Human 5′-Nucleotidase: Multiple Molecular Forms and Regulation

Abstract

The ability to rapidly degrade purine nucleotides to uric acid in man under experimental conditions suggests that there may be important regulatory mechanisms to maintain a constant intracellular nucleotide environment. This has been illustrated by the rapid infusion of 50 grams of fructose in man which leads to a 35% increase in the serum uric acid within 30 minutes (1). The basis for this abrupt rise in the serum uric acid is a decrease in hepatic ATP and inorganic phosphate following the phosphorylation of fructose to fructose-1-P. There is a resultant increased synthesis of AMP and IMP and a release from inhibition of the catabolic pathways leading from these nucleotides to uric acid. The purine ribonucleotide catabolic pathways to uric acid include a dephosphorylation step in which purine nucleoside monophosphates are hydrolyzed to the corresponding nucleosides and inorganic phosphate. One important enzyme catalyzing this reaction is 5′-nucleotidase. The regulation of the human enzyme has not previously been evaluated in detail (for review see reference 2). We have prepared this enzyme from human placental microsomes and studied its properties (2,3).