The cycle starts with reaction between the acetyl moiety of acetyl-CoA and the four-carbon dicarboxylic acid oxaloacetate, forming a six-carbon tricarboxylic acid, citrate. In the subsequent reactions, two molecules of CO2 are released and oxaloacetate is regenerated (Figure 1). Only a small quantity of oxaloacetate is needed for the oxidation of a large quantity of acetyl-CoA; it can be considered as playing acatalytic role, since it is regenerated at the end of the cycle.

Fig1. The citric acid cycle, illustrating the importance of regenerating oxaloacetate to sustain the cycle.

The citric acid cycle provides the main pathway for ATP formation linked to the oxidation of metabolic fuels. During the oxidation of acetyl-CoA, coenzymes are reduced, then reoxidized in the respiratory chain, linked to the formation of ATP (oxidative phosphorylation, Figure 16–2). This process is aerobic, requiring oxygen as the final oxidant of the reduced coenzymes. The enzymes of the citric acid cycle are located in the mitochondrial matrix, either free or attached to the inner mitochondrial membrane and the crista membrane. This is where the enzymes and coenzymes of the respiratory chain are also found.

Fig2. The citric acid cycle: the major catabolic pathway for acetyl-CoA. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, enters the cycle by forming citrate, and is oxidized to CO2 with the reduction of coenzymes. Reoxidation of the coenzymes in the respiratory chain leads to phosphorylation of ADP to ATP. For one turn of the cycle, nine ATP are generated via oxidative phosphorylation and one ATP (or GTP) arises at substrate level from the conversion of succinyl-CoA to succinate.

To sustain the cycle, the number of carbons entering and leaving must be equal. A two-carbon molecule (Acetyl-CoA) combines with a four-carbon molecule (oxaloacetate) to form a six-carbon molecule (citrate). After one turn of the cycle citrate is converted back to oxaloacetate and two carbons are released as CO2 . If a metabolic pathway adds carbon to the cycle that is not though acetyl-CoA (pyruvate [C3] to oxaloacetate [C4] for gluconeogenesis) then there must be an outlet pathway to bring an equal amount of carbon out (oxaloacetate [C4] to phosphoenolpyruvate [C3]) of the cycle. The entry of carbon is called anaplerosis. The exiting of carbon is called cataplerosis. Thus to sustain the citric acid cycle anaplerosis must equal cataplerosis.

مواضيع ذات صلة

The Citric Acid Cycle Takes Part in Gluconeogenesis, Transamination, & Deamination

Reactions of The Citric Acid Cycle Generate Reducing Equivalents & CO2

Carbohydrates Occur in Cell Membranes & in Lipoproteins

Dyslipidemia and Cardiovascular Risk

Lipoprotein and Lipid Metabolism

Biomedically, Glucose is the Most Important Monosaccharide

Saccharides are Aldehyde or Ketone Derivatives of Polyhydric Alcohols

A Supply of Oxidizable Fuel is Provided in Both The Fed & Fasting States

Many Metabolic Fuels are Interconvertible

The Flux Through Metabolic Pathways Must be Regulated In A Concerted Manner

Metabolic Pathways at The Organ & Cellular Level

Pathways To Process The Major Products Of our Diet