PDH Complex and TCA Cycle –
Inhibition & Regulation
Presented by: [Your Group Name]
Guided by: [Professor’s Name]
Institution: [Your College Name]
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
Pyruvate Dehydrogenase (PDH)
Complex – Overview
• • Converts pyruvate to Acetyl-CoA
• • Location: Mitochondrial matrix
• • Reaction: Pyruvate + NAD⁺ + CoA → Acetyl-
CoA + COā‚‚ + NADH
• • Coenzymes: TPP, Lipoic Acid, CoA, FAD, NAD⁺
Structure of PDH Complex
• • E1: Pyruvate Dehydrogenase (TPP)
• • E2: Dihydrolipoamide Acetyltransferase
(Lipoic Acid, CoA)
• • E3: Dihydrolipoamide Dehydrogenase (FAD,
NAD⁺)
Regulation of PDH Complex
• • PDH Kinase inhibits PDH (Activated by ATP,
NADH, Acetyl-CoA)
• • PDH Phosphatase activates PDH (Activated
by Ca²⁺, Insulin)
Inhibition of PDH Complex
• • Thiamine Deficiency (Beriberi, Wernicke-
Korsakoff)
• • Heavy Metal Poisoning (Arsenic inhibits
Lipoic Acid)
• • Excess ATP, NADH, Acetyl-CoA (Negative
Feedback)
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 FADHā‚‚,
1 GTP, 2 COā‚‚
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
Inhibition of TCA Cycle
• • Fluoroacetate inhibits Aconitase
• • NADH inhibits multiple enzymes
• • High ATP inhibits cycle
Clinical Correlations
• • PDH Deficiency → Lactic Acidosis
• • Vitamin B1 Deficiency → Affects PDH & TCA
Cycle
• • Arsenic Poisoning → Inhibits Lipoic Acid
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
References
• • Vasudevan, D. M. – Textbook of
Biochemistry for Medical Students
• • Satyanarayana U. – Biochemistry
• • Harper’s Illustrated Biochemistry
• • Lippincott’s Illustrated Reviews:
Biochemistry

PDH_TCA_Cycle_Presentation.pptx citric acid cycle

  • 1.
    PDH Complex andTCA Cycle – Inhibition & Regulation Presented by: [Your Group Name] Guided by: [Professor’s Name] Institution: [Your College Name]
  • 2.
    Introduction • • Importanceof 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 + COā‚‚ + NADH • • Coenzymes: TPP, Lipoic Acid, CoA, FAD, NAD⁺
  • 4.
    Structure of PDHComplex • • E1: Pyruvate Dehydrogenase (TPP) • • E2: Dihydrolipoamide Acetyltransferase (Lipoic Acid, CoA) • • E3: Dihydrolipoamide Dehydrogenase (FAD, NAD⁺)
  • 5.
    Regulation of PDHComplex • • PDH Kinase inhibits PDH (Activated by ATP, NADH, Acetyl-CoA) • • PDH Phosphatase activates PDH (Activated by Ca²⁺, Insulin)
  • 6.
    Inhibition of PDHComplex • • Thiamine Deficiency (Beriberi, Wernicke- Korsakoff) • • Heavy Metal Poisoning (Arsenic inhibits Lipoic Acid) • • Excess ATP, NADH, Acetyl-CoA (Negative Feedback)
  • 7.
    Overview of TCACycle (Krebs Cycle) • • Location: Mitochondrial matrix • • Function: Final common pathway for oxidation of carbohydrates, fats, and proteins • • Products per Acetyl-CoA: 3 NADH, 1 FADHā‚‚, 1 GTP, 2 COā‚‚
  • 8.
    Regulation of TCACycle • • 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 TCACycle • • 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 • • PDHComplex 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