Deduced Amino Acid Sequence from Human Phosphoribosylpyrophosphate Synthetase Subunit II cDNA

Abstract

5-Phosphoribosyl 1-pyrophosphate (PRPP) is a primary substrate in the de novo and salvage pathways of the biosyntheses of purine, pyrimidine, and pyridine nucleotides [1]. It also serves as a regulatory substrate for amidophosphoribosyltransferase and as a critical activator for carbamoylphosphate synthetase II [2], key enzymes of the purine and pyrimidine de novo syntheses, respectively. In man, abnormalities of this enzyme were reported, which causes hyperuricemia and eventually gout [3–7], This disease was transmitted as an X-linked trait, and, in fact, this PRPP synthetase gene was mapped to the human chromosome Xq22–q26, using human enzyme-specific antibody [8]. Recently we showed that rat PRPP synthetase has two distinct types of subunits, referred to as PRS I and PRS II, by cDNA cloning [9] and N-terminal amino acid sequencing [K. Kita et al., in this volume]. Studies with human and mouse somatic cell hybrids showed that human PRS I and PRS II genes were both located on different regions of the human chromosome X [10]. Superactivity of PRPP synthetase was categorized into five groups by Becker et al. [11]. However, the complex cases were reported: for instance, B-lymphoblast lines derived from individuals with the excessive maximal reaction velocity (catalytic defects) of this enzyme in erythrocytes, fibroblasts, and lymphocytes do not express the superactive phenotype [12]. This phenomenon may be caused by the presence of the two genes for this enzyme. For the precise analysis of the human PRPP synthetase genes and their abnormalities, we have attempted to clone cDNAs of the human enzyme. In this paper, we reported the cloning of cDNA for human PRPP synthetase subunit II and the deduced amino acid sequence.