Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MALIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources
PubMed1986

Effects of dietary nutrients on lipogenic enzyme and mRNA activities in rat liver during induction.

By feeding a carbohydrate diet (without protein) to fasted rats, malic enzyme mRNA activity in the liver was increased to the level in rats fed a carbohydrate and protein diet, whereas the enzyme activity itself was increased to 60% of that level. It appears that malic enzyme mRNA activity was increased by dietary carbohydrate, while dietary protein contributed to an increase in the translation of mRNA. In the animals fed carbohydrate without protein, glucose-6-phosphate dehydrogenase mRNA activity increased to 50% of the level in rats fed the carbohydrate and protein diet, whereas the enzyme activity increased to only 25%. By feeding a protein diet (without carbohydrate), glucose-6-phosphate dehydrogenase activity increased to 65% of the level in rats fed both carbohydrate and protein. This enzyme induction appears to be more dependent on protein than carbohydrate. With the carbohydrate diet, acetyl-CoA carboxylase was induced up to the level in the carbohydrate and protein diet group, whereas fatty acid synthetase was induced to only 33%. Acetyl-CoA carboxylase induction appears to be carbohydrate dependent. On the other hand, isotopic leucine incorporation studies showed that the magnitudes of the enzyme inductions caused by the dietary nutrients should be ascribed to the enzyme synthesis rates rather than the degradation. By fat feeding, the mRNA activities of malic enzyme and glucose-6-phosphate dehydrogenase were markedly decreased along with the enzyme induction. Fat appears to reduce these enzyme inductions before the translation of mRNA.

Acetyl-CoA Carboxylase↗
PubMed2002

Metabolic network analysis of Bacillus clausii on minimal and semirich medium using (13)C-labeled glucose.

Using (13)C-labeled glucose fed to the facultative alkalophilic Bacillus clausii producing the alkaline serine protease Savinase, the intracellular fluxes were quantified in continuous cultivation and in batch cultivation on a minimal medium. The flux through the pentose phosphate pathway was found to increase with increasing specific growth rate but at a much lower level than previously reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were included in the metabolic network. A substantial flux in the futile cycle involving malic enzyme was estimated, whereas only a very small or zero flux through PEP carboxykinase was estimated, indicating that the latter enzyme was not active during growth on glucose. The uptake of the amino acids in a semirich medium containing 15 of the 20 amino acids normally present in proteins was estimated using fully labeled glucose in batch cultivations. It was found that leucine, isoleucine, and phenylalanine were taken up from the medium and not synthesized de novo from glucose. In contrast, serine and threonine were completely synthesized from other metabolites and not taken up from the medium. Valine, proline, and lysine were partly taken up from the medium and partly synthesized from glucose. The metabolic network analysis was extended to include analysis of growth on the semirich medium containing amino acids, and the metabolic flux distribution on this medium was estimated and compared with growth on minimal medium.

Amino Acids↗
PubMed2006

The Leishmania donovani complex: genotypes of five metabolic enzymes (ICD, ME, MPI, G6PDH, and FH), new targets for multilocus sequence typing.

Flagellates of the Leishmania donovani complex are causative agents of human cutaneous and visceral leishmaniasis. The complex is comprised of L. donovani, Leishmania infantum and Leishmania archibaldi, although the latter is not now considered to be a valid species. Morphological distinction of Leishmania species is impractical, so biochemical, immunological and DNA-based criteria were introduced. Multilocus enzyme electrophoresis (MLEE) is the present gold standard. We have sequenced the genes encoding five metabolic enzymes used for MLEE, both to resolve the DNA diversity underlying isoenzyme mobility differences and to explore the potential of these targets for higher resolution PCR-based multilocus sequence typing. The genes sequenced were isocitrate dehydrogenase, malic enzyme, mannose phosphate isomerase, glucose-6-phosphate dehydrogenase, and fumarate hydratase, for 17 strains of L. infantum, seven strains of L. donovani, and three strains of L. archibaldi. Protein mobilities predicted from amino acid sequences did not always accord precisely with reported MLEE profiles. A high number of heterozygous sites was detected. Heterozygosity was particularly frequent in some strains and indirectly supported the presence of genetic exchange in Leishmania. Phylogenetic analysis of a concatenated alignment based on a total of 263 kb protein-coding sequences showed strong correlation of genotype with geographical origin. Europe and Africa appear to represent independent evolutionary centres.

