Disease relevance of S-Methyl-alpha-ketobutyric acid

• By using these methods 4-methylthio-2-oxobutanoate, a putative intermediate in the biosynthesis of ethylene from methionine, has been identified in culture fluids of Aeromonas hydrophila B12E and a coryneform bacterium D7F grown in the presence of methionine [1].
• A photochemical assay developed for 4-methylthio-2-oxobutanoate shows it to be a product of the metabolism of methionine by Escherichia, Pseudomonas, Bacillus, Acinetobacter, Aeromonas, Rhizobium and Corynebacterium species [1].
• An aminotransferase which catalyzes the final step in methionine recycling from methylthioadenosine, the conversion of alpha-ketomethiobutyrate to methionine, has been purified from Klebsiella pneumoniae and characterized [2].

High impact information on S-Methyl-alpha-ketobutyric acid

• The increase in free Met and S-methylmethionine levels in these mutants, together with in vitro substrate specificity, strongly implicate BCAT4 in catalysis of the initial deamination of Met to 4-methylthio-2-oxobutyrate [3].
• The addition of the penultimate salvage pathway compound 4-methylthio-2-oxobutanoic acid represses ODC levels in both MTAP-deleted yeast and human tumor cell lines, indicating that 4-methylthio-2-oxobutanoic acid acts as a negative regulator of polyamine biosynthesis [4].
• The data also show that rat kidney cytosolic glutamine transaminase K catalyzes both a beta-elimination and a transamination reaction with DCVC when alpha-keto-gamma-methiolbutyrate is present and that amino acid oxidase and alpha-keto-gamma-methiolbutyrate stimulate the enzyme activity by providing amino acceptors [5].
• The free radical scavengers mannitol, thiourea, benzoate, and 4-methylmercapto-2-oxobutyrate protected either native cells exposed to H2O2 or pretreated hepatocytes exposed to H2O2 and given ferric or ferrous iron [6].
• The method is based on the gas chromatographic detection of ethylene, which is formed by the reaction of alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC) with ROS [7].

Biological context of S-Methyl-alpha-ketobutyric acid

• Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex [8].
• Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells [9].
• Phosphorylation of PDC is decreased by 2-oxobutyrate, but not by 4-methylthio-2-oxobutyrate [8].
• Kinetics and effects of trace elements and electron complexes on 2-keto-4-methylthiobutyric acid-dependent biosynthesis of ethylene in soil [10].
• With the view of evaluating the relative utilization of methionine isomers, the pulmonary exhalation of dimethyl sulfide and methyl mercaptan and the urinary excretion of alpha-keto-gamma-methiolbutyrate were studied in normal healthy subjects following oral or intravenous administration of L- or D-isomer of methionine [11].

Anatomical context of S-Methyl-alpha-ketobutyric acid

• Phosphorylation of BCOADC in isolated adipocytes is inhibited by both 4-methylthio-2-oxobutyrate and 2-oxobutyrate, consistent with their inhibitory action of BCOADC kinase [8].
• The decarboxylation of alpha-keto-gamma-methiolbutyrate in rat liver mitochondria [12].
• The rate of conversion to 2-keto 4-methylthiobutanoic acid (KMB) was highest for DL-MET and lowest for L-MET in kidney, liver and intestinal mucosa [13].

Associations of S-Methyl-alpha-ketobutyric acid with other chemical compounds

• These results suggest that benzoate decarboxylation might serve as a more specific probe to detect the presence of .OH than either 4-methylmercapto-2-oxobutyrate or ethanol, which react readily with .OR [14].
• No such features of apoptosis were found in cells treated with 4-methylthio 2-oxobutanoic acid or propanal, suggesting that the simultaneous presence of the methylthio group on the propanal moiety is essential for apoptosis to take place [9].
• The ability of lactoferrin to catalyse hydroxyl radical production was determined by measuring ethylene production from methional (2-amino-4-methylthiobutyraldehyde) or 4-methylthio-2-oxobutyrate [15].
• Decarboxylation of both alpha-ketoisocaproate and alpha-keto-gamma- methiolbutyrate by liver increased significantly within one-half hour after rats had ingested either the 9 or the 50% casein diet [16].
• The purified enzyme also exhibited glutamine transaminase K activity with phenylalanine and alpha-keto-gamma-methiolbutyrate as substrates [17].

Gene context of S-Methyl-alpha-ketobutyric acid

• 4-Methylthio-2-oxobutanoic acid is the direct precursor of methional, which is a potent inducer of apoptosis in a BAF3 murine lymphoid cell line which is interleukin-3 (IL3)-dependent [9].
• This is not explained by a direct inhibition of glutaminase by 4-methylthio-2-oxobutyrate but by a substrate competition between glutaminase and glutamine transaminases [18].

Analytical, diagnostic and therapeutic context of S-Methyl-alpha-ketobutyric acid

• Partial purification of the enzyme system by gel exclusion chromatography to remove small molecular weight substrates and cofactors revealed that synthesis of 2-keto-4-methylthiobutyrate requires magnesium and is inhibited by calcium [19].

References