Glucocorticoid control of hepatic proline oxidase

Since adrenal corticosteroids are known to affect amino acid metabolism and gluconeogenesis, we examined the relationship of these hormones to hepatic proline oxidase, the mitochondrial enzyme degrading L-proline. In adrenalectomized rats hepatic proline oxidase activity decreased to about 50% of control levels within 5-6 days. This depressed activity can be restored to normal by 4 days of corticosteroid repletion. Treatment of intact rats with supraphysiologic doses of corticosteroid further elevated proline oxidase activity. The level in treated intact rats was three-fold that of adrenalectomized rats. Kinetic analysis revealed that corticosteroid increased the amount of enzyme without altering enzyme affinity for proline. Administration of a single dose of corticosteroid to either adrenalectomized or intact animals increased enzyme activities, with a lag time of less than 2 hr. The maximum effect occurred 5-6 hr following injection. Since proline degraded by this pathway can contribute carbon skeletons directly to carbohydrate, corticosteroid induction of proline oxidase may play an important role in hepatic gluconeogenesis occurring with corticosteroid action.