Transcript Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle

Tricarboxylic acid cycle (TCA Cycle)
[Kreb’s cycle] [Citric acid cycle]
Is the final common oxidative pathway for
carbohydrates, fats and amino acids
Along with energy, cycle supplies many intermediates
required for the synthesis of amino acids, glucose,
heme etc
 Site: mitochondrial matrix
 Oxidation of acetyl CoA  Co2 + H2O
 Occurs in a cyclic manner, generate ATP
 Two carbon, acetyl CoA + 4 carbon, Oxaloacetate
= 6 carbon tricarboxylic acid, citrate
Cis-aconitate is a transient one with very short half-life.
Immediate H2O added to it and forms Isocitrate
CO2
 Isocitrate  oxalosuccinate -ketoglutatrate.
It is an oxidative decarboxylation
Oxalosuccinate is unstable so it undergoes spontaneous
decarboxylation to from  -KG
TCA is both catabolic and anabolic  amphibolic
Energetics of TCA Cycle
Steps 4, 6, 10  3 NADH
1 NADH = 3 ATP]
3 ATP x 3 = 9 ATP
Step 8  1 FADH2
1 FADH2 = 2 ATP]
2 ATP x 1 = 2 ATP
Step 7  1 GTP
1 GTP = 1 ATP
1 ATP x 1 = 1 ATP
Therefore 1 acetyl CoA gives
12 ATP
Therefore 1 acetyl CoA gives 12 ATP
Two acetyl CoA in citric acid cycle produces
24 ATP
Energetics of complete oxidation of glucose
Aerobic glycolysis 
8 ATP
Oxidation of 2 pyruvate =
6 ATP
Oxidation of 2 Acetyl CoA by TCA cycle 
24 ATP
Net Gain = 38 ATP
Amphibolic nature of TCA cycle
Non essential aa
Aspartate Acetyl CoA
Purines , Transamination
Pyrimidines.
Oxaloacetate
Citrate Acetyl CoA
Fatty acids,
steroids
Pyruvate
 -KG
Transanimation
Succinyl COA
Glutamate
Malate
Heme
Non-essential a a,
purines
Anaplerosis
The reactions concerned to replenish the intermediates of
TCA cycle are called anaplerotic reactions or anaplerosis
Pyruvate +CO2 + ATP carboxylase oxaloacetate + ADP + Pi
Pyruvate +CO2 + NADPH + H + Malic enzyme Malate
Inhibitors that inhibit the enzymes of TCA cycle are:
Aconitase
fluoroacetate
- Ketoglutarate DH
Arsenite
Non-competitive
Succinate DH
Malonate
}- competitive
Regulation of TCA cycle
1. Citrate synthase: inhibited by ATP, NADH, acyl CoA
and succinyl CoA
2. Isocitrate dehydrogenase: Inhibited by ATP and NADH
and activated by ADP
3. -KG dehydrogenase inhibited by NADH & succinyl CoA
The availability of ADP: Important for proceeding the TCA
cycle
if not oxidation of NADH and FADH2 through election transport
chain stops. Accumulation of NADH and FADH2, inhibit the
enzymes of TCA cycle.
Ref: Essentials of Biochemistry/Handbook of Biochemistry