Biochemical genetic analysis of the role of methylthioadenosine phosphorylase in a murine lymphoid cell line.

摘要: The enzyme methylthioadenosine phosphorylase functions in both purine and polyamine metabolism is dividing mammalian cells. To determine the effects of loss this on cell growth metabolism, we selected two phosphorylase-deficient mutant clones transplantable murine T lymphoma line R1.1. first had 3.5% wild type activity. second was completely enzyme-deficient. did not alter rate, cloning efficiency, or tumor-forming ability excreted substantial amounts into culture medium (0.13 0.32 nmol/h/mg protein, respectively) were unable to utilize substrate 2',5'-dideoxyadenosine as a source when de novo synthesis blocked. Spermine levels 10-20% lower enzyme-deficient than rendered mutants exquisitely sensitive antiproliferative methylthioadenosine. Methylthioadenosine at 3-6 microM inhibited their by 50%. toxic attributable inhibition purine, pyrimidine, synthesis.