On Chemistry and Function of Coenzyme

In recent years, the nutritional importance of the vitamins has been amplified by the understanding of their metabolic function. It appears rather clearly that every vitamin functions in what may be called a distinct metabolic territory. It is shaped for a special metabolic function by its particular chemical nature. In return, the identification of this special functioning of the various chemical individuals which we call "vitamins" has recently shed considerable light into many metabolic processes. Specifically, with pantothenic acid, we have been able, during the last halfdozen years, to amplify the pioneer work of Roger Williams (74, 75). We have found a specific metabolic territory for the pantothenic acid through, I would say, a number of fortunate accidents. During the study of a relatively simple, so-called "detoxication reaction", the acetylation of aromatic amines in liver extracts, we observed the need of a heat-stable cofactor (36, cf. also 18, 48) which did not seem to coincide with any then known coenzyme. Eventually, on isolation of this new coenzyme, it was found to contain pantothenic acid (21). The discovery of pantothenic acid in the coenzyme, to which we gave the name "coenzyme A (CoA)", was greatly facilitated through help from Dr. Roger Williams' laboratory, in particular, by Dr. Beverly Guirard. She analyzed the material which we submitted, and it was through her skilful observations that pantothenic acid was detected in the coenzyme (21, 38). When bound in CoA, pantothenic acid appeared unavailable to most test organisms, including the most commonly used, Lactobacilua arabinosus. To identify it, Guirard hydrolyzed the coenzyme with acid and determined fl-alanine by yeast growth. These observations prompted us to develop a method for the liberation of pantothenic acid from CoA by a double enzymic treatment, namely, with intestinal phosphatase and with an initially unidentified liver enzyme (51). The thus established connection of pantothenic acid with our seemingly offthe-road acetylation reaction was the clue that we were dealing here with a phenomenon of primary metabolic importance. On the other hand, isotope studies had demonstrated amply that a so far rather mysterious metabolic unit called "active acetate" or "active 2-carbon residue" was an intermediary which operated as a building stone in a large number of synthetic reactions (5, 6). When, soon after the discovery of CoA, a great variety of acetylation reactions ap-