Disease relevance of oxalacetic acid

• We report here a new mode of coupling between the chemical and vectorial reaction explored for the oxaloacetate decarboxylase Na+ pump from Klebsiella pneumoniae [1].
• Transcarboxylase is a 1.2 million Dalton (Da) multienzyme complex from Propionibacterium shermanii that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate to yield propionyl-CoA and oxaloacetate [2].
• We have identified and characterized lambda bacteriophage clones containing genomic DNA encoding rat malic enzyme [(S)-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating); EC 1.1.1.40] [3].
• Bovine kidney aldolase shows no stereospecificity in catalyzing the aldol cleavage of the two optical isomers of 2-keto-4-hydroxyglutarate, and although it also catalyzes the beta-decarboxylation of oxalacetate, its decarboxylase/aldolase activity ratio is lower than that seen with the pure enzyme from either bovine liver or Escherichia coli [4].
• The metabolic pathways for the interconversion of oxalacetate, phosphoenolpyruvate, and pyruvate in Pseudomonas citronellolis form an interlocking system (Scheme 1) that would appear to require complex regulatory mechanisms to permit a proper flow of metabolites through the pathways and to prevent futile cycling [5].

High impact information on oxalacetic acid

• Here we report the synthesis of rationally designed polypeptides that catalyse the decarboxylation of oxaloacetate via an imine intermediate [6].
• Here we have studied the effect of vanadate on malate dehydrogenase (MDH, EC1.1.1.37) catalysed oxidation of NADH during the formation of malate from oxalacetate in vitro [7].
• The structure reveals a dimer of beta(8)alpha(8) barrels with an active site cobalt ion coordinated by a carbamylated lysine, except in the oxaloacetate complex in which the product's carboxylate group serves as a ligand instead [2].
• Transcarboxylase from Propionibacterium shermanii is a 1.2 MDa multienzyme complex that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate, yielding propionyl-CoA and oxaloacetate [8].
• Aspartate 203 of the oxaloacetate decarboxylase beta-subunit catalyses both the chemical and vectorial reaction of the Na+ pump [1].

Chemical compound and disease context of oxalacetic acid

• This parallel loss of binding affinities for oxaloacetate and alpha-ketoglutarate, in two mutants altered in residues at the active site of E. coli citrate synthase, strongly suggests that inhibition of this enzyme by alpha-ketoglutarate is not allosteric but occurs by competitive inhibition at the active site [9].
• The alpha-subunit was 60% identical with the carboxyltransferase domain of rat liver propionyl-CoA carboxylase, the beta-subunit showed 61% sequence identity with the beta-subunit of oxaloacetate decarboxylase from Klebsiella pneumoniae, and the biotin-containing gamma-subunit was 29-39% identical with biotin-domains of other biotin enzymes [10].
• ATP-dependent phosphoenolpyruvate carboxykinase (PEPCK) (ATP: oxaloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) is a key enzyme involved in the catabolism of glucose and amino acids in the parasite Trypanosoma cruzi, the causative agent of Chagas' disease [11].
• The four half-transamination reactions [the pyridoxal form of Escherichia coli aspartate aminotransferase (AspAT) with aspartate or glutamate and the pyridoxamine form of the enzyme with oxalacetate or 2-oxoglutarate] were followed in a stopped-flow spectrometer by monitoring the absorbance change at either 333 or 358 nm [12].
• Kinetic mechanism of Escherichia coli isocitrate dehydrogenase and its inhibition by glyoxylate and oxaloacetate [13].

Biological context of oxalacetic acid

• Moreover, the formation of the complex between IclR and the operator/promoter region has been found to be impaired by phosphoenol pyruvate but insensitive to acetate, acetyl-CoA, pyruvate, and oxaloacetate [14].
• Uptake rates of 0.1 mM citrate and alpha-ketoglutarate were inhibited by greater than 90% by 10 mM succinate, malate, fumarate, or oxaloacetate, indicating the presence in the brush border membrane of a transport system highly specialized for the renal conservation of intermediates of the tricarboxylic acid cycle [15].
• Complementary DNA clones encoding human cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) (PEPCK)] were isolated from a human kidney cDNA library [16].
• We isolated the gene for citrate synthase (citrate oxaloacetate lyase; EC 4.1.3.7) from Saccharomyces cerevisiae and ablated it by inserting the yeast LEU2 gene within its reading frame [17].
• The first branch point in gluconeogenesis occurs at the conversion of pyruvate to oxaloacetate [18].

