5′-Deoxy-5′-Methylthioadenosine Phosphorylase Deficiency in Leukemia: Genetics and Biochemical Aspects

Abstract

In mammalian cells, 5′-deoxy-5′-methylthioadenosine (MTA) derives from decarboxylated S-adenosyl methionine during spermidine and spermine synthesis.¹ To a lesser extent, MTA Is also produced following the aminocarboxypropyl group transfer from S-adenosylmethionine to certain tRNA uridine residues² (Fig. 1). Although MTA can inhibit polyamine amlnopropyl transferase reactions³, the thioether nucleoside does not accumulate In normal cells but Is rapidly cleaved to adenine and 5-methylthioribose 1-phosphate by the enzyme MTA Phosphorylase. As shown In Figure 1, MTA Phosphorylase is important not only for the balanced synthesis of polyamlnes, but also for the economic Intracellular salvage of adenine nucleotides and methionine. ^{4, 5} The enzyme is present In all normal tissues studied thus far. Recently, we have assigned the gene for MTA Phosphorylase to the 9pter→9q12 region of human chromosome 9 by analysis of mouse-human somatic cell hybrids.