Coenzyme A, An Acyl Group Carrier and Activator

Coenzyme A, named for its role as an acetyl group carrier, contains the vitamin pantothenic acid as an essential constituent (Fig. 10). The synthesis of this vitamin can be accomplished by green plants, fungi, and most bacteria, but not by the human body. Its unusual chemical structure provides the necessary shape and chemical properties to allow it to bind into crevices within the active sites of a variety of proteins. There it not only fits snugly but has electrostatic bonding interactions that allow the proteins to hold it in just the correct orientation for its function. Curiously, the exact biological need for the unusual structure of the vitamin is still obscure. The chemically functional end of coenzyme A is the sulfhydryl (—SH) group which is added on to the vitamin structure by cells, as shown in Fig. 10. Before coenzyme A can function it must be combined in a thioester linkage with a carboxylic acid such as acetic acid, or a long-chain fatty acid, as illustrated in Fig. 10 (right). It is customary in discussions of metabolism to indicate the bulk of the coenzyme structure as CoA. The free coenzyme is designated CoA—SH, and in a thioester the hydrogen of the —SH group is replaced by an acyl group. The coenzyme has two functions. First, it can carry the acyl group from one protein to the next in a metabolic sequence, such as that of Fig. 12. Second, it can activate a hydrogen atom adjacent to the carbonyl (C=O) group for removal of a proton (H+) by a catalytic group of basicnature, suchas —NH2, present intheprotein. Thecarbonyl group in a thioester is an electron accepting group, whose facilitation of the proton removal is often indicated by curved arrows, as shown in Fig. 10 (right). The product of this proton removal is a reactive anion which is able to undergo formation or cleavage of carbon–carbon bonds or dehydrogenation by the riboflavin-containing FAD, as shown in Fig. 12.

Other coenzymes and prosthetic groups may also act as acyl group carriers. For the biosynthesis of fatty acids, a shortened version of coenzyme A (phosphopantetheine, Fig. 10), is covalently linked to appropriate proteins. During carbohydrate metabolism, a prosthetic group consisting of bound lipoic acid (Fig. 11) carries acetyl groups. Both acetyl groups and long-chain fatty acyl groups are carried across membranes into and out of mitochondria while attached to the unusual amino acid carnitine (Fig. 4). Carnitine is not a vitamin but acts as a coenzyme.