MTA phosphorylase

Experiments were also carried out injecting [3 -3H]xylosyl-MTA. The results indicated that the molecule has a very low turnover rate in D. verrucosa, since 96% of the recovered radioactivity after 24 h was associated with xylosyl-MTA. Accordingly, it was observed [126] that xylosyl-MTA is resistant to the enzyme MTA-phosphorylase which cleaves MTA but not the xylose analog, which therefore accumulates in the animal. Since xylosyl-MTA is mainly concentrated in the hermaphrodite gland of D. verrucosa and is very abundant in the eggmasses [103], it may play a role in the reproductive biology of D. verrucosa. 

FIG. 55 Methionine salvage pathway via 5 -methylthioadenosine (MTA). 1, MTA phosphorylase 2, MTA nucleosidase 3, 5-methylthioritese kinase. 

The purine requirement for this enzyme is unknown and it is likely that an AdoMet analog based on purine or methionine could affect both polyamine and methylation reactions. In trypanosomatids, the salvage enzyme methylthioadenosine (MTA) phosphorylase has been found to have a broad substrate requirement (Fig. 7.1)... 

MTA phosphorylase is the main enzyme responsible for the degradation of the thioether in mammalian tissues. It prevents the cellular accumulation of MTA and plays a primary role in purine salvage the reaction (pathway 4) involves the phosphorolytic cleavage of the glycosidic bond(Z/Df MTA and the release of methylthioribose-l-phos-phate (MTR-l-P) and adenine. 

The occurrence of MTA phosphorylase in Caldatiella acjdophila a thermophilic bacterium growing optimally at 87 C, represents the only example of a phosphorolytic cleavage of MTA in prokaryotes. 

In Fig. 6 is compared the effect of temperature on the reaction rate of MTA phosphorylase purified from Caldariella acidophila and human placenta. As observed in many other enzymes from thermophilic microorganisms,the phosphorylase from Caldariella acidophila shows a remarkable thermophilic ty with an optimum temperature at 95 C while the same enzyme from human tissues displays an optimum of activity at 65 C. 

Two structural analogues of MTA are endowed with antimitotic activity the 7-deaza analogue, methylthiotubercidin (MTT) and 5 -isobutylthioadenosine (SIBA). MTT exerts a potent irreversible inhibition on lympocytes stimulated by various mitogens. This analogue is also a competitive inhibitor of MTA phosphorylase purified from human27 and rat prostate. ... 

In our opinion, however, the structure of SIBA is more closely related to MTA than to Ado cy and therefore the enzymes involved in MTA metabolism could be the most probable targets for the drug action. It is interesting to mention, in this respect, that SIBA is actively metabolized in mammalian tissues by MTA phosphorylase which converts the molecule into isobutylthioribose—1- phosphate and adenine . The affinity of the drug towards this enzyme is even in the natural substrate. 

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