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Kelley WN, Rosenbloom FM, Seegmiller JE. The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism. J Clin Invest. 1967;46(9):1518-29doi: 10.1172/JCI105643.
Kelley, W. N., Rosenbloom, F. M., & Seegmiller, J. E. (1967). The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism. The Journal of clinical investigation, 46(9), 1518-29. https://doi.org/10.1172/JCI105643
Kelley, W N, et al. "The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism." The Journal of clinical investigation vol. 46,9 (1967): 1518-29. doi: https://doi.org/10.1172/JCI105643
Kelley WN, Rosenbloom FM, Seegmiller JE. The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism. J Clin Invest. 1967 Sep;46(9):1518-29. doi: 10.1172/JCI105643. PMID: 16695929; PMCID: PMC292897.
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J Clin Invest. 1967 Sep;46(9):1518-29. doi: 10.1172/JCI105643.

The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism.

The Journal of clinical investigation

W N Kelley, F M Rosenbloom, J E Seegmiller

Affiliations

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

PMID: 16695929 PMCID: PMC292897 DOI: 10.1172/JCI105643

Abstract

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.

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