Animals↗
PubMed1979

Studies on regulatory functions of malic enzymes. VII. Structural and functional characteristics of sulfhydryl groups in NADP-linked malic enzyme from Escherichia coli W.

NADP-linked malic enzyme from Escherichia coli W contains 7 cysteinyl residues per enzyme subunit. The reactivity of sulfhydryl (SH) groups of the enzyme was examined using several SH reagents, including 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and N-ethylmaleimide (NEM). 1. Two SH groups in the native enzyme subunit reacted with DTNB (or NEM) with different reaction rates, accompanied by a complete loss of the enzyme activity. The second-order modification rate constant of the "fast SH group" with DTNB coincided with the second-order inactivation rate constant of the enzyme by the reagent, suggesting that modification of the "fast SH group" is responsible for the inactivation. When the enzyme was denatured in 4 M guanidine HCl, all the SH groups reacted with the two reagents. 2. Althoug the inactivation rate constant was increased by the addition of Mg2+, an essential cofactor in the enzyme reaction, the modification rate constant of the "fast SH group" was unaffected. The relationship between the number of SH groups modified with DTNB or NEM and the residual enzyme activity in the absence of Mg2+ was linear, whereas that in the presence of Mg2+ was concave-upwards. These results suggest that the Mg2+-dependent increase in the inactivation rate constant is not the result of an increase in the rate constant of the "fast FH group" modification. 3. The absorption spectrum of the enzyme in the ultraviolet region was changed by addition of Mg2+. The dissociation constant of the Mg2+-enzyme complex obtained from the Mg2+- dependent increment of the difference absorption coincided with that obtained from the Mg2+- dependent enhancement of NEM inactivation. 4. Both the inactivation rate constant and the modification rate constant of the "fast SH group" were decreased by the addition of NADP+. The protective effect of NADP+ was increased by the addition of Mg2+. Based on the above results, the effects of Mg2+ on the SH-group modification are discussed from the viewpoint of conformational alteration of the enzyme.

Cysteine↗
PubMed1989

Phosphate Starvation Inducible ;Bypasses' of Adenylate and Phosphate Dependent Glycolytic Enzymes in Brassica nigra Suspension Cells.

When Brassica nigra leaf petiole suspension cells were subjected to 7 days of inorganic phosphate (Pi) starvation the extractable activity of: (a) pyrophosphate:fructose 6-phosphate 1-phosphotransferase, nonphosphorylating NADP-glyceraldehyde 3-phosphate dehydrogenase, phosphoenolpyruvate phosphatase, and phosphoenolpyruvate carboxylase increased at least fivefold, (b) phosphorylating NAD-glyceraldehyde 3-phosphate dehydrogenase decreased about sixfold, and (c) ATP:fructose 6-phosphate 1-phosphotransferase, 3-phosphoglycerate kinase, pyruvate kinase, or NAD malic enzyme was not altered. Pi deprivation also resulted in significant reductions in extractable levels of Pi, ATP, ADP, fructose 2,6-bisphosphate, and soluble protein, but caused a sixfold elevation in free amino acid concentrations. No change in inorganic pyrophosphate concentration was observed following Pi starvation. It is hypothesized that pyrophosphate:fructose 6-phosphate 1-phosphotransferase, nonphosphorylating NADP-glyceraldehyde 3-phosphate dehydrogenase, and phosphoenolpyruvate phosphatase bypass nucleotide phosphate or Pi-dependent glycolytic reactions during sustained periods of Pi depletion.

Journal Article↗
PubMed1992

Cloning and sequence analysis of cDNA encoding aspartate aminotransferase isozymes from Panicum miliaceum L., a C4 plant.

