The Krebs cycle, also known as the citric acid cycle or TCA cycle, is the final common pathway that generates energy in the form of ATP, NADH, and FADH2 from the oxidation of pyruvate from glycolysis. Pyruvate enters the mitochondria and is converted to acetyl-CoA which condenses with oxaloacetate to form citrate, initiating the Krebs cycle. As the cycle progresses through 10 steps, high-energy electron carriers and GTP are produced to generate ATP through oxidative phosphorylation. The cycle regenerates oxaloacetate to continue multiple turns, completely oxidizing acetyl-CoA molecules for maximum energy production.

1. KREB’S CYCLE
Rajdip Majumder
Tutor,
Institute of Nursing,
Brainware University

2. Introduction
• Also known as citric acid cycle or TCA cycle(Tri
carboxylic acid) cycle.
• The pyruvate molecules released during glycolysis are
transported across the mitochondrial membrane into the
inner mitochondrial matrix , where they metabolized by
the enzymes called the Krebs cycle.
• During the cycle high energy molecules are created like
ATP, NADH and FADH2.
• The purpose is to generate more ATP.

3. Introduction
The primary function of TCA cycle is to provide more energy
in the form of ATP.
It is a final and common pathway for oxidation of
carbohydrate, lipid and protein via acetyl CoA.
The three carbon pyruvate molecules generated during
glycolysis moves from the cytoplasm into the mitochondrial
matrix, where it is converted by the enzyme pyruvate
dehydrogenase into a two carbon acetyl coA molecules. This is
the decarboxylation reaction. So the acetyl coA enters the
krebs cycle by combining with a four carbon molecule,
oxaloacetate, to form the six- carbon molecule citrate or citric
acid.

5. Reactions of TCA cycle
Step:1 Formation of citrate
• Oxaloacetate condenses with acetyl
CoA to form Citrate, catalysed by the
enzyme citrate synthase.
Steps 2 & 3 Citrate is isomerized to
isocitrate
• Citrate is isomerized to isocitrate by
the enzyme aconitase
Steps 4 & 5 Formation of α-
ketoglutarate
• Isocitrate dehydrogenase (ICDH)
catalyses the conversion of (oxidative
decarboxylation) of isocitrate to α -
ketoglutarate.
• The formation of NADH & the
liberation of CO2 occur at this stage.

6. Step: 6 Conversion of α -
ketoglutarate to succinyl CoA
• Occurs through oxidative
decarboxylation, catalysed by α -
ketoglutarate dehydrogenase
complex.
• At this stage of TCA cycle, second
NADH is produced & the second
CO2 is liberated.
Step: 7 Formation of succinate
• Succinyl CoA is converted to
succinate by succinyl- CoA
synthetase (Succinate thiokinase).
• This reaction is coupled with the
phosphorylation of GDP to GTP.
• GTP is converted to ATP by the
enzyme nucleoside diphosphate
kinase.

7. Step: 8 Conversion of succinate to
fumarate
• Succinate is oxidized by succinate
dehydrogenase to fumarate.
• This reaction results in the production
of FADH2.
Step: 9 Formation of malate: The
enzyme
Fumarase catalyses the conversion of
fumarate to malate.
Step:10 Conversion of malate to
oxaloacetate
• Malate is then oxidized to oxaloacetate
by malate dehydrogenase.
• The third & final synthesis of NADH
occurs at this stage.
• The oxaloacetate is regenerated which
can combine with another molecule of
acetyl CoA & continue the cycle.

9. Significance of TCA cycle:
Complete oxidation of acetyl CoA.
ATP generation.
Final common oxidative pathway.
For each turn of the cycle, three NADH, one ATP(
through GTP) and one FADH2 are created.
Excess carbohydrates are converted as neutral fat.