Citric acid cycle or TCA (tricarboxylic acid) cycle

1. Introduction

• Proposed by Hans Adolf Krebs in 1937.
• Involves oxidation of Acetyl Co A to CO₂ and H₂O.
• Enzymes of the cycle are located in mitochondrial matrix.

2. TCA cycle

• Starts with acetyl CoA and oxaloacetate to form citrate.
• The conversion of pyruvate to acetyl CoA is the link between glycolysis and citric acid cycle.

3. Summary of TCA cycle

Acetyl CoA + 3 NAD⁺ + FAD + GDP + Pi + 2H₂O è 2CO₂+ 3NADH + 3H⁺ + FADH₂ + GTP + CoA

4. Importance of TCA cycle

The TCA cycle has both the catabolic and anabolic significance.

i) Catabolic importance

The net gain of ATP in one TCA cycle is 12 ATP as follows:

3NADH	=	9 ATP
FADH2	=	2 ATP
GTP	=	1 ATP
Net Gain	=	12 ATP

ii) Anabolic importance

Many intermediates of the citric acid cycle are drawn off as precursors in many biosynthetic pathways for the synthesis of many useful compounds like amino acids, fatty acids, purines, pyrimidines etc as shown in figure.

5. Regulation of TCA cycle

• Accumulation of NADH and FADH2 è Inhibition of TCA cycle
• Enzymes which regulate TCA cycle
• 1) Citrate synthase
• Inhibited by ATP, NADH, acetyl CoA, and succinyl CoA
• 2) Isocitrate dehydrogenase
• Activated by ADP
• Inhibited by ATP and NADH
• 3) α-ketoglutarate dehydrogenase
• Inhibited by NADH and succinyl CoA