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Tricarboxylic acid cycle (TCA Cycle) [Kreb’s cycle] [Citric acid cycle] PowerPoint Presentation
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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

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tricarboxylic acid cycle tca cycle kreb s cycle citric acid 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
  • Twocarbon, acetyl CoA + 4 carbon, Oxaloacetate

= 6 carbon tricarboxylic acid, citrate

slide3

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

slide4

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

slide5

Amphibolic nature of TCA cycle

Non essential aa Aspartate Acetyl CoA

Purines , Transamination

Pyrimidines.

Oxaloacetate Citrate Acetyl CoA

Fatty acids,

steroids

Pyruvate Malate  -KG

Transanimation

Succinyl COA Glutamate

Heme Non-essential a a,

purines

slide6

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

slide7

Regulation of TCA cycle

  • 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