Effects of Hormones and Drugs on Activity of L-Gulono-y-Lactone Hydrolase. ∗

Summary

The temporal sequence of changes in activity of L-gulono-γ-lactone hydrolase, in concentration of ascorbic acid in serum and in urine during replacement therapy of hypophysectomized rats with somato-tropin was examined. Results agree with the view that variations in activity of the hydro-lase are responsible for diminished synthesis of ascorbic acid after hypophysectomy and increased synthetic activity when somato-tropin is administered. The prompt decrease in activity of the hydrolase found after removal of the hypophysis did not occur in severe alloxan diabetes, indicating that permissive action of insulin may not be required for effects of somatotropin on hepatic protein anabolism. However, DL-ethionine rapidly depressed the activity of the hydrolase and of L-gulonate NADP oxidoreductase in a way analogous to long-term consequences of hypophysectomy. It appears that an alternative to the step involving lactonization of L-gulon-ic acid cannot be quantitatively important for synthesis of ascorbic acid. Inhibition of the hydrolase by Chloretone and chloral hydrate in vitro, in apparent contradiction since these drugs stimulate biosynthesis of ascorbic acid, is probably of no relevance in vivo.