Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine

Abstract

The methionine salvage pathway, also called the 5'-methylthioadenosine (MTA) cycle, recycles the sulfur of MTA, which is a by-product in the biosyntheses of polyamine and the plant hormone ethylene. MTA is first converted to 5'-methylthioribose-1-phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5'-methylthioribose kinase. Subsequently, five additional enzymatic steps, catalyzed by four or five proteins, will form 4-methylthio-2-oxobutyrate, the deaminated form of methionine. The final transamination is achieved by transaminases active in the amino acid biosynthesis. This pathway is present with some variations in all types of organisms and seems to be designed for a quick removal of MTA achieved by high affinities of the first enzymes. During evolution some enzymes have attained additional functions, like a proposed role in nuclear mRNA processing by the aci-reductone dioxygenase. For others the function seems to be lost due to conditions in specific ecological niches, such as, presence of sulfur and/or absence of oxygen resulting in that, for example, Escherichia coli is lacking a functional pathway. The pathway is regulated as response to sulfur availability and take part in the regulation of polyamine synthesis. Some of the enzymes in the pathway show separate specificities in different organisms and some others are unique for groups of bacteria and parasites. Thus, promising targets for antimicrobial agents have been identified. Other medical topics to which this pathway has connections are cancer, apoptosis, and inflammatory response.