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Citric Acid Cycle

Renu Maurya

Citric Acid Cycle

CITRIC ACID CYCLE/KREBS CYCLE/TRICARBOXYLIC ACID (TCA Cycle)

  • The Citric acid cycle is the most important metabolic pathway for the energy supply to the body in which 65-70% of ATP is synthesized.
  • Citric acid cycle involves final common pathway of the oxidation of acetyl CoA to CO2 & H2O from carbohydrates, fatty acids and amino acids.
  • The site of occurance of TCA cycle enzymes is mitochondrial matrix except for succinate dehydrogenase found in inner mitochondrial membrane.
  • The cycle operates in aerobic conditions. 

Reactions of Critric acid cycle-

  • Step 1- The 4 carbon, oxaloacetate condenses with 2 carbon, acetyl CoA to form 6 carbon compound, a tricarboxylic acid by enzyme citrate synthase. (irreversible step) 
  • Step 2-  Citrate is isomerized to isocitrate by the enzyme aconitase. 
  • Step 3- The enzyme isocitrate dehydrogenase catalyses the conversion of isocitrate to oxalosuccinate and then to α-ketoglutarate. (irreversible step & NADH is formed) 
  • Step 4- Conversion of α-ketoglutarate to succinyl CoA catalyzed by α-ketoglutarate dehydrogenase. (NADH formed) 
  • Step 5- Succinyl CoA is converted to succinate by enzyme Succinate thiokinase. This is substrate level phosphorylation
  • GTP is converted to ATP by enzyme nucleoside diphosphate kinase. 
  • Step 6- Succinate is oxidized by succinate dehydrogenase to fumarate.(FADH2 formed) 
  • Step 7- Fumate is converted to malate by enzyme fumarase. 
  • Step 8- Malate is oxidised to oxaloacetate by malate dehydrogenase. (NADH formed) 

Inhibitors of Krebs Cycle-

Enzyme Inhibitor
Aconitase Fluoroacetate
α-ketoglutarate dehydrogenase Arsenite
Succinate dehydrogenase Malonate
  •  12 ATPs are produced from one acetyl CoA. 
  •  Krebs cycle is both catabolic and anabolic in nature so called amphibolic.
  • Anaplerotic reactions are “filling up” reactions or “influx” reactions or replenishing reactions which supply 4 carbon units to the TCA cycle. 
  • ATP, NADH, acetyl CoA & succinyl CoA acts as an allosteric inhibitor to citrate synthase.
  • ATP and NADH inhibit isocitrate dehydrogenase and activated by ADP. 
  • Alpha ketoglutarate dehydrogenase is inhibited by succinyl CoA and NADH. 
  • TCA cycle is involved in gluconeogenesis, transamination, deamination. 
  • Vitamins play a key role in TCA cycle-
  1. Riboflavin
  2. Niacin
  3. Thiamine
  4. Pantothenic acid  

Exam Important

  • There is no net generation oxaloacetate or cycle intermittents.
  • First product of the cycle is citrate.
  • Two irreversible steps are- 
    • oxaloacetate to citrate catalyzed by citrate (synthase)
    • alpha ketoglutarate to succinyl CoA.
  • NADH is produced and CO2 is liberated.
  • GTP is produced by substrate level phosphorylation by succinate thiokinase.
  • 4 dehydrogenases are used in Kreb’s cycle.
  • Isolucine, Methionine, Valine enter by conversion into succinyl CoA.
  • Tyrosine, phenylalanine enter conversion into fumarate.
  • Pyruvate Carboxylase reaction is the classical example of the anaplerotic reaction.
Don’t Forget to Solve all the previous Year Question asked on Citric Acid Cycle

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