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 results 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.