BIOCHEMICAL STUDIES OF HUMAN HYPERURICAEMIA

Abstract

Some of the enzymes involved in the biosynthesis of uric acid have been investigated in two groups of patients: hyperuricaemic and gouty individuals. A group of normal controls has been used for comparison. Human erythrocyte phosphoribosylpyrophosphate synthetase (2.7.6.1.) was found to be much more stable in all samples than has been reported. Kinetic parameters for this enzyme, using a modified assay, were identical in individuals from the three clinical groups. Inhibition studies using a range of inhibitors of widely differing chemical structure showed uniformity in characteristics amongst gouty or healthy individuals. Some inhibitors revealed possible genetic variants of the enzyme which are linked neither to hyperuricaemia nor to gout. Statistical analyses have shown a significant increase in the enzymic activity of erythrocyte phosphoribosylpyrophosphate synthetase in both the hyperuricaemic groups compared with the controls. No correlation of age with enzymic activity occurs in any of the three clinical groups. A significant decrease has been found for the enzymic activity of erythrocyte glutathione reductase (1 .6.4 .2.) of thee gout group compered w:ith the other two groups. The activities of these two enzymes do not appear to be linked. A significant increase in serum adenosine deaminase (3.5.4.4.) activities has been found in a heterogeneous hyperuricaemic group compared with controls. Electrophoretic studies of erythrocyte phosphoribosylpyrophosphate synthetase, adenosine deaminase, hypoxanthineguanine phosphoribosyltransferase (2.4.2.8.) and glutathione reductase have shown probable enzyme polymorphisms which appear to be unrelated to hyperuricaemia or gout. Modified staining techniques have been developed for the detection of isoenzymes in all systems. There is no evidence for urate binding to plasma proteins in either healthy or hyperuricaemic individuals from occlusion, ultrafiltration, electrophoresis or gel filtration experiments. Urate appears to be present in human leucocytes combined to protein or other component of the cell. There is no evidence of the presence of urate in human erythrocytes.