1. We have studied the metabolism of adenine and adenosine in intact erythrocytes from three children and four adults of two separate families. The children were homozygotes for a deficiency of AMP-pyrophosphate phosphoribosyltransferase (adenine phosphoribosyltransferase, EC 220.127.116.11), and the parents heterozygotes.
2. In this intact cell system at physiological concentrations of inorganic phosphate (Pi) and adenine heterozygote adenine phosphoribosyltransferase activity was normal, whereas at higher adenine concentrations (1.0–10 μmol/l) the four heterozygotes showed approximately 50% of control activity. At high concentrations of Pi (18 mmol/l) and adenine (10 μmol/l) and with extended incubation heterozygote activity was again indistinguishable from normal. Activity of the enzyme in homozygotes was negligible under all these conditions.
3. Formation of inosine 5′-monophosphate from [8-14C]hypoxanthine at high Pi concentrations was normal in both homozygotes and heterozygotes. Thus no abnormality of either of the enzymes IMP—pyrophosphate phosphoribosyltransferase (hypoxanthine phosphoribosyltransferase, EC 18.104.22.168) or phosphoribosyl pyrophosphate synthetase (ribose phosphate pyrophosphokinase, EC 22.214.171.124) was found.
4. To ascertain whether deficiency of adenine phosphoribosyltransferase was linked with enhanced conversion of adenosine into adenine nucleotides at the expense of its deamination pathways, the complete metabolism of [8-14C]adenosine was studied over the range 0.1–9.0 μmol/l. No such increase was observed for either heterozygotes or homozygotes.
5. Insignificant formation of either [8-14C]-adenine from [8-14C]adenosine or vice versa in the erythrocytes of homozygotes lacking adenine phosphoribosyltransferase but capable of forming hypoxathine from adenosine, supports the concept that adenine and adenosine are not directly interconvertible and do not utilize purine nucleoside phosphorylase (EC 126.96.36.199) in erythrocytes.
6. Measurement of erythrocyte nucleotide concentrations by high-performance liquid chromatography revealed no obvious abnormalities. ATP:ADP:AMP proportions were normal (approximately 10:1:0.1) and the total adenine nucleotide pool was at the lower limit of the normal range for both homozygotes and heterozygotes. These observations imply that deficiency of adenine phosphoribosyltransferase does not grossly affect adenine nucleotides synthesis in the erythrocyte.