript)
40
E M B - R C G
41
E M B - R C G
42
E M B - R C G
43
E M B - R C G
44
E M B - R C G
45
E M B - R C G
46
CH2 COOH

CH2 COOH
Succinate
FAD
E M B - R C G
Succinate
dehydrogenase
FADH2
H C COOH

HOOC C H
Fumarate
47
In the ninth reaction, fumarate is hydrated
to L-malate by fumarase
H C COOH

E M B - R C G
HOOC C H
Fumarate
H2O
Fumarase
HO CH COOH

CH2 COOH
L-Malate
48
E M B - R C G
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
E M B - R C G
53
E M B - R C G
54
Change in coenzyme
Energy captured
Reaction
Isocitrate to oxaloacetate
3 ATP equivalents
NAD NADH
a-Ketoglutarate to succinyl CoA
3 ATP equivalents
NAD NADH
Malate to oxaloacetate
NAD NADH
3 ATP equivalents
Succinate to fumarate
2 ATP equivalents
FAD FADH2
1 ATP equivalent
GDP GTP
12 ATP equivalents
Net gain
55
Energetics of oxidation of glucose
E M B - R C G
56
E M B - R C G
57
Efficiency of oxidation
E M B - R C G
58
E M B - R C G
59
E M B - R C G

60
Catabolic function
E M B - R C G
61
E M B - R C G
62
Glycerol is also released from lipids
This can be converted into pyruvate in the
glycolytic pathway
E M B - R C G
63
E M B - R C G
64
E M B - R C G
65
E M B - R C G
66
Anabolic function

• Glucose, fatty acids and many amino acids can be
  synthesized from inter-mediates of citric acid
  cycle
• Therefore, this cycle plays an important role in
  interconversion of nutrients

E M B - R C G
67
E M B - R C G
68
E M B - R C G
69
E M B - R C G
70
E M B - R C G
71
(No Transcript)
72
(No Transcript)
73
Gly, Ala, Ser, Thr, Cys, Trp, Hyp
Glycerol
Pyruvate
Glucose
Acetyl CoA
Fatty acids (C)
2n
Oxaloacetate
Asn Asp
Malate
Acetyl CoA
Citrate
Amphibolic role of CAC
Phe, Tyr
Fumarate
cis
-Aconitate
6
Isocitrate
Succinate
Succinyl CoA
Oxalosuccinate
Val
Met
Ile
a
-Ketoglutarate
Propionyl CoA
Glutamate
5
Fatty acids (C)
Pro
Gln
Arg
His
2n1
74
Capture of energy
E M B - R C G
75
Regulation
The major function of citric acid cycle is to
capture energy Availability of energy in the
cell is the major regulator of the pathway In
addition, some enzymes are allosteric enzymes
E M B - R C G
76
(No Transcript)
77
The allosteric inhibitors are
Enzyme Inhibitor
Citrate synthetase ATP and acyl CoA
Isocitrate dehydrogenase ATP and NADH
a-Ketoglutarate dehydrogenase NADH and succinyl CoA
E M B - R C G
78
(No Transcript)
79
Regulation in brain
E M B - R C G
80
E M B - R C G
81
E M B - R C G
82
E M B - R C G
83
E M B - R C G
84
E M B - R C G
85
EMB-RCG
86
E M B - R C G
87
E M B - R C G
88
(No Transcript)
89
E M B - R C G
90
Thank you