Mechanisms in Intracellular Turnover of Stable and Labile Enzymes

摘要

The authors have focused on two proteins of rat liver, one representative of the stable class and probably of reaction mechanisms operative in degradation of all proteins, the other unusually labile and possibly subject to uncommon as well as common mechanisms in turnover. The proteins chosen, tyrosine aminotransferase (E.C. 2.6.1.5) and alanine aminotransferase (E.C. 2.6.1.2) are similar in many respects. They catalyze similar reactions and share a substrate pair (glutamic acid and alpha -ketoglutarate). Both are located in the soluble fraction of liver cytoplasm. Molecular weights are comparable (tyrosine aminotransferase, 100,000; alanine aminotransferase, 115,000) and both enzymes are structurally dimers of apparently identical subunits each of which binds one molecule of the common coenzyme, pyridoxal phosphate. Metabolically both are inducible by glucocorticoid hormones. But there the resemblance ends, for on the other, degradative side of the metabolic coin the two enzymes are sharply divergent. Tyrosine aminotransferase is among the most labile of liver enzymes, undergoing turnover with a half-life of 1.5 h, while turnover of alanine aminotransferase (half-life about 3 days) is virtually identical to that of the bulk of soluble liver proteins. Recent experimentation designed to determine the mechanistic basis for this difference in metabolism of otherwise quite similar enzymes is reviewed. (ERA citation 03:001426)