Citric Acid Cyle (CAC): The major catabolic pathway for acetyl-CoA in aerobic organisms.

Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with H2O, and oxidized to CO2 with the release of reducing equivalents (2H). -Acetyl-CoA is an intermediate product and CAC is amphibolic metabolism.

form citrate (6-carbon) by citrate synthase [Enzyme Classification 6: Ligases] y Forming carbon-carbon bond between methyl carbon of acetyl-coA and cabonyl carbon of oxaloacetate y The thioester bond of citrylCoA is hydrolyzed, releasing citrate and CoASH, which is an exergonic reaction Exergonic reaction, a favorable reaction which is a release of energy 2. Citrate is isomerized to isocitrate (6carbon)by aconitatehydratase [EC 4: Lyases] y Aconitase employs a dehydrationhydration mechanism. Dehydration of citrate to cis-aconitate then rehydration to isocitrate Isocitrate undergoes dehydrogenation to form alpha-ketoglutarate (5 carbon), which is catalyzed by isocitratedehydrogenase [EC 1:Oxidoreductases; Red-Ox Reaction]

CAC is the final pathway for oxidation of carbohydrates, proteins, and lipids, whose common end metabolite is acetyl-CoA

For one turn of the cycle, 11 ~P are generated via oxidative phosphorylation and 1 ~P arises at substrate level from the conversion of succinyl-CoA to succinate. There are 12~P created in entire CAC.

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Acetyl coA (2-carbon) and oxaloacetate (4-carbon) is catalyzed to

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Succinyl-CoA is converted to succinate by succinatethiokinase or succinylCoAsynthatase [ C 6: igases] y Subtrate-level phosphorylation occurs; ADP ATP (1 ATP produced) Succinate undergoes dehydrogena tion to make a carbon-carbon double bond, forming fumarate (4-Carbon catalyzed by succinatedeh drogenase [ C 1: Oxidoreductases; Red-Ox reaction] y Succinatedehydrogenase is bound in the inner surface of the inner mitochondrial membrane y Requires FAD+ and iron-sulfur protein as coenzyme y FAD+ FADH + HFumarate is added with water to remove the carbon double bond by fumarase or fumaratehydratase [ C 4: Lyases; hydration then dehydration] forming LMalate (4-Carbon L-Malate is converted to oxaloacetate (4carbon by malatedeh drogenase [ C 1: Oxidorecductases; Red-Ox reaction] y It requires coenzyme NAD+ (NAD+dependent); NAD+ NADH + H y Release of 2 HOxaloacetate is again catalyzed with AcetylCoA by citrate synthase, and will undergo the entire Citric Acid cycle y The velocity of the entire cycle may depend on the number/ availability of OXALOAC TATE, since there are more acetyl-CoA present in intracellular

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Alpha- etoglutarate undergoes oxidative decarboxylation to form succinyl-CoA. This process is catalyzed by multi-enzyme complex alphaketoglutaratedeh drogenase complex [ C 1: Oxidoreductases; Red-Ox Reaction] y Cofactors: thiamine diphosphate, lipoate, NAD+, FAD and CoA y NAD+ NADH+H-; release of 2 H- and received by NAD+ y The release of CO2 makes succinyl-CoA a 4-Carbon molecule.

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It requires c enzyme NAD+ (N + ependent); N + N H + H Release of 2 HIs citrate bec mes enzyme bound with isocitratedehydrogenase and initially form oxalsuccinate Then decarboxylation (removal of C ; 1 carbon) forming alphaetoglutarate.The decarboxylation process requires Mn2+ or Mg2+ ions.

COMPUTATION OF ATP: The reduced coenzymes NADH and FADH will undergo oxidative phosphorylation in the electron transport chain to be oxidized The release of energy during the oxidative process of these coenzyme will be used for the phosphorylation of ADP forming ATPs. 1 NADH + H - 3 ATPs 1 FADH + H - 2 ATPs In Krebs Cycle: 3 NADH + H - 9 ATPs 1. isocitrate alpha-ketoglutarate 2. alpha-ketoglutarate succinyl-CoA 3. L-malate oxaloacetate 1 FADH + H - 2 ATPs 1. Succinate fumarate y There are 8 H- (Hydride ions)/ electrons/ reducing equivalent

Subsequent oxidation of 2H in the respiratory chain (Electron Transport Chain) leads to coupledphosphorylation of ADP to ATP. Total ATPs generated in 1 Krebs Cycle: 9 ATPs (from NADH + H) 2 ATPs (from FADH + H) 1 ATP (from substrate phosphorylation: Succinyl-CoA Succinate) 12 ATPs produce in 1 Acetyl -CoA (Krebs Cycle)

Amino Acid: Aspartic Acid (removal of NH3) Oxaloacetate y 0 ATP produced: The energy generated is not from the oxaloacetate. It only increase the concentration of oxaloacetate to increase the Acetyl CoA being processed in Citric Acid Cycle. alpha-

Glutamic Acid (removal of NH3) ketoglutarate y 9 ATPs produced:

(1)alpha-ketoglutarate succinyl-CoA [NADH+H- = 3ATPs] (2) Succinyl-CoA Succinate [Substrate Level Phosphorylation =1ATP] (3)Succinate fumarate [FADH+H- = 2ATPs] (4)L-malate oxaloacetate [NADH+H- = 3ATPs]