Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.37 (malate dehydrogenase)
4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of methanol oxidation by quinoprotein methanol dehydrogenase (MDH.PQQ) in combination with methanol (MDH.PQQ.methanol) involves Glu-171--CO2(-) general base removal of the hydroxyl proton of methanol in concert with hydride equivalent transfer to the >C5=O quinone carbon of pyrroloquinoline quinone (PQQ) and rearrangement to hydroquinone (PQQH2) with release of formaldehyde. Molecular dynamics (MD) studies of the structures of MDH.PQQ.methanol in the presence of activator NH3 and inhibitor NH4(+) have been carried out. In the MD structure of MDH.PQQ.methanol.NH3, the hydrated NH3 resides at a distance of approximately 24 A away from methanol and the ortho-quinone portion of PQQ. As such, influence of NH3 on the oxidation reaction is not probable. We find that NH4(+) competes with the substrate by hydrogen-bonding to Glu-171CO2(-) such that the MDH.PQQ.methanol.NH4(+) complex is not reactive. Ammonia readily forms imines with quinone. Imines are present in solution as neutral (>C5=NH) and protonated (>C5=NH2(+)) species. MD simulations establish that the >C5=NH2(+) derivative of MDH.PQQ(NH2(+).methanol structure is unreactive because of the nonproductive means of methanol binding. The structure obtained by the MD simulations with the neutral >C5=NH imine of MDH.PQQ(NH).methanol structure is similar to the reactive MDH.PQQ.methanol complex. This active site geometry allows for catalysis of hydride equivalent transfer to the >C5=NH of PQQ(NH) by concerted Glu-171CO(2)(-) general-base removal of the H-OCH3 proton and Arg-324H+ general-acid proton transfer to the imine nitrogen. Enzyme-bound <C5(H)NH2 derivative of PQQ [PQQ(NH)] and CH(2)O product are formed.
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PMID:Mechanisms of ammonia activation and ammonium ion inhibition of quinoprotein methanol dehydrogenase: a computational approach. 1552 Mar 92

Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the mitochondrial malate dehydrogenase gene in the antisense orientation and exhibiting reduced activity of this isoform of malate dehydrogenase show enhanced photosynthetic activity and aerial growth under atmospheric conditions (360 ppm CO2). In comparison to wild-type plants, carbon dioxide assimilation rates and total plant dry matter were up to 11% and 19% enhanced in the transgenics, when assessed on a whole-plant basis. Accumulation of carbohydrates and redox-related compounds such as ascorbate was also markedly elevated in the transgenics. Also increased in the transgenic plants was the capacity to use L-galactono-lactone, the terminal precursor of ascorbate biosynthesis, as a respiratory substrate. Experiments in which ascorbate was fed to isolated leaf discs also resulted in increased rates of photosynthesis providing strong indication for an ascorbate-mediated link between the energy-generating processes of respiration and photosynthesis. This report thus shows that the repression of this mitochondrially localized enzyme improves both carbon assimilation and aerial growth in a crop species.
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PMID:Enhanced photosynthetic performance and growth as a consequence of decreasing mitochondrial malate dehydrogenase activity in transgenic tomato plants. 1566 43

Net photosynthesis (Pn) is reversibly inhibited at moderately high temperature. To investigate this further, we examined the effects of heat stress on Arabidopsis plants in which Rubisco activase or thylakoid membrane fluidity has been modified. During heating leaves from 25 to 40 degrees C at 250 ppm CO2 and 1% O2, the wild-type (WT), plants expressing the 43 kDa isoform only (rwt43), and plants accumulating activase 40% of WT (R100) exhibited similar inhibitions in the Pn and Rubisco activation state. Despite better membrane integrity than WT, plants having less polyunsaturation of thylakoid lipids (fad7/8 double mutant) failed to maintain greater Pn than the WT. Plants expressing the 46 kDa isoform only (rwt46) exhibited the most inhibition, but plants expressing a 46 kDa isoform incapable of redox regulation (C411A) were similar to the WT. The null mutant (rca) exhibited a continuous decline in Pn. As measured by fluorescence, electron transport activity decreased concomitantly with Pn but PSII was not damaged. Following a quick recovery to 25 from 40 degrees C, whereas most lines recovered 90% Pn, the rwt46 and rca lines recovered only to 59 and <10%, respectively. As measured by NADP-malate dehydrogenase activation, after an initial increase at 30 degrees C, stromal oxidation in the WT and rwt46 plants did not increase further as Pn decreased. These results provide additional insight into the role of Rubisco activation and activase in the reversible heat inhibition of Pn.
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PMID:Temperature dependence of photosynthesis in Arabidopsis plants with modifications in Rubisco activase and membrane fluidity. 1569 47

We report a new continuous spectrophotometric assay for human cystathionine beta-synthase (hCBS). This assay relies upon the finding that hCBS will take cysteamine in place of L-homocysteine, thereby producing thialysine. Thialysine is, in turn, decarboxylated by lysine decarboxylase, releasing CO2 that is monitored by the sequential action of phosphoenolpyruvate carboxylase and L-malate dehydrogenase. The decrease in absorbance at 340 nm is monitored as reduced nicotinamide adenine dinucleotide is consumed. Using this four-enzyme couple, we find that Km(app) = 1.2+/-0.2 mM for L-serine and 5.6+/-2.2 mM for cysteamine, with kcat = 1.3+/-0.1s(-1) for the formation of thialysine by hCBS. For comparison purposes, the same hCBS reaction was monitored via a radioactive single time point assay using 14C-(C-1)-labeled L-serine and cysteamine as substrates, counting the thialysine product, following ion exchange chromatography. This assay yielded Km(app) = 2.2+/-0.5 mM for L-serine and 6.6+/-2.2 for cysteamine, with kcat = 2.5+/-0.4 s(-1). These numbers indicate that, although it possesses a shortened carbon chain and lacks a carboxyl group, cysteamine displays a catalytic efficiency (kcat/Km) with hCBS that is within an order of magnitude of that observed with its natural thiol cosubstrate, L-homocysteine.
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PMID:A continuous spectrophotometric assay for human cystathionine beta-synthase. 1595 86

