Molecular cloning and nucleotide sequence of cDNA for human liver arginase.

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Abstract
Arginase (EC 3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme resulted in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, we isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in .lambda.gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated .lambda.hARG6 and .lambda.hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted Mr 34,732), a 5''-untranslated sequence of 56 base pairs, a 3''-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying .lambda.hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat and yeast enzymes.