Disease relevance of Aepfelsaeure

• Linkage group V of platyfishes and Swordtails of the genus Xiphophorus (Poeciliidae): linkage of loci for malate dehydrogenase-2 and esterase-1 and esterase-4 with a gene controlling the severity of hybrid melanomas [1].
• We have introduced efficient pathways for malate degradation in S. cerevisiae by cloning and expressing the Schizosaccharomyces pombe malate permease (mae1) gene with either the S. pombe malic enzyme (mae2) or Lactococcus lactis malolactic (mleS) gene in this yeast [2].
• Two kaempferol glycosides remained largely unaffected, and sinapoyl malate decreased strongly upon bacterial infection with a time course inversely correlated with that of the accumulating tryptophan-related products [3].
• Like other sHSPs, recombinant Synechocystis HSP17 formed stable complexes with denatured malate dehydrogenase and served as a reservoir for the unfolded substrate, transferring it to the DnaK/DnaJ/GrpE and GroEL/ES chaperone network for subsequent refolding [4].
• Thus, strains of Lactobacillus casei and enterococci readily grow at the expense of substrates such as gluconate, malate and pentitols [5].

Psychiatry related information on Aepfelsaeure

• Greater initial positive cooperative behavior between malate binding sites is observed with Mg2+ as cation [6].
• Particularly in Alzheimer's disease, the activity of malate dehydrogenase was markedly increased [7].
• The water-soluble proteins of the cerebral gray matter and some enzyme systems (cholinesterase, acetylcholinesterase, lactate dehydrogenase, malate dehydrogenase, acid phosphatase) were studied in 9 autopsy cases of Alzheimer's presenile or senile dementia, 1 case of Pick's disease and 1 case of cerebral arteriosclerosis [7].

High impact information on Aepfelsaeure

• In Part II, the conclusions are used in the design and synthesis of two modified forms of the enzyme; one in which the substrate specificity is shifted to produce a more effective malate dehydrogenase than that isolated from the host organism and one which no longer requires its allosteric activator (fructose 1,6-bisphosphate) [8].
• Similarly, the activity of liver acetyl CoA carboxylase, fatty acid synthetase, citrate cleavage enzyme, malate dehydrogenase, and glucose-6-phosphate dehydrogenase was diminished in U [9].
• Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria [10].
• State III (activated) mitochondrial respiration rates with pyruvate/malate, glutamate/malate, and succinate as substrates were assayed in isolated intact skeletal muscle mitochondria in 29 subjects aged 16-92 years [11].
• These results show that the aspartate/glutamate carrier is regulated by Ca(2+) through a mechanism independent of Ca(2+) entry into mitochondria, and suggest a novel mechanism of Ca(2+) regulation of the aspartate/malate shuttle [12].

Chemical compound and disease context of Aepfelsaeure

• Mitochondrial malic enzymes. Mitochondrial NAD(P)+-dependent malic enzyme activity and malate-dependent pyruvate formation are progression-linked in Morris hepatomas [13].
• YheL conferred Na(+) uptake capacity on everted membrane vesicles from an antiporter-deficient E. coli mutant that was consistent with a secondary Na(+)/H(+) antiport, but YqkI-dependent Na(+) uptake depended on intravesicular malate and extravesicular lactate [14].
• Membrane potential-generating transport of citrate and malate catalyzed by CitP of Leuconostoc mesenteroides [15].
• Malate dehydrogenase from Escherichia coli is highly specific for the oxidation of malate to oxaloacetate [16].
• A periplasmic binding protein essential for high-affinity transport of the C4-dicarboxylates malate, succinate and fumarate across the cytoplasmic membrane of the purple photosynthetic bacterium Rhodobacter capsulatus has been purified to homogeneity and some of its ligand-binding properties characterized [17].

