Reactions of the Citric Acid Cycle:- Why Is the Oxidation of Acetate So Complicated?
The eight-step cyclic process for oxidation of simple two carbon acetyl groups to CO2 may seem unnecessarily cumbersome and not in keeping with the biological principle of maximum economy. The role of the citric acid cycle is not confined to the oxidation of acetate, however.
This pathway is the hub of intermediary metabolism. Four- and five-carbon end products of many catabolic processes feed into the cycle to serve as fuels. Oxaloacetate and -ketoglutarate, for example, are produced from aspartate and glutamate, respectively, when proteins are degraded. Under some metabolic circumstances, inter mediates are drawn out of the cycle to be used as pre cursors in a variety of biosynthetic pathways. The citric acid cycle, like all other metabolic path ways, is the product of evolution, and much of this evolution occurred before the advent of aerobic organisms. It does not necessarily represent the shortest pathway from acetate to CO2, but it is the pathway that has, over time, conferred the greatest selective advantage. Early anaerobes most probably used some of the reactions of the citric acid cycle in linear biosynthetic processes. In fact, some modern anaerobic microorganisms use an in complete citric acid cycle as a source of, not energy, but biosynthetic precursors . These organisms use the first three reactions of the cycle to make α-ketoglutarate but, lacking α-ketoglutarate dehydrogenase, they cannot carry out the complete set of citric acid cycle reactions. They do have the four enzymes that catalyze the reversible conversion of oxaloacetate to succinyl-CoA and can produce malate, fumarate, succinate, and succinyl-CoA from oxaloacetate in a reversal of the “normal” (oxidative) direction of flow through the cycle. This pathway is a fermentation, with the NADH produced by isocitrate oxidation recycled to NAD+ by reduction of oxaloacetate to succinate. With the evolution of cyanobacteria that produced O2 from water, the earth’s atmosphere became aerobic and organisms were under selective pressure to develop aerobic metabolism, which, as we have seen, is much more efficient than anaerobic fermentation.
