Biochemsitry

1. PDH Complex and TCA Cycle –
Inhibition & Regulation
Presented by: [Your Group Name]
Guided by: [Professor’s Name]
Institution: [Your College Name]

2. Introduction
• • Importance of PDH Complex and TCA Cycle
in Metabolism
• • Role in energy production and linking
glycolysis to oxidative phosphorylation
• • Significance in aerobic respiration and ATP
generation

3. Pyruvate Dehydrogenase (PDH)
Complex – Overview
• • Converts pyruvate to Acetyl-CoA
• • Location: Mitochondrial matrix
• • Reaction: Pyruvate + NAD⁺ + CoA → Acetyl-
CoA + CO₂ + NADH
• • Coenzymes: TPP, Lipoic Acid, CoA, FAD, NAD⁺

4. Structure of PDH Complex
• • E1: Pyruvate Dehydrogenase (TPP)
• • E2: Dihydrolipoamide Acetyltransferase
(Lipoic Acid, CoA)
• • E3: Dihydrolipoamide Dehydrogenase (FAD,
NAD⁺)

5. Regulation of PDH Complex
• • PDH Kinase inhibits PDH (Activated by ATP,
NADH, Acetyl-CoA)
• • PDH Phosphatase activates PDH (Activated
by Ca²⁺, Insulin)

6. Inhibition of PDH Complex
• • Thiamine Deficiency (Beriberi, Wernicke-
Korsakoff)
• • Heavy Metal Poisoning (Arsenic inhibits
Lipoic Acid)
• • Excess ATP, NADH, Acetyl-CoA (Negative
Feedback)

7. Overview of TCA Cycle (Krebs
Cycle)
• • Location: Mitochondrial matrix
• • Function: Final common pathway for
oxidation of carbohydrates, fats, and proteins
• • Products per Acetyl-CoA: 3 NADH, 1 FADH₂,
1 GTP, 2 CO₂

8. Regulation of TCA Cycle
• • Citrate Synthase: Inhibited by ATP, NADH,
Succinyl-CoA
• • Isocitrate Dehydrogenase: Activated by ADP,
Ca²⁺; Inhibited by ATP, NADH
• • α-Ketoglutarate Dehydrogenase: Activated
by Ca²⁺; Inhibited by Succinyl-CoA, NADH

9. Inhibition of TCA Cycle
• • Fluoroacetate inhibits Aconitase
• • NADH inhibits multiple enzymes
• • High ATP inhibits cycle

10. Clinical Correlations
• • PDH Deficiency → Lactic Acidosis
• • Vitamin B1 Deficiency → Affects PDH & TCA
Cycle
• • Arsenic Poisoning → Inhibits Lipoic Acid

11. Summary
• • PDH Complex links glycolysis to TCA Cycle
• • TCA Cycle is the final oxidative pathway
• • Both pathways are tightly regulated by
energy status
• • Inhibitors include ATP, NADH, Acetyl-CoA,
heavy metals
• • Deficiencies can cause metabolic diseases

12. References
• • Vasudevan, D. M. – Textbook of
Biochemistry for Medical Students
• • Satyanarayana U. – Biochemistry
• • Harper’s Illustrated Biochemistry
• • Lippincott’s Illustrated Reviews:
Biochemistry