The Effects of Azathioprine (Imuran) on Purine Synthesis in Clinical Disorders of Purine Metabolism

William N. Kelley; Frederick M. Rosenbloom; J. Edwin Seegmiller

doi:10.1172/JCI105643

Section on Human Biochemical Genetics, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland

‡

Address requests for reprints to Dr. J. Edwin Seegmiller Section on Human Biochemical Genetics, 10-8D19, National Institute of Arthritis and Metabolic Diseases, Bethesda, Md. 20014.

Submitted for publication 27 March 1967; accepted 7 June 1967.

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Section on Human Biochemical Genetics, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland

‡

Address requests for reprints to Dr. J. Edwin Seegmiller Section on Human Biochemical Genetics, 10-8D19, National Institute of Arthritis and Metabolic Diseases, Bethesda, Md. 20014.

Submitted for publication 27 March 1967; accepted 7 June 1967.

Find articles by Rosenbloom, F. in: PubMed | Google Scholar

Section on Human Biochemical Genetics, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland

‡

Address requests for reprints to Dr. J. Edwin Seegmiller Section on Human Biochemical Genetics, 10-8D19, National Institute of Arthritis and Metabolic Diseases, Bethesda, Md. 20014.

Submitted for publication 27 March 1967; accepted 7 June 1967.

Find articles by Seegmiller, J. in: PubMed | Google Scholar

Published in Volume 46, Issue 9 on September 1, 1967
J Clin Invest. 1967;46(9):1518–1529. https://doi.org/10.1172/JCI105643.
© 1967 The American Society for Clinical Investigation

Published September 1, 1967 - Version history

Azathioprine, a purine analogue, significantly suppressed the purine synthesis de novo of two gouty patients manifesting overproduction of uric acid, as well as three of four gouty patients who showed normal uric acid production. This suppression is taken as evidence that phosphoribosyl-pyrophosphate amidotransferase, the rate-controlling step in purine synthesis de novo, has a normal sensitivity to feedback inhibitors in the patients who responded to the drug.

Two children afflicted with the familial disorder of hyperuricemia, choreo-athetosis, and self-mutilation described by Lesch and Nyhan showed no reduction in the activity of the biosynthetic pathway in response to azathioprine. This inability to respond to azathioprine can be directly related to the absence in these patients of the enzyme hypoxanthine-guanine phosphoribosyltransferase which is required for conversion of the drug or its metabolites to the biochemically active ribonucleotide form.