A review: biological and clinical aspects of pyrimidine metabolism.

Abstract

Interest in pyrimidine nucleotide biosynthesis has stemmed largely from the importance of these molecules as components of nucleic acids. Regulation of pyrimidine biosynthesis has been most extensively investigated in micro-organisms in which cell division is effectively controlled by regulation of the activity of the enzymes of the d e n o v o pathway (77, 11 0). The relation between pyrimidine biosynthesis and cellular proliferation in mammals has become clearer with the accumulation of a considerable body of evidence which indicates that there is a close correlation between the activity of enzymes involved in pyrimidine biosynthesis and the rate of cellular proliferation. The d e n o v o pyrimidine biosynthetic pathway and the urea cycle bo th utilize carbamyl phosphate, and important nitrogen carrier. The biosynthesis of pyrimidine and purine nucleotides are connected by a common intermediate, phosphoribosyl pyrophosphate (PRPP). In addition, pyrimidine nucleotides act as sugar and phospholipid carriers and are important in lipopolysaccharide biosynthesis. The importance of these interrelations is most forcibly emphasized by certain clinical phenomena which will be discussed later. This paper will attempt t o review the broad biologic aspects of pyrimidine nucleotide biosynthesis. A detailed consideration of d e n o v o pyrimidine biosynthesis in eucaryotic cells is available in the recent review by Jones (81). Pyrimidine biosynthesis in procaryotes has been reviewed in depth by O'Donovan and Neuhard (1 10).