5Methylthioadenosine

5'-Methylthioadenosine, commonly abbreviated MTA, is a naturally occurring purine nucleoside consisting of adenine attached to a ribose sugar with a thioether substituent at the 5' position of the sugar. It is produced as a byproduct of polyamine biosynthesis when decarboxylated S-adenosylmethionine transfers an aminopropyl group to putrescine to form spermidine (and, subsequently, spermine).

Metabolism and salvage pathways

In many organisms, MTA is cleaved by the enzyme 5'-methylthioadenosine phosphorylase (MTAP) to produce adenine and 5-methylthioribose-1-phosphate. The resulting ribose-phosphate derivative can feed into the methionine salvage pathway, ultimately contributing to methionine and S-adenosylmethionine regeneration. In humans, MTAP is encoded by the MTAP gene, and MTAP activity links purine and methionine metabolism through the salvage pathway. MTAP deficiency or deletion can lead to accumulation of MTA in cells.

Biological significance

MTA can act as a regulator of cellular methylation reactions by inhibiting several S-adenosylmethionine-dependent methyltransferases, including members of the protein arginine methyltransferase family. Because MTAP is frequently lost or downregulated in cancers, intracellular MTA levels can influence methylation balance and have been studied for potential therapeutic implications, including sensitization to methyltransferase inhibitors.

Occurrence

MTA is widely distributed across organisms and is formed as a routine byproduct of polyamine biosynthesis in bacteria, plants, fungi, and animals. It is also a subject of biochemical and pharmacological research due to its roles in metabolism and methylation regulation.