Enzyme defect in primary gout.
The rate-limiting step in the degradation of adenine nucleotides in the liver is the conversion of adenosine monophosphate (A.M.P.) to inosine monophosphate by A.M.P. deaminase, which is normally 95% inhibited. When the inhibition is released, uric acid is formed in large excess, and the biosynthesis of purines is increased. We therefore propose that congenital hyperuricaemia is caused by the presence of an abnormal A.M.P. deaminase, which is less sensitive to its physiological inhibitors. Verification of the hypothesis depends upon the availability of liver tissue from patients with congenital hyperuricaemia for kinetic analysis of A.M.P. deaminase. A call for collaboration is addressed to the medical community.
D000659:AMP Deaminase / Q000378:metabolism*; D003641:Deamination; D006073:Gout / Q000201:enzymology / Q000209:etiology*; D006801:Humans; D007291:Inosine Monophosphate / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009709:Nucleotide Deaminases / Q000378:metabolism*; D011685:Purine Nucleotides / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D014527:Uric Acid / Q000097:blood
D011685:Purine Nucleotides; D011687:Purines; D007291:Inosine Monophosphate; D014527:Uric Acid; D009709:Nucleotide Deaminases; D000659:AMP Deaminase