Catabolism and lability of S-adenosyl-l-methionine in rat liver extracts

Abstract

The fate of S-adenosyl-L-methionine was studied in rat liver extracts by analysing the distribution of radioactivity from labelled adenosylmethionine in decomposition products, which were separated from each other by chromatographic and electrophoretic means. Marked non-enzymic degradation to adenine, pentosylmethionine, methylthioadenosine and homoserine was evident at pH 6.9-7.8. Enzymic cleavage to methylthioadenosine was stoichiometric with the accumulation of spermidine and could be totally prevented by inhibiting S-adenosyl-L-methionine decarboxylase. The results rule out the existence of adenosylmethionine cyclotransferase in rat liver and indicate that only two quantitatively significant enzymic processes are involved in hepatic adenosylmethionine degradation. Excluding nonenzymic decomposition, more than 99% of adenosylmethionine is demethylated and exclusively catabolized further by S-adenosyl-L-homocysteine hydrolase. Less than 1% of adenosylmethionine is decarboxylated and immediately utilized totally for polyamine biosynthesis.

Unbiased Metabolite Profiling Indicates That a Diminished Thymidine Pool Is the Underlying Mechanism of Colon Cancer Chemoprevention by Alpha-Difluoromethylornithine

“…Indeed, it has been reported that 1-5% of SAM is directed to polyamine biosynthesis in healthy cells, with the remainder directed towards 1-carbon transfer reactions, including synthesis of methionine and thymidine for protein and DNA synthesis, respectively (33-36). Thus, decreased SAM levels may effectively limit the availability of SAM for use by metabolic pathways, including regulation of THF cofactor availability (37-39).…”

S-Adenosylmethionine regulates connexins sub-types expressed by hepatocytes

“…In the liver, S-Adenosylmethionine (SAMe) is a precursor of glutathione and polyamine synthesis, and it serves as a methyl donor in cellular transmethylation reactions (Eloranta and Kajander, 1984). Methionine Adenosyltransferase (MAT) catalyzes the formation of SAMe from methionine and ATP (Finkelstein, 1990; Mato, et al, 1997).…”

Inhibition of juvenile hormone III biosynthesis in cockroach corpora allata by interference with the S‐adenosylmethionine‐dependent transmethylation

“…6), as it is in most eucaryotic cells. For instance, virtually all AdoHcy produced in rat liver is catabolized by AdoHcy hydrolase [34]. We have no direct evidence of the inhibition of the 0-methyl transferase by the accumulation of intracellular AdoHcy in our MTA experiments.…”