Studies on Substrate Induction of Serine Dehydratase of Rat Liver

Abstract

Serine dehydratase [EC 4. 2. 1. 13] was induced by feeding a synthetic diet containing L-serine as the sole source of non-essential amino nitrogen (Serine-diet). Of the non-essential amino acids tested, only L-serine caused induction, the extent of which was dependent on the serine content of the diet. From these experiments, it was concluded that induction of this enzyme by its substrate was based on the requirement of the nitrogen moiety for growth under the conditions employed. It was demonstrated that the increase in enzyme activity resulting from this Serinediet was blocked by cycloheximide. By pulse-labeling with 14C-amino acids followed by specific precipitation of the enzyme protein with the antiserum, it was confirmed that the induction of serine dehydratase was due to increased net synthesis of enzyme protein. It was also demonstrated that activation of serine dehydratase during increased gluconeogenesis, such as on treatment of adrenalectomized-diabetic rats with triamcinolone, was based on increased net synthesis of enzyme protein. Evidence was presented, however, for a difference in the biological significances of substrate, and hormonal inductions of serine dehydratase. Under hormonal control, serine is converted to sugar via pyruvic acid and the resulting ammonia is metabolized via the urea cycle. Under substrate induction, on the other hand, the α-amino group is used in formation of other non-essential amino acids needed for growth and the residual carbon skeleton may be metabolized via the TCA cycle.