Anatomical context of oxalacetic acid

• Under these conditions subsequent swelling and Mg2+ loss are inhibited.l Ultrastructural observations show the mitochondria become permeable in response to Ca2+ plus oxalacetate or Ca2+ plus t-butyl hydroperoxide in a heterogeneous manner [19].
• As a result of an attempt to clarify the physiological importance of oxaloacetate tautomerase activity, keto-oxaloacetate was demonstrated to be directly transported across the inner membrane of rat liver mitochondria on the basis of the results of kinetic and isotope-trapping experiments [20].
• The Na+-pumping oxaloacetate decarboxylase, isolated from Klebsiella aerogenes membranes, was incorporated into the membranes of lecithin liposomes [21].
• The oxaloacetate is converted to malate which exits the mitochondrion, where, in the cytosol, it is decarboxylated to pyruvate in the reaction catalyzed by malic enzyme [22].
• The liver glucose-6-phosphatase of intact microsomes is inhibited and displays sigmoid kinetics in the presence of alpha-ketoglutarate-magnesium and oxaloacetate-magnesium chelates [23].

Associations of oxalacetic acid with other chemical compounds

• They function in the metabolism of the di- and tricarboxylates malate and citrate, mostly in fermentative pathways involving decarboxylation of malate or oxaloacetate [24].
• While sugar catabolism proceeds mainly via oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation, respectively [25].
• The lack of inhibition by Mg2+ suggests that the physiological regulation of the plant channel may differ from IMAC and that the plant IMAC may have functions such as a role in the malate/oxaloacetate shuttle in addition to its proposed role in volume homeostasis [26].
• This model of "substrate channeling" (or alternatively a direct transfer of oxalacetate between enzymes) is supported by experiments with excess aspartate aminotransferase and glutamate added to the solution phase to give a reaction competing with the synthase for bulk phase oxalacetate [27].
• The shift in the curve relating J glucose to oxalacetate is due to glucagon-induced inhibition of pyruvate kinase [28].

Gene context of oxalacetic acid

• In a previous study [Bernstine, E.G. (1979) J. Biol. Chem. 254, 83-87] it was shown that inbred strains of mice fall into two classes based on the specific activity of mitochondrial malic enzyme [L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 1.1.1.40] in brain [29].
• Pyruvate carboxylase (PC) is a biotinylated mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate [30].
• These results agreed with the role of PckTk in providing phosphoenolpyruvate from oxaloacetate as the first step of gluconeogenesis in this hyperthermophilic archaeon [31].
• Kinetic parameters (Km and kcat) obtained for all four substrates (aspartate, alpha-ketoglutarate, glutamate, and oxaloacetate) were consistent with values obtained for native AAT isoenzymes from other plant species [32].
• This method is based on the in-frame fusion of both a polyhistidine tail and a 100-amino acid residue biotin acceptor domain of oxaloacetate decarboxylase from Klebsiella pneumoniae at the carboxyl terminus end of Pgp (Pgp-H6BD) [33].

Analytical, diagnostic and therapeutic context of oxalacetic acid

• The course of reductive titrations appears the same whether or not the enzyme contains oxalacetate, and complete reduction as monitored by bleaching of chromophoric groups requires the incorporation of 6 to 7 reducing equivalents in either case [34].
• Two active site missense mutants of this enzyme, generated by oligonucleotide-directed mutagenesis, have lower affinities for one substrate, oxaloacetate, but also are much less sensitive to 2-oxoglutarate, an oxaloacetate analogue hitherto believed to be an allosteric inhibitor [35].
• It was found by HPLC that the decarboxylation of alpha-ketoglutarate (KGL), pyruvate (PYR), and oxaloacetate (OA) by both oxidants results in the formation of succinate, acetate, and malonate, respectively [36].
• 3. A partial purification of the NAD-linked "malic" enzyme from Glossina was effected by DEAE-cellulose chromatography, which separated the enzyme from malate dehydrogenase and NADP-linked "malic" enzyme, but not from oxaloacetate decarboxylase [37].
• Purification of the sodium transport enzyme oxaloacetate decarboxylase by affinity chromatography on avidin sepharose [38].

References