Disease relevance of ACONITIC ACID

• A novel methyltransferase catalyzes the methyl esterification of trans-aconitate in Escherichia coli [1].
• Emendation of the description of Acidaminococcus fermentans, a trans-aconitate- and citrate-oxidizing bacterium [2].
• Decreases in blood magnesium in turn cause a potentially fatal disease known as grass tetany. trans-Aconitate was stoichiometrically reduced to tricarballylate by Selenomonas ruminantium, a common ruminal bacterium in grass-fed ruminants (J. B. Russell, Appl. Environ. Microbiol. 49:120-126, 1985) [3].

High impact information on ACONITIC ACID

• Overexpression of the o252 gene resulted in an overexpression of the methyltransferase activity, and we have now designated it tam for trans-aconitate methyltransferase [1].
• Since trans-aconitate does not appear to be a metabolic intermediate in these cells but forms spontaneously from the key citric acid cycle intermediate cis-aconitate, we suggest that its methylation may limit its potential interference in normal metabolic pathways [1].
• We demonstrate the endogenous formation of trans-aconitate methyl ester in extracts of wild type but not tam- mutant cells indicating that trans-aconitate is present in E. coli [1].
• Crystal structures of mitochondrial aconitase with the inhibitors trans-aconitate and nitrocitrate bound to the [4Fe-4S] cluster have been solved and refined at 2.05 A resolution with R-factors of 0.168 and 0.172, respectively [4].
• Although trans-aconitate is a minor endogenous substrate of the Tmt1 enzyme in extracts of S. cerevisiae, the major endogenous substrate has yet to be identified [5].

Biological context of ACONITIC ACID

• We have identified the yeast open reading frame YER175c as the gene encoding the trans-aconitate methyltransferase of Saccharomyces cerevisiae [6].
• The Tmt1 methyltransferase recognizes (2R,3S)-3-isopropylmalate with similar kinetics as it does trans-aconitate, with respective K(m) values of 127 and 53 microM and V(max) values of 59 and 70 nmol min(-1) mg(-1) of protein in a Tmt1-overexpressed yeast extract [5].
• Ruminal fluid which was enriched with trans-aconitate yielded a gram-negative diplococcus (strain AO) which was identified by 16S ribosomal DNA sequence analysis as Acidaminococcus fermentans [2].

Anatomical context of ACONITIC ACID

• Finally, we demonstrated that the activity of the yeast trans-aconitate methyltransferase is localized in the cytosol and increases markedly as cells undergo the metabolic transition at the diauxic shift [6].

Associations of ACONITIC ACID with other chemical compounds

• 3-Isopropylmalate is the major endogenous substrate of the Saccharomyces cerevisiae trans-aconitate methyltransferase [5].
• When mixed ruminal bacteria were incubated in vitro with 10 mM trans-aconitate for 24 h, 45% of the trans-aconitate was converted to tricarballylate [3].
• Thiamine was extracted from samples by mild acid digestion (trans aconitate pH 4.0) at 115 degrees C for 20 min [7].

Gene context of ACONITIC ACID

• We now designate this gene TMT1 for trans-aconitate methyltransferase [6].
• It has been proposed that methylation may attenuate trans-aconitate inhibition of aconitase and other enzymes of the cycle [5].

References