The cytosolic and mitochondrial isozymes of aspartate aminotransferase (AspAT) function in the C4 dicarboxylate cycle of photosynthesis. We constructed a cDNA library from leaf tissues of Panicum miliaceum, an NAD-malic-enzyme-type C4 plant and screened the library for AspAT isozymes. A full-length cDNA clone for cytosolic AspAT was isolated. This clone contains an open reading frame that encodes 409 amino acids. We also isolated two cDNA clones for different precursors of mitochondrial AspAT. Comparing these two sequences in the coding regions, we found 12 amino acid substitutions out of 28 base substitutions. The encoded amino acid sequences predict that mitochondrial AspAT are synthesized as precursor proteins of 428 amino acid residues, which each consist of a mature enzyme of 400 amino acid residues and a 28-amino-acid presequence. This prediction coincides with the observation that the in vitro translation product of the mRNA for mitochondrial AspAT was substantially larger than the mature form. A comparison of the amino acid sequences of the AspAT isozymes from P. miliaceum with the published sequences for the enzymes from various animals and microorganisms reveals that functionally and/or structurally important residues are almost entirely conserved in all AspAT species.

Amino Acid Sequence↗
PubMed1995

Pleotropic effects of dietary DHEA.

We present data pertaining to some of the in vivo effects associated with dietary DHEA administration to mice and rats. Dietary DHEA leads to: (1) decrease in body weight gain; (2) relative increases in liver weight; (3) liver color change; (4) induction of hepatic peroxisomal enzymes; (5) proliferation of hepatic peroxisomes with increased cross-sectional area; (6) decreased hepatic mitochondrial cross-sectional area; (7) elevated levels of hepatic cytosolic malic enzyme; (8) slight decreases, significant decreases, or significant increases in serum triglyceride levels, depending on mouse strain; (9) increases in total serum cholesterol levels; (10) significant decreases in the hepatic rates of fatty acid synthesis; (11) significant increases in the hepatic rates of cholesterol synthesis; (12) decreases in both protein content and specific activity of hepatic mitochondrial carbamoyl phosphate synthetase-I without concomitant changes in serum urea nitrogen; (13) induction of glutathione S-transferase activity in liver; (14) decrease in hepatic endogenous protein phosphorylation; (15) increase in hepatic AMPase and GTPase activities; (16) formation of 5-androstene-3 beta,17 beta-diol as a major metabolite of DHEA by subcellular fractions of liver, which is reflected in serum and tissue levels; and (17) reduction in serum prolactin levels.

Animals↗
PubMed1988

Free fatty acid inhibition of the insulin induction of glucose-6-phosphate dehydrogenase in rat hepatocyte monolayers.

Rat hepatocytes in monolayer culture were utilized to determine if the decrease in glucose-6-phosphate dehydrogenase (G6PD) activity resulting from the ingestion of fat can be mimicked by the addition of fatty acids to a chemically, hormonally defined medium. G6PD activity in cultured hepatocytes was induced several-fold by insulin. Dexamethasone or T3 did not amplify the insulin induction of G6PD. Glucose alone increased G6PD activity in cultured hepatocytes from fasted donors by nearly 500%. Insulin in combination with glucose induced G6PD an additional two-fold. The increase in G6PD activity caused by glucose was greater in hepatocytes isolated from 72 hr-fasted rats as compared to fed donor rats. Such a response was reminiscent of the "overshoot" phenomenon in which G6PD activity is induced well above the normal level by fasting-refeeding rats a high glucose diet. Addition of linoleate to the medium resulted in a significant suppression of insulin's ability to induce G6PD, but linoleate had no effect on the induction of G6PD activity by glucose alone. A shift to the right in the insulin-response curve for the induction of G6PD also was detected for the induction of malic enzyme and acetyl-CoA carboxylase. Arachidonate (0.25 mM) was a significantly more effective inhibitor of the insulin action than linoleate was. Apparently rat hepatocytes in monolayer culture can be utilized as a model to investigate the molecular mechanism by which fatty acids inhibit the production of lipogenic enzymes. In part, this mechanism of fatty acid inhibition involves desensitization of hepatocytes to the lipogenic action of insulin.

Acetyl-CoA Carboxylase↗
PubMed1975

Enzymatic changes in lung tissue of asbestotic guinea pigs.

