In Vitro Effects of Magnesium Ions on Mutant Cells from Patients with the Lesch-Nyhan Syndrome

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Abstract
Addition of nontoxic amounts of magnesium ions to fibroblast cell cultures from patients with the Lesch-Nyhan syndrome increased both the rate of cell growth in limiting medium and the enzymatic activity of the mutant hypoxanthine-guanine phosphoribosyltransferase. Six Lesch-Nyhan strains normally resistant to the purine analogue, 8-azaguanine, became sensitive to growth-inhibitory effects of this antimetabolite when magnesium ions were added to the culture. Assay of fibroblast hypoxanthine-guanine-phosphoribosyltransferase with azaguanine-14C as substrate demonstrated that magnesium ions stimulate conversion of small amounts of the analogue to the toxic ribonucleotide in Lesch-Nyhan cell strains. Average apparent Michaelis constants for magnesium phosphoribosyl-pyrophosphate were 3.1 ± 0.8 X 10–3M and 1.9 ± 0.9 X 10–3M for control and mutant erythrocyte hypoxanthine-guanine-phosphoribosyltransferase respectively (p>0.05). Although the Lesch-Nyhan mutation does not reduce affinity of the enzyme for magnesium ions, increased magnesium levels change some of the biochemical abnormality of Lesch-Nyhan cells in culture. (N Engl J Med 289: 446–450, 1973)