Citric acid cycle / TCA Citric acid cycle / TCA cyclecycle

Citric acid cycle / TCA Citric acid cycle / TCA cyclecycle

Citric acid cycle

• Krebs cycle,tricarboxylic acid.• A series of reactions in mitochondria oxidize

acetyl Co-A reduced coenzymes reoxidation in respiratory chain

• Functions:-The final common pathway for aerobic oxidation of carbohydrate, lipid, protein-A central role :

1. gluconeogenesis2. lipogenesis 3. interconversion of amino acids

Citric acid cycle

Citric acid cycle• Started with condensation of acetyl coA

with oxaloacetate to form citrate two molecules of CO2 released and oxaloacetate regenerated

• Oxaloacetate catalytic role• Enzymes: citrate synthase, aconitase,

isocitrate D-ase, ketoglutarate D-ase complex, succinate thiokinase, succinate D-ase, fumarase and malate D-ase

Citric acid cycle

• Acetyl coA + Oxaloacetate + H2OCitrate + coA + H+.

• Citrate ↔ Cis aconitate + H2O• Cis aconitate + H2O ↔ Isositrate

• Isositrate + NAD+ ↔ αKetoglutarate + CO2 + NADH

• α-Ketoglutarate + NAD+ + CoA ↔Succinyl coA + CO2+NADH

• Succinyl coA + Pi + GDP ↔ Succinate + GTP + coA.

• Succinate + FAD ↔ Fumarate + FADH2.

• Fumarate + H2O ↔ Malate• Malate + NAD+ ↔ Oxaloacetate +

NADH + H+

Citric acid cycle• Result of oxidations: 3 NADH and FADH2

in one turn of cycle• 1 ATP or GTP formed by substrate level

phosphorylation• B vitamins involved:

- riboflavin- niacin - thiamin - pantothenic acid

• Riboflavinto form FAD cofactor in the α-ketoglutarat deh. Complex & Succinate deh.

• Niacinto form NADcoenzyme for isocitrate deh.,α-ketoglutarat deh.,malate deh.

• ThiaminThiamin diphosphate coenzyme for decarboxylation in the α-ketoglutarat deh.

• Panthothenic acid as part of coA, cofactor attached to active carboxylic acid residues (acetyl coA, Succinyl coA)

Roles in matabolism• Amphibolic oxidative and synthesis

processes1. Gluconeogenesis: all intermediates

potentially glucogenic (give rise to OA production of glucose)

• Substrates for gluconeogenesis:- lactate- glycerol- glucogenic amino acids- propionate

Roles in matabolism2. Transamination by aminotransferase:

a source of carbon skeletons for synthesis of some amino acids reversible form some intermediates from these amino acids:-aspartate + pyruvate OA + alanine-glutamate + pyruvate keto glut + alanine

3. Acetyl coA is the major building block for long chain fatty acid synthesis

Citric Acid Regulating• Depends on : NAD+,FAD, ADP• Key enzimes :

Citrate synthaseisocitrate dehydrogenase,α ketoglutarat dehydrogenase