Disease relevance of oxaldehydic acid

• Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase [1].
• Growth of Escherichia coli on acetate requires operation of the anaplerotic sequence known as the glyoxylate bypass [2].
• Identification of mutations associated with peroxisome-to-mitochondrion mistargeting of alanine/glyoxylate aminotransferase in primary hyperoxaluria type 1 [3].
• Growth of enteric bacteria on acetate as the sole source of carbon and energy requires operation of a particular anaplerotic pathway known as the glyoxylate bypass [4].
• Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides [5].

Psychiatry related information on oxaldehydic acid

• Alcohol consumption in the absence of adequate nutrition may lead to activation of the glyoxylate cycle in man [6].

High impact information on oxaldehydic acid

• Here, we show that prokaryotic- and eukaryotic-like isoforms of the glyoxylate cycle enzyme isocitrate lyase (ICL) are jointly required for fatty acid catabolism and virulence in Mycobacterium tuberculosis [7].
• These findings in fungi, in conjunction with reports that isocitrate lyase is both upregulated and required for the virulence of Mycobacterium tuberculosis, demonstrate the wide-ranging significance of the glyoxylate cycle in microbial pathogenesis [8].
• The glyoxylate cycle is required for fungal virulence [8].
• Live S. cerevisiae cells isolated from the phagolysosome are induced for genes of the glyoxylate cycle, a metabolic pathway that permits the use of two-carbon compounds as carbon sources [8].
• Increasing photosynthesis by inhibiting photorespiration with glyoxylate [9].

Chemical compound and disease context of oxaldehydic acid

• When Escherichia coli grows on acetate, the flow of isocitrate through the glyoxylate bypass is regulated, in part, through the phosphorylation of isocitrate dehydrogenase [10].
• Competition binding experiments revealed that pyruvate (which also inactivated the E. coli enzyme, Feldman, D.A., and Datta, P. (1975) Biochemistry 14, 1760-1767) did not interfere with the binding of glyoxylate or vice versa, suggesting that the two keto acids may occupy separate sites on the enzyme molecule [11].
• Biochemical characterization of recombinant proteins verified that Synechocystis harbors an active serine hydroxymethyltransferase, and, contrary to higher plants, expresses a glycolate dehydrogenase instead of an oxidase to convert glycolate to glyoxylate [12].
• The glyoxylate bypass and citric acid cycle operate concurrently in Escherichia coli when acetate is the sole source of carbon and energy to sustain aerobic growth [13].
• BACKGROUND: Primary hyperoxaluria is a rare genetic disorder of glyoxylate metabolism that results in overproduction of oxalate [14].

Biological context of oxaldehydic acid

• The amide is formed by hydroxylation of an additional glycine residue present in the biosynthetic precursor and the hydroxyglycine derivative dissociates to form the peptide amide and glyoxylic acid [15].
• The channeling of isocitrate through the glyoxylate bypass is regulated via the phosphorylation/dephosphorylation of isocitrate dehydrogenase, the enzyme of the tricarboxylic acid cycle which competes for a common substrate with isocitrate lyase [4].
• The glyoxylate cycle is instrumental in this metabolic process [16].
• Typhi inside macrophages showed increased expression of genes encoding resistance to antimicrobial peptides, used the glyoxylate bypass for fatty acid utilization, and did not induce the SOS response or the oxidative stress response [17].
• The enzymes, which are encoded by different regulons, include members that belong to the tricarboxylic acid cycle, the glyoxylate shunt, the pathway for fatty acid degradation, several dehydrogenases of the flavoprotein class, and the cytochrome o oxidase complex [18].

Anatomical context of oxaldehydic acid

• Mammalian alanine/glyoxylate aminotransferase 1 is imported into peroxisomes via the PTS1 translocation pathway. Increased degeneracy and context specificity of the mammalian PTS1 motif and implications for the peroxisome-to-mitochondrion mistargeting of AGT in primary hyperoxaluria type 1 [19].
• Rough-surfaced membranes were alternatively considered as the subcellular site, but the evidence tends to favor localization of the glyoxylate bypass enzymes in the mitochondria [20].
• During the first 4 or 5 d, glyoxylate cycle enzymes accumulate in microbodies called glyoxysomes [21].
• We have used protein A-gold immunoelectron microscopy to detect two glyoxylate cycle enzymes, isocitrate lyase (ICL) and malate synthase, and two glycolate pathway enzymes, serine:glyoxylate aminotransferase (SGAT) and hydroxypyruvate reductase, in microbodies of transition-stage (day 4) cotyledons [21].
• Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria [22].

Associations of oxaldehydic acid with other chemical compounds

• In addition, mdh3-disrupted cells were unable to grow on oleate whereas growth on other non-fermentable carbon sources was normal, suggesting that MDH3 is involved in the reoxidation of NADH generated during fatty acid beta-oxidation rather than functioning as part of the glyoxylate cycle [23].
• NE uptake activity was measured using [3H]NE, and noradrenergic nerve profiles were visualized by glyoxylic acid (SPG)-induced histofluorescence and tyrosine hydroxylase immunocytochemical staining [24].
• The catalytic activity of tyrosine hydroxylase and of other enzymes required for catecholamine production was demonstrated in the cultures by glyoxylic acid-induced histofluorescence and by radiochemical measurement of the conversion of exogenous tyrosine to norepinephrine [25].
• The expression of some nuclear genes in Saccharomyces cerevisiae, such as the CIT2 gene, which encodes a glyoxylate cycle isoform of citrate synthase, is responsive to the functional state of mitochondria [26].
• Here we report the 1.75A high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively [27].

Gene context of oxaldehydic acid

• We have previously shown that the RTG genes control the retrograde pathway, defined as a change in the expression of a subset of nuclear genes, e.g., the glyoxylate cycle CIT2 gene, in response to changes in the functional state of mitochondria [28].
• Disruption of the chromosomal MDH3 locus produced a reduction in cellular growth rates on acetate, consistent with the presumed function of this isozyme in the glyoxylate pathway of yeast [29].
• We have examined whether other genes of the glyoxylate cycle exhibit retrograde regulation and the role of RTG1 and RTG2 in their expression [30].
• GGT1 and GGT2 are Ala aminotransferase (AlaAT) homologs from Arabidopsis that represent another type of glyoxylate aminotransferase [31].
• The genes for the two unique enzymes of the glyoxylate shunt, aceA and aceB, are located at 90 min on the E. coli K-12 genetic map [32].

Analytical, diagnostic and therapeutic context of oxaldehydic acid

• The circular dichroism spectrum for native aldolase is characteristic of an alpha-helix; incubation of the enzyme with glyoxylate has no effect on this spectrum, but it is considerably altered by pyruvate [33].
• Glyoxysome-like bodies were observed by electron microscopy in fungal structures where the glyoxylate cycle is expected to be active, which is consistent with the presence in both enzyme sequences of motifs associated with glyoxysomal targeting [34].
• Four groups of naive male Sprague-Dawley rats, aged 3, 10, 20, and 28 months. underwent single cell recording for electrophysiological assessment of Purkinje cell firing patterns, followed by perfusion for glyoxylic acid induced catecholamine fluorescence [35].
• The sympathectomy was either verified by (a) glyoxylic acid staining of peripheral blood vessels of the hindpaw or (b) skin temperature measurements of the hindpaws [36].
• 1. Binding of branched-chain 2-oxo acids to defatted bovine serum albumin was shown by gel chromatography and equilibrium dialysis [37].

References