Human renal C-S lyase: structure-activity relationships of cytosolic and mitochondrial enzymes

Abstract

The enzyme cysteine conjugate /.I-lyase (C-S lyase, EC 4.4.1.13) from rat renal tissue has been identified as a transaminase: glutamine transaminase K (GTK) [l]. This is one member of a family of enzymes which effect a transamination reaction on amino acid substrates. Other members of this family include glutamine transaminase L (GTL, isolated from rat liver, but which has a structure-activity profile broadly overlapping that of GTK), kynurenine aminotransferase (KAT), and aspartate aminotransferase. Rat hepatic cytosolic C-S lyase co-purifies as kynureninase, an enzyme which is involved in anthranilic acid biosynthesis [2], but antibodies raised against this purified protein did not crossreact with the renal cytosolic enzyme (i.e. with GTK). In one study with human hepatic cytosolic C-S lyase [3], kynurenine was not a substrate for the enzyme. These workers did not establish whether the C-S lyase enzyme had a physiological role, and if it co-purified with a protein which had been previously characterized. We have recently established that human hepatic cytosolic C-S lyase co-purifies as an aminotransferase: KAT [4]. In this article, we discuss the structureactivity relationships displayed by human C-S lyases obtained from both the cytosolic and mitochondrial sub-cellular fractions of kidney, liver and lung tissue. Elsewhere