CLONING AND NUCLEOTIDE-SEQUENCE OF A FULL-LENGTH CDNA FOR HUMAN LIVER GAMMA-GLUTAMYLCYSTEINE SYNTHETASE

We have cloned and sequenced a full-length cDNA for human liver γ-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in glutathione biosynthesis. The cDNA consists of 2634 bp containing an open reading frame encoding a protein of 367 amino acids and having a calculated Mr = 72,773. The nucleotide sequence of the cDNA for human liver GCS shares an 84% overall similarity with the composite rat GCS sequence deduced from three overlapping partial cDNAs (Yan and Meister, JBC 265: 1588-1593, 1990). The deduced amino acid sequences are 94% similar. Comparison of Northern blots of total RNA isolated from rat kidney or liver with that from human kidney revealed the GCS mRNA to be larger in the human tissue (∼4.0 kb vs. ∼3.7 kb). (The sequence for the human liver GCS cDNA has been assigned accession number M90656 in GenBank/EMBL databases.). © 1992 Academic Press, Inc.