The changes in the activities of some mitochondrial and soluble enzymes in the lungs of guinea pig, caused by three varieties of asbestos dust 120 days after intratracheal injection, were studied. Marked increase was observed in mitochondrial cytochrome oxidase, diaphorase and malic dehydrogenase. Among the soluble enzymes, lactic dehydrogenase showed the maximum variation.

Acid Phosphatase↗
PubMed1984

The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme.

Little evidence has been available on the oxidative pathways of glutamine and glutamate, the major respiratory substrates of cancer cells. Glutamate formed from glutamine by phosphate-dependent glutaminase undergoes quantitative transamination by aerobic tumor mitochondria to yield aspartate. However, when malate is also added there is a pronounced decrease in aspartate production and a large formation of citrate and alanine, in both state 3 and 4 conditions. In contrast, addition of malate to normal rat heart, liver, or kidney mitochondria oxidizing glutamate causes a marked increase in aspartate production. Further analysis showed that extramitochondrial malate is oxidized almost quantitatively to pyruvate + CO2 by NAD(P)+-linked malic enzyme, present in the mitochondria of all tumors tested, but absent in heart, liver, and kidney mitochondria. On the other hand intramitochondrial malate generated from glutamate is oxidized quantitatively to oxalacetate by mitochondrial malate dehydrogenase of tumors. Acetyl-CoA derived from extramitochondrial malate via pyruvate and oxalacetate derived from glutamate via intramitochondrial malate are quantitatively converted into citrate, which is extruded. No evidence was found that malic enzyme of tumor mitochondria converts glutamate-derived malate into pyruvate as postulated in other reports. Possible mechanisms for the integration of mitochondrial malic enzyme and malate dehydrogenase activities in tumors are discussed.

Animals↗
PubMed1999

Peroxisome-proliferator regulates key enzymes of the tryptophan-NAD+ pathway.

Structually diverse peroxisome-proliferators (PPs) were investigated regarding their effects on NAD+ level and two key enzyme activities in the tryptophan (Trp)-NAD+ pathway in the liver of rats (Sprague-Dawley male) fed PP-containing diets freely for 2 weeks. All PPs, except for thyroxine, significantly increased hepatic NAD+ level in concert with hepatic hypertrophy. Activity of quinolinate phosphoribosyltransferase (QAPRTase), one of the key enzymes in the Trp-NAD+ pathway, was increased by the PPs which caused significant increase in the hepatic NAD+. On the other hand, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSDase), another key enzyme in the Trp-NAD+ pathway, was drastically inhibited by all PPs except for linolenic acid, which was only slightly inhibitory. Most PPs investigated activated peroxisomal marker enzymes such as palmitoyl-CoA oxidase, catalase, and PPAR-alpha(peroxisome-proliferator activated receptor-alpha)-dependent enzymes, such as malic enzyme and l-3-glycerophosphate dehydrogenase. NAD+ was also increased in the rat hepatocytes cultured in the medium supplemented with PPs. These data suggested that regulation of the key enzymes in the Trp-NAD+ pathway was associated with PPAR-alpha directly or indirectly, and as a consequence the hepatic NAD+ was increased by PPs.

Animals↗
PubMed1980

Deuterium isotope effects on lactate dehydrogenase using L-2-hydroxysuccinamate and effect of an inhibitor in the variable substrate on observed isotope effects.

L-2-Hydroxysuccinamate, the 4-amide analogue of L-malate, is a substrate for beef heart lactate dehydrogenase with values for V and V/K at pH 8 which are 0.01 and 0.0002% of the corresponding constants for L-lactate and an equilibrium constant of 2.19 X 10(-13) M. Similar values are observed for rabbit muscle lactate dehydrogenase. With beef heart lactate dehydrogenase, the pH-independent isotope effects on V and V/K of 3.7 +/- 0.5 and 3.3 +/- 0.4 indicate that hydride transfer is largely rate limiting for this reaction. L-2-Hydroxysuccinamate undergoes hydrolysis in mildly acidic or basic solution, and the pH vs. rate profile suggests intramolecular catalysis by the undissociated 1-carboxyl group in the pH range 1.5--3.5. The substrate activity of L-2-hydroxysuccinamate with pigeon liver malic enzyme reported by M. I. Schimerlik & W. W. Cleland [(1977) Biochemistry 16, 565] was caused by contaminating L-malate; the purified compound shows no activity (<0.015%). Theory has been developed for the effect on V and V/K deuterium isotope effects of having an inhibitor present in the variable substrate and tested by adding trifluoroethanol to deuterated or unlabeled cyclohexanol as substrates for alcohol dehydrogenase.

