The metabolism in vitro of cardiac muscle in pantothenic acid deficiency.

An important r81e for pantothenic acid in carbohydrate metabolism was suggested by studies in which pantothenic acid-deficient bacteria (1, 2) and liver (3) were observed to utilize pyruvate at rates much less than normal. The subsequent discovery of Lipmann and his colleagues that the coenzyme of acetylation (coenzyme A) (4) contained pantothenic acid (5) provided a stimulus for the reinvestigation of the rBle of this vitamin in the physiological utilization of pyruvate and acetate. In both deficient bacteria (6) and animal tissues (7) it was found that depressed pyruvate utilization was associated with decreased coenzyme A levels, and that supplementation of deficient organisms with pantothenic acid resulted in a prompt synthesis of coenzyme A, with a concomitant stimulation in pyruvate metabolism. Although liver tissue from deficient animals showed the most striking depletion of coenzyme A, with a corresponding reduction in pyruvate utilization (7), cardiac muscle from deficient rats and ducks also showed lowered coenzyme levels and a significantly depressed pyruvate metabolism. In view of previous studies from this laboratory on the effects of vitamin deficiency upon the metabolism of cardiac muscle (8, 9) it seemed of interest to study the effects of pantothenic acid deficiency upon surviving heart tissue more intensively. Because of the importance of coenzyme A in acetylations (10-12) the metabolism of both acetate and pyruvate was studied in homogenates and slices of cardiac muscle from deficient and control ducks. In order to evaluate the rates of oxidation of these compounds, radioactive pyruvate, containing Cl4 in either the carboxyl or carbony1 group, and radioactive acetate, containing Cl4 in the carboxyl group, were employed in some experiments. The results support the view that pantothenic acid as coenzyme A is concerned with the physiological oxidation of acetate and with the oxidation of the CZ fragment derived from pyruvate. A preliminary report of these experiments has been made (13).