Response of Phosphopyruvate Carboxylase to Tryptophan Metabolites and Metal Ions

Abstract

Tryptophan, administered to rats, inhibits gluconeogenesis, but increases the activity of hepatic phosphopyruvate carboxylase when assayed in vitro. Quinolinate, a metabolite of tryptophan, inhibits gluconeogenesis in perfused livers, and inhibits phosphopyruvate carboxylase in liver cytosol from tryptophan‐treated rats but not from normal rats. Metal‐ion activation and quinolinate inhibition of hepatic cytosol phosphopyruvate carboxylase has been investigated in vitro. Of the cations tested, only Fe2+, Co2+, Cd2+ and Mn2+ appreciably increased this enzymic activity. Quinolinate inhibited the activity of divalent cation‐treated enzyme in the order Co2+ Fe2+ Cd2+ and did not inhibit the Mn2+‐treated phosphopyruvate carboxylase. Other tryptophan metabolites, metal chelators, and structural analogs of quinolinate have been tested, but only quinolinate lowered the activity of the Fe2+‐treated enzyme substantially. The elevated phosphopyruvate carboxylase activity in cytosol of tryptophan‐treated rats was lowered in vitro by quinolinate to the same extent as was the activity of the Fe2+‐treated enzyme from normal rats. Ferrous iron is proposed as the physiologically important cation and quinolinate the important metabolite responsible for altering the activity of phoshopyruvate carboxylase in vivo following tryptophan administration. Copyright © 1971, Wiley Blackwell. All rights reserved