Amides↗
PubMed1973

Photosynthetic carbon metabolism in isolated maize bundle sheath strands.

Photosynthetically active bundle sheath strands capable of assimilating up to 8 micromoles CO(2) per milligram chlorophyll per hour have been isolated from fully expanded leaves of Zea mays L. Mesophyll cell contamination of the preparations was negligible, as evidenced by light and electron microscopy and by a high ratio of chlorophyll a to chlorophyll b in the strands. Ribose 5-phosphate markedly stimulated the rate of photosynthetic (14)CO(2) fixation by the isolated strands. In contrast, both pyruvate and phosphoenolpyruvate had a comparatively small stimulatory effect on bundle sheath (14)CO(2) fixation. After 5 minutes of photosynthesis in (14)C-bicarbonate, 95% of the incorporated (14)C was found in compounds other than C(4)-dicarboxylic acids, most notably in 3-phosphoglycerate and sugar phosphates. A similar distribution of (14)C was observed in the presence of exogenous ribose 5-phosphate. Extracts of bundle sheath strands contained high specific activities of "malic" enzyme, phosphoglycolate phosphatase, hydroxypyruvate reductase, and ribulose 1,5-diphosphate carboxylase, whereas the specific activities of NADP(+)-malate dehydrogenase and phosphopyruvate carboxylase were extremely low. These results indicate that the Calvin cycle occurs in the bundle sheath cells of maize.

Journal Article↗
PubMed1996

Growth Rate-Dependent Modulation of Carbon Flux through Central Metabolism and the Kinetic Consequences for Glucose-Limited Chemostat Cultures of Corynebacterium glutamicum.

The physiological behavior of Corynebacterium glutamicum in glucose-limited chemostat cultures was examined from both growth kinetics and enzymatic viewpoints. Metabolic fluxes within the central metabolism were calculated from growth kinetics and analyzed in relation to specific enzyme activities. At high growth rates, incomplete glucose removal was observed, and this was attributed to rate-limiting capacity of the phosphotransferase system transporter and the probable contribution of a low-affinity permease uptake mechanism. The improved biomass yield observed at high growth rates was related to a shift in the profile of anaplerotic carboxylation reactions, with pyruvate carboxylase replacing malic enzyme. Phosphoenolpyruvate carboxylase, an activity often assumed to be the major anaplerotic reaction during growth of C. glutamicum on glucose, was present at only low levels and is unlikely to contribute significantly to tricarboxylic acid cycle fuelling other than at low growth rates.

Journal Article↗
PubMed1991

Isoelectrofocusing of rat muscle adenylosuccinase.

Adenylosuccinase catalyses the conversion of adenylosuccinic acid to AMP and fumarate. We have developed a coupled enzyme staining procedure applicable to nitrocellulose blots after agarose gel isoelectrofocusing of rat muscle adenylosuccinase. The coupling enzymes, fumarase (fumarate to L-malate) and malic enzyme (L-malate to pyruvate and NADPH), are adsorbed to nitrocellulose prior to blotting. The NADPH, mediated by phenazine methosulfate, converts a tetrazolium salt to its blue formazan. This procedure demonstrated that rat muscle adenylosuccinase consists of three isomeric forms present in similar amounts.

Adenosine Monophosphate↗
PubMed2005

The effect of phytic acid on the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism.

