The citric acid cycle (CAC, Krebs Cycle)
This oxidative cycle serves as a melting pot for the products of carbohydrate, fat, and protein metabolism after initial catabolism in separate pathways. Even though it is sometimes considered as a pa thway of glucose oxidation because of the carbohydrate nature of its intermediates, the citric acid cycle does not discriminate on the basis of the origin of its substrates. Furthermore, the catabolism of several amino acids also provides intermediates for the cycle.
The key compound that channels the carbons of glucose, amino acids, and fatty acids into the cycle is acetyl CoA (or active acetate). The condensation of acetyl CoA with oxaloacetic acid initiates the series of reactions that result in the oxidation of the two acetate carbons into CO2, with regeneration of Co A and oxaloacetic acid (OAA). Even though OAA is not used up in the cycle, its supply can become limiting for the oxidation of acetyl CoA because there are other uses for OAA, as is shown in the subsequent sections. OAA is produced from carboxylation of pyruvate by a biotin-dependent pyruvate carboxylase and is plentiful when carbohydrates are actively metabolized. Catabolism of certain amino acids also replenishes the supply of the CAC intermediates and is especially important when the supply of carbohydrates is limited.
The energy generated in the oxidative steps (dehydrogenations) of the cycle is utilized in the concomitant reduction of coenzymes NAD+ (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) and thereby conserved as reducing equivalents (NADH + H+ and FADH2). This energy can then be reclaimed by reoxidation of the coenzymes in the respiratory chain, or it may be directly used in synthetic reactions involving reductive steps specific for these coenzymes.
