Disease relevance of hydroxypyruvic acid

• The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II [1].
• Structural, kinetic, and renaturation properties of an induced hydroxypyruvate reductase from Pseudomonas acidovorans [2].
• Two crystal forms of hydroxypyruvate reductase (D-glycerate dehydrogenase) from the methylotrophic bacterium Hyphomicrobium methylovorum have been grown from ammonium sulphate solutions [3].
• A BLAST search using as the query sequence the hydroxypyruvate/glyoxylate reductase from Cucumis sativus identified as an orthologue the yiaE gene of E. coli encoding a ketoaldonate reductase [4].
• Pyruvate decarboxylase from Zymomonas mobilis is inhibited by 3-hydroxypyruvate, which can also act as a poor substrate [5].

High impact information on hydroxypyruvic acid

• Kinetic and spectroscopic data indicated that addition of the donor substrate hydroxypyruvate to the thiamin diphosphate (ThDP)-dependent enzyme transketolase (TK) led to the accumulation of the alpha-carbanion/enamine of (alpha,beta-dihydroxyethyl) ThDP, the key reaction intermediate in enzymatic thiamin catalysis [6].
• In particular, hydroxypyruvate is effectively reduced by the enzyme, the reaction rate, and Km value being comparable to those in the case of pyruvate, indicating that the enzyme has not only D-lactate dehydrogenase activity but also D-glycerate dehydrogenase activity [7].
• A hydroxypyruvate reductase has been induced in Pseudomonas acidovorans by growth on glyoxylate [2].
• Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase [8].
• A tryptophan residue (Trp141) from the neighbouring subunit of the dimer is projected into the active site region and appears to contribute to the selectivity for hydroxypyruvate [8].

Chemical compound and disease context of hydroxypyruvic acid

• Other dehydrogenases associated with the metabolism of meso-tartrate in Pseudomonas putida, such as hydroxypyruvate reductase and tartronate semialdehyde reductase, were also shown to be A-specific [9].
• In a previous paper, we reported identification of the 5' part of hprA of Methylobacterium extorquens AM1, which encodes the serine cycle enzyme hydroxypyruvate reductase (L. V. Chistoserdova and M. E. Lidstrom, J. Bacteriol. 174:71-77, 1992) [10].
• We suggest that 3-phosphoserine oxoglutarate transaminase in normal E. coli serves as a catalyst for transaminating small amounts of serine to 3-hydroxypyruvate, which is then used in pyridoxine biosynthesis [11].

Biological context of hydroxypyruvic acid

• Light regulates alternative splicing of hydroxypyruvate reductase in pumpkin [12].
• However, the present results indicate that hydroxypyruvate also functions in an almost identical manner, which implies that alkylation of a susceptible nucleophile cannot be the mechanism responsible for the covalent attachment of the anion [13].
• The immediate product of the pyruvate kinase catalyzed phosphorylation of beta-hydroxypyruvate is the enol of tartronate semialdehyde phosphate (TSP) [14].
• Kinetics and inhibitory studies of the enzyme from M. extorquens AM1 suggest that hydroxypyruvate reductase is not a site for regulation of the serine cycle at the level of enzyme activity [15].
• Two full-length cDNAs encoding hydroxypyruvate reductase were isolated from a cDNA library constructed with poly(A)+ RNA from pumpkin green cotyledons [16].

Anatomical context of hydroxypyruvic acid

• Hydroxypyruvate as a gluconeogenic substrate in rat hepatocytes [17].
• Pumpkin hydroxypyruvate reductases with and without a putative C-terminal signal for targeting to microbodies may be produced by alternative splicing [16].
• Alternative oxidase in durum wheat mitochondria. Activation by pyruvate, hydroxypyruvate and glyoxylate and physiological role [18].
• With both intact and shocked peroxisomes the intermediates glyoxylate and hydroxypyruvate did not equilibrate with the medium [19].
• Hydroxypyruvate decarboxylase activity was found mainly in the mitochondria, with the remainder (25%) in the cytosol [20].

Associations of hydroxypyruvic acid with other chemical compounds

• Oxalate as a potent and selective inhibitor of spinach (Spinacia oleracea) leaf NADPH-dependent hydroxypyruvate reductase [21].
• In the pre-steady-state, no reaction intermediates typical of PLP enzymes were observed with the substrates L-serine, glyoxylate, and hydroxypyruvate [22].
• The effect of dichloroacetate and hydroxypyruvate on the entry of 14C from [1-14C]alanine into urea in rat hepatocytes [23].
• Transcriptional regulation of hydroxypyruvate reductase gene expression by cytokinin in etiolated pumpkin cotyledons [24].
• In isolated hepatocytes the entry into urea of metabolic 14CO2 derived from [14C] formate is modified by the addition of dichloroacetate and hydroxypyruvate [25].

Gene context of hydroxypyruvic acid

• In order to understand the nature of this intermediate, we have determined the three-dimensional structure of N-acetylneuraminate lyase in complex with hydroxypyruvate (a product analogue) and in complex with one of its products (pyruvate) [26].
• Cloning and overexpression of the ycdW gene showed that its product displayed a high NADPH-linked glyoxylate reductase activity, and also catalysed the reduction of hydroxypyruvate with a lower efficiency [4].
• The NADH-dependent hydroxypyruvate reductase from cucumber and the pdxB gene product of E. coli display significant homology to E. coli D-3-phosphoglycerate dehydrogenase [27].
• The Km for hydroxypyruvate (with NADPH) was about 0.8 mM in the pH range 5.5-6.5, and 0.3 mM at pH 8 [28].
• This mutant had lost its ability to grow on C-1 compounds but retained the ability to grow on C-2 compounds, showing that the hydroxypyruvate reductase operating in the serine cycle is not involved in the conversion of acetyl coenzyme A to glycine as previously proposed [29].

Analytical, diagnostic and therapeutic context of hydroxypyruvic acid

• Rabbit antibodies prepared against NADPH(NADH)-hydroxypyruvate reductase were highly specific for this enzyme and did not cross-react with peroxisomal NADH(NADPH)-dependent hydroxypyruvate reductase, as found by Western immunoblots of proteins from leaf extracts of spinach, pea and wheat [28].
• Isolation, characterization and sequence analysis of a full-length cDNA clone encoding NADH-dependent hydroxypyruvate reductase from cucumber [30].
• Immunodiffusion studies indicated that serine-glyoxylate aminotransferase and hydroxypyruvate reductase of all seven Hyphomicrobium strains tested were immunochemically similar [31].
• Both pyruvate and beta-hydroxypyruvate were used as substrates and the enantiomeric excess was analyzed by a combination of NMR, circular dichroism and chiral-column gas chromatographic methods [32].
• Radioactive isotope dilution and high-performance liquid chromatography analysis revealed the autooxidation of hydroxypyruvate to oxalate on standing in buffered solution at pH 7 [33].

References