In this study, six groups of rats were fed as follows: Groups 1 and 2 were fed formulated diets supplemented with zinc or without zinc respectively. Groups 3 and 4 were fed formulated diets supplemented with zinc plus phytic acid extracted from sweet potato (Ipomea batatas) or commercial phytic acid respectively. Groups 5 and 6 were fed formulated diets supplemented with phytic acid extract from sweet potato or commercial phytic acid respectively. The animals were fed for three weeks and then sacrificed The activities of key enzymes of carbohydrate and lipid metabolism as well as transaminases in the liver were determined. Blood glucose level was also assessed. Phytic acid extract consumption from sweet potato and commercial phytic acid plus zinc supplement lowered blood glucose levels. There was no significant change in the activity of 6-phosphogluconate dehydrogenase among the groups. Similarly, phytic acid supplementation showed no significant decrease in the activity of pyruvate kinase compared to the group fed formulated diets. There was a significant increase in the activity of glucose-6-phosphate dehydrogenase in the groups fed phytic extract from sweet potato compared to the other groups. The activities of malic enzyme and ATP-citrate lyase in this study were not significantly altered among the groups. There is a lowering of blood glucose levels which is desirable for diabetics who consume sweet potato diets. The changes in some of the hepatic metabolic enzymes are geared towards compensating for the decreased glycolytic responses.

Animal Feed↗
PubMed1996

Effect of hepatocyte growth factor/scatter factor on lipogenesis in adult rat hepatocytes in primary culture.

Hepatocyte growth factor (HGF)/scatter factor is known to be the most potent mitogen for hepatocytes. In this paper, we report that lipogenesis in primary cultured rat hepatocytes treated with 10 ng/ml of recombinant human HGF (rhHGF) for 24 h was stimulated, as measured by the incorporation of 3H2O into long-chain fatty acids, to more than twice as much as the control. Insulin (0.1 microM) was more effective than rhHGF but rhHGF did not show an additive or synergistic effect when added to insulin. We also showed that treatment with rhHGF increased the activities of glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme, key enzymes which supply NADPH for lipogenesis, and acetyl-CoA carboxylase, the rate-limiting enzyme of lipogenesis. The increase in G6PDH and acetyl-CoA carboxylase activities was accompanied by increases in the levels of mRNA for the enzymes. These results suggest that HGF is involved in liver regeneration not only by stimulation of cell proliferation but also by acceleration of differentiation of hepatocytes.

Acetyl-CoA Carboxylase↗
PubMed2001

Central carbon metabolism of Saccharomyces cerevisiae explored by biosynthetic fractional (13)C labeling of common amino acids.

Aerobic and anaerobic central metabolism of Saccharomyces cerevisiae cells was explored in batch cultures on a minimal medium containing glucose as the sole carbon source, using biosynthetic fractional (13)C labeling of proteinogenic amino acids. This allowed, firstly, unravelling of the network of active central pathways in cytosol and mitochondria, secondly, determination of flux ratios characterizing glycolysis, pentose phosphate cycle, tricarboxylic acid cycle and C1-metabolism, and thirdly, assessment of intercompartmental transport fluxes of pyruvate, acetyl-CoA, oxaloacetate and glycine. The data also revealed that alanine aminotransferase is located in the mitochondria, and that amino acids are synthesized according to documented pathways. In both the aerobic and the anaerobic regime: (a) the mitochondrial glycine cleavage pathway is active, and efflux of glycine into the cytosol is observed; (b) the pentose phosphate pathways serve for biosynthesis only, i.e. phosphoenolpyruvate is entirely generated via glycolysis; (c) the majority of the cytosolic oxaloacetate is synthesized via anaplerotic carboxylation of pyruvate; (d) the malic enzyme plays a key role for mitochondrial pyruvate metabolism; (e) the transfer of oxaloacetate from the cytosol to the mitochondria is largely unidirectional, and the activity of the malate-aspartate shuttle and the succinate-fumarate carrier is low; (e) a large fraction of the mitochondrial pyruvate is imported from the cytosol; and (f) the glyoxylate cycle is inactive. In the aerobic regime, 75% of mitochondrial oxaloacetate arises from anaplerotic carboxylation of pyruvate, while in the anaerobic regime, the tricarboxylic acid cycle is operating in a branched fashion to fulfill biosynthetic demands only. The present study shows that fractional (13)C labeling of amino acids represents a powerful approach to study compartmented eukaryotic systems.

Acetyl Coenzyme A↗