Biological context of Aepfelsaeure

• The binding site for shifting the gate is, however, located on the extracellular face of the channel since cytoplasmic malate proved ineffective [18].
• In this pathway, two specific enzymes, isocitrate lyase and malate synthase, are activated to divert isocitrate from the tricarboxylic acid cycle and prevent the quantitative loss of acetate carbons as carbon dioxide [19].
• The genome lacks recognizable genes for 6-phosphofructokinase, an essential enzyme in the Embden-Meyerhof-Parnas pathway, and for two enzymes in the tricarboxylic acid cycle, the 2-oxoglutarate dehydrogenase complex and malate dehydrogenase, so glucose can be metabolized only by the Entner-Doudoroff pathway [20].
• The genes coding for malate synthase, isocitrate lyase, and isocitrate dehydrogenase kinase/phosphatase are located in the same operon [19].
• The data are consistent with carboxylation by a cytosolic PEPCK providing a C4 acid, such as malate, to the chloroplast for decarboxylation to elevate the CO2 concentration at the Rubisco fixation site [21].

Anatomical context of Aepfelsaeure

• Malate-induced feedback regulation of plasma membrane anion channels could provide a CO2 sensor to guard cells [18].
• Superfusion of guard cell protoplasts with malate solutions in the physiological range caused the voltage-gate to shift towards hyperpolarized potentials (Km(mal) = 0.4 mM elicits a 38 mV shift) [18].
• The midpoint redox potential of -315 mV places 2-Cys Prx reduction after Calvin cycle activation and before switching the malate valve for export of excess reduction equivalents to the cytosol [22].
• To fulfil many of these roles, malate has to be accumulated within the large central vacuole [23].
• Physiological analysis of a transferred DNA knockout mutant for AtALMT1 as well as electrophysiological examination of the protein expressed in Xenopus oocytes showed that AtALMT1 is critical for Arabidopsis Al tolerance and encodes the Al-activated root malate efflux transporter associated with tolerance [24].

Associations of Aepfelsaeure with other chemical compounds

• The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP-dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%) [25].
• Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase [26].
• Based on this information, a database search led to the identification of a gene encoding a human hypothetical protein homologous to bacterial FAD-dependent malate dehydrogenases and targeted to mitochondria [27].
• At a low CO2/high O2 ratio that inhibits the carboxylase activity of Rubisco, much malate accumulates, which suggests that the oxygen-insensitive phosphoenolpyruvate carboxylase becomes a significant component of the lower CO2 fixation rate [28].
• Vacuoles isolated from Arabidopsis WT leaves exhibited carbonylcyanide m-chlorophenylhydrazone and citrate inhibitable malate transport, which was not stimulated by sodium [23].

Gene context of Aepfelsaeure

• In the absence of Yfh1p, activity of Fe-S-containing enzymes (aconitase, succinate dehydrogenase) is decreased, whereas the activity of a non-Fe-S-containing enzyme (malate dehydrogenase) is unaffected [29].
• The nucleotide sequence corresponding to codons for the 17-amino acid residues in the presumed targeting presequence for yeast mitochondrial malate dehydrogenase was removed by oligonucleotide-directed mutagenesis of the isolated gene (MDH1) [30].
• Glucose-induced degradation of the MDH2 isozyme of malate dehydrogenase in yeast [31].
• We observed that inhibition of malate transport by Slc25a10 suppression significantly reduced the citrate transport from the mitochondria to the cytosol [32].
• The purpose of this work is to extend our understanding of these elements and their roles to inducible allantoin pathway genes using the DAL7 (encoding malate synthase) as a model [33].

Analytical, diagnostic and therapeutic context of Aepfelsaeure

• We suggest that stomata sense changes in the intercellular CO2 concentration and thus the photosynthetic activity of the mesophyll via feedback regulation of anion efflux from guard cells through malate-sensitive GCAC1 [18].
• The amino acids for substrate and cofactor binding identified by x-ray crystallography for pig heart cytoplasmic malate dehydrogenase are conserved in the 319-amino-acid-long mature plant enzyme [34].
• The result confirms the stereochemistry of the malate/succinate transformation, as well as the NAD+/NADH interconversion, and demonstrates the usefulness of the single-crystal neutron diffraction method for determining the absolute configuration of molecules having a chiral monodeuteriomethylene group [35].
• Malate thiokinase has been purified to apparent homogeneity by employing conventional purification techniques along with affinity chromatography [36].
• When fluorescence titrations were used to monitor the ability of cytoplasmic malate dehydrogenase to form a binary complex with NADH and to form a ternary complex with NADH and hydroxymalonate, only the formation of ternary complex seemed to be effected by arginine modification [37].

References