Im a bit confused about this article \"Growth and Metastases of Human Lung Cance
ID: 165376 • Letter: I
Question
Im a bit confused about this article "Growth and Metastases of Human Lung Cancer Are Inhibited in Mouse Xenografts by a Transition State Analogue of 5'-Methylthioadenosine Phosphorylase" (MTAP).
The drug MTDIA was introduced as a transition state analog to inhibt the MTAP enzyme, but I thought that MTAP enzyme was essential in salvaging adenine & methionine and in polyamine metabolism, as well has preventing the accumulation of methylthioadenosine (MTA)..
What is the purpose of introducing a transition state analog, like MTDIA, and what affect will it actually have on the enzyme?
Explanation / Answer
Transition state analogs can be act as inhibitors in enzyme-catalyzed reactions, which can block the all active site of the enzyme. These inhibitors bind more tightly to the enzyme than compared to the actual substrate. Mice treated with transition state analog showed increased MTA and decreased polyamines with slight alteration in the methionine or adenine levels. Hence, this is considered as potent antitumor activity (MTDIA) against lung cancer.