TCA Cycle Presented By, Mrs. Lincy Joseph Asst. Prof

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TCA Cycle Presented By, Mrs. Lincy Joseph Asst. Prof College of Nursing Kishtwar

History Discovered by Hans Krebs in 1937 He received the Nobel Prize in physiology or medicine in 1953 for his discovery Forced to leave Germany prior to WWII because he was Jewish

Most of cells energy comes from oxidation of A.CoA in mitochondria Glycolysis oxidizes sugar to pyruvate which is converted to A.CoA in mitochondria Proteins and fatty acid are also broken down to yield A.CoA Acetyl units oxidized to CO2 in mitochondrial matrix by TCA cycle Energy released during oxidation captured by NAD+ and FAD > Carried to ETC for synthesis of ATP (oxidative phosphorylation)

Pyruvate + CoA + NAD+ A. CoA + CO2 + NADH + H+ RXN 10 Glycolysis Pyruvate produced from glycolysis must be decarboxylated to A. CoA before it enters TCA cycle Catalyzed by large enzyme Pyruvate dehydrogenase complex (mitochondrial matrix) Pyruvate + CoA + NAD+ A. CoA + CO2 + NADH + H+

Control of the Pyruvate Dehydrogenase complex Regulation by its products > NADH & Acetyl-CoA : inhibit While >NAD+ & CoA stimulate Regulation by energy charge > ATP : inhibit > AMP : stimulate

Glucose Pyruvate Acetyl CoA CO2 Lipids

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

Acetyl CoA Citrate Isocitrate -ketoglutarate oxaloacetate malate Succinyl CoA (4C) (4C) Fumarate Succinate (4C) (4C)

Acetyl CoA Citrate Isocitrate oxaloacetate -ketoglutarate malate NAD oxaloacetate CO2 NADH NADH -ketoglutarate NAD NAD malate CO2 Succinyl CoA NADH Fumarate GDP FADH2 Succinate GTP FAD

Regulation of Citric Acid Cycle 3 Control sites

Regulation of Citric Acid Cycle con’t Site 1 - rxn 1 Acetyl CoA + Oxaloacetate Citrate Enzyme: citrate synthase Inhibited by ATP

Regulation of Citric Acid Cycle con’t Site 2 - rxn 3 Isocitrate -Ketoglutarate Enzyme: isocitrate dehydrogenase Inhibited by ATP & NADH Stimulated by ADP & NAD+

Regulation of Citric Acid Cycle con’t Site 3 - rxn 4 -Ketoglutarate Succinyl CoA Enzyme: -Ketoglutarate dehydrogenase Similar to PDH complex Inhibited by Succinyl CoA & NADH also high-energy charge.

Regulation of Citric Acid Cycle Summary IN GENERAL THE TCA CYCLE IS INHIBITED BY A HIGH ENERGY CHARGE AND STIMULATED BY LOW ENERGY CHARGE

Overview Glycolysis produces pyruvate by oxidation of glucose The pyruvate is than oxidized to A.CoA in the mitochondria The acetly units are oxidized to CO2 by TCA cycle in the mitochondrial matrix Energy released during both the oxidation rxns are collected by NAD+ and FAD So NADH and FADH2 carry energy in the form of electrons

Where do all the NADH’s and FADH2’s Go