The Mitochondrial Glycine Cleavage System: Differential Inhibition by Divalent Cations of Glycine Synthesis and Glycine Decarboxylation in the Glycine-CO₂ Exchange

Abstract

The exchange of glycine carboxyl carbon with CO₂, catalyzed by the combination of chicken liver glycine decarboxylase (P-protein) and aminomethyl carrier protein (H-protein) was markedly inhibited by various divalent cations, although extents of inhibition by individual metal ions varied considerably. Cu²⁺ and Zn²⁺, at 100 μM, inhibited the reaction almost completely, and the inhibitions by Co²⁺ and Ni²⁺ were also significant, while Mg²⁺ and Mn²⁺ did not appreciably affect the reaction. The inhibition by Zn²⁺ was competitive with both bicarbonate and H-protein and noncompetitive with glycine. Of the two reactions involved in the glycine-CO₂ exchange, decarboxylation of glycine yielding the H-protein-bound aminomethyl moiety was not significantly affected by 100 μM Zn²⁺ or Cu²⁺, but carboxylation of the H-protein-bound aminomethyl moiety to form glycine was strongly inhibited by either Zn²⁺ or Cu²⁺. Various degrees of inhibition of the glycine-CO₂, exchange by other divalent metal ions could also be accounted for by the inhibition of the carboxylation step of the exchange reaction. The primary site of the action of divalent metal ions is likely to be not P-protein but H-protein, and the binding of metal ions with the H-protein-bound intermediate of glycine decarboxylation was assumed to account for the observed marked inhibition.