Hypoxanthine-guanine phosphoribosyltransferase deficiency and erythrocyte synthesis of pyridine coenzymes

Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, wi th virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activ ity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis fr om nicotinic acid (nicotinic acid phosphoribosyltransferase : NAPRT, and NA D synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax . The rate of synthesis of pyridine nucleotides from nicotinic acid by inta ct erythrocytes in vitro was also increased in most patients. These finding s suggest that raised NAD concentrations in HPRT- erythrocytes are due to e nhanced syhthesis as a result of increased enzyme activities.