S-methyl-5'-thioadenosine phosphorylase (MTAP) is an enzyme responsible for polyaminemetabolism. In humans, it is encoded by the methylthioadenosine phosphorylase (MTAP) gene on chromosome 9.[5] Multiple alternatively spliced transcript variants have been described for this gene, but their full-length natures remain unknown.[6]
This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine. It is responsible for the first step in this pathway, where it catalyzes the reversible phosphorylation of MTA to adenine and 5-methylthioribose-1-phosphate. This takes place after MTA is generated from S-adenosylmethionine.[5]
An additional role of MTAP has been found in the protozoan parasite Trypanosoma brucei, which causes African trypanosomiasis (sleeping sickness). The T. brucei MTAP has an unusually broad specificity and can cleave MTA as well as adenosine and deoxyadenosine.[7] The cleavage of deoxyadenosine serves as a protection mechanism to avoid the accumulation of toxic levels of dATP in the parasite (dATP is formed form deoxyadenosine). The cleavage activity has also consequences for drug discovery against African trypanosomiasis. It is important that adenosine analogues developed against the parasite are resistant to cleavage to be effective.[8]
MTAP was identified for the first time and characterized likely as a phosphorylase in 1969 by Pegg and Williams-Ashman.[9] The first purification that allowed characterization was by a group in 1986.[10] This purification allowed researchers to investigate why there is the lower expression of MTAP in some types of cancer.
Increased levels of MTA in tumor cells along with lower expression of MTAP.[11] The enzyme is deficient in many cancers because this gene and the tumor-suppressive p16 gene are co-deleted.[11][12][13][14][15]
