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

Abstract

SummaryThe methionine salvage pathway, also called the 5 0 -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 0 -methylthioribose-1-phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5 0 -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.

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

“…The methionine salvage pathway is a highly conserved pathway for converting 5′-methylthioadenosine (MTA; Pubchem 439176), a byproduct of polyamine synthesis derived from S-adenosylmethionine (SAM; Pubchem 34755), back to methionine (Pubchem 6137) ( Fig. 4A) (40). To determine if APIP was required for methionine salvage, viability was measured in cells provided either methionine or MTA as the source of methionine.…”

Recycling of Methylthioadenosine Is Essential for Normal Vascular Development and Reproduction in Arabidopsis

“…MTA Binds NA Synthase, Spd Synthase, Spm Synthase, and Tspm Synthase MTA is known to inhibit PA synthetic enzyme activities while increasing S-adenosyl-Met decarboxylase activity (Albers, 2009). For example, mammalian Spm synthase and Spd synthase activities are MTA sensitive (Pegg et al, 1981;Wu et al, 2008).…”

“…The Met recycling pathway (or Yang cycle) is present in all types of organisms, where its primary role is to recycle sulfur-containing metabolites (Albers, 2009). In most plants, bacteria, and protozoa, 5#-methylthioadenosine nucleosidase (MTN; EC 3.2.2.16) irreversibly hydrolyses 5#-methylthioadenosine (MTA) to methylthioribose (MTR) and adenine (Fig.…”

Identification of altered pathways in Down syndrome-associated congenital heart defects using an individualized pathway aberrance score

“…ADI1 has also been reported to be affected by fecundity, through the regulation of methionine metabolism (Chou et al, 2014). The methionine salvage pathway, also called the MTA cycle, is a sequential pathway comprising six reactions, which is responsible for the creation of methionine from MTA, a byproduct of polyamine biosynthesis in nearly all organisms (Albers, 2009). Downregulated or decelerated synthesis of methionine has been reported as a pathogenic mechanism causing dementia in DS (Regland and Gottfries, 1992).…”