Succinic acid is a four-carbon dicarboxylic acid produced as one of the fermentation products of anaerobic metabolism. Based on the complete genome sequence of a capnophilic succinic acid-producing rumen bacterium, Mannheimia succiniciproducens, gene knockout studies were carried out to understand its anaerobic fermentative metabolism and consequently to develop a metabolically engineered strain capable of producing succinic acid without by-product formation. Among three different CO2-fixing metabolic reactions catalyzed by phosphoenolpyruvate (PEP) carboxykinase, PEP carboxylase, and malic enzyme, PEP carboxykinase was the most important for the anaerobic growth of M. succiniciproducens and succinic acid production. Oxaloacetate formed by carboxylation of PEP was found to be converted to succinic acid by three sequential reactions catalyzed by malate dehydrogenase, fumarase, and fumarate reductase. Major metabolic pathways leading to by-product formation were successfully removed by disrupting the ldhA, pflB, pta, and ackA genes. This metabolically engineered LPK7 strain was able to produce 13.4 g/liter of succinic acid from 20 g/liter glucose with little or no formation of acetic, formic, and lactic acids, resulting in a succinic acid yield of 0.97 mol succinic acid per mol glucose. Fed-batch culture of M. succiniciproducens LPK7 with intermittent glucose feeding allowed the production of 52.4 g/liter of succinic acid, with a succinic acid yield of 1.16 mol succinic acid per mol glucose and a succinic acid productivity of 1.8 g/liter/h, which should be useful for industrial production of succinic acid.
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PMID:Genome-based metabolic engineering of Mannheimia succiniciproducens for succinic acid production. 1651 41

This work is concerned with the metabolism of Caldithrix abyssi-an anaerobic, moderately thermophilic bacterium isolated from deep-sea hydrothermal vents of the Mid-Atlantic Ridge and representing a new, deeply deviated branch within the domain Bacteria. Cells of C. abyssi grown on acetate and nitrate, which was reduced to ammonium, possessed nitrate reductase activity and contained cytochromes of the b and c types. Utilization of acetate occurred as a result of the operation of the TCA and glyoxylate cycles. During growth of C. abyssi on yeast extract, fermentation with the formation of acetate, propionate, hydrogen, and CO2 occurred. In extracts of cells grown on yeast extract, acetate was produced from pyruvate with the involvement of the following enzymes: pyruvate:ferredoxin oxidoreductase (2.6 micromol/(min mg protein)), phosphate acetyltransferase (0.46 micromol/(min mg protein)), and acetate kinase (0.3 micromol/(min mg protein)). The activity of fumarate reductase (0.14 micromol/(min mg protein)), malate dehydrogenase (0.17 micromol/(min mg protein)), and fumarate hydratase (1.2 micromol/(min mg protein)), as well as the presence of cytochrome b, points to the formation of propionate via the methyl-malonyl-CoA pathway. The activity of antioxidant enzymes (catalase and superoxide dismutase) was detected. Thus, enzymatic mechanisms have been elucidated that allow C. abyssi to switch from fermentation to anaerobic respiration and to exist in the gradient of redox conditions characteristic of deep-sea hydrothermal vents.
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PMID:[Investigation of the catabolism of acetate and peptides in the new anaerobic thermophilic bacterium Caldithrix abyssi]. 1675 61

A computer model comprising light reactions, electron-proton transport, enzymatic reactions, and regulatory functions of C3 photosynthesis has been developed as a system of differential budget equations for intermediate compounds. The emphasis is on electron transport through PSII and PSI and on the modeling of Chl fluorescence and 810 nm absorptance signals. Non-photochemical quenching of PSII excitation is controlled by lumenal pH. Alternative electron transport is modeled as the Mehler type O2 reduction plus the malate-oxaloacetate shuttle based on the chloroplast malate dehydrogenase. Carbon reduction enzymes are redox-controlled by the ferredoxin-thioredoxin system, sucrose synthesis is controlled by the fructose 2,6-bisphosphate inhibition of cytosolic FBPase, and starch synthesis is controlled by ADP-glucose pyrophosphorylase. Photorespiratory glycolate pathway is included in an integrated way, sufficient to reproduce steady-state rates of photorespiration. Rate-equations are designed on principles of multisubstrate-multiproduct enzyme kinetics. The parameters of the model were adopted from literature or were estimated from fitting the photosynthetic rate and pool sizes to experimental data. The model provided good simulations for steady-state photosynthesis, Chl fluorescence, and 810 nm transmittance signals under varying light, CO2 and O2 concentrations, as well as for the transients of post-illumination CO2 uptake, Chl fluorescence induction and the 810 nm signal. The modeling shows that the present understanding of photosynthesis incorporated in the model is basically correct, but still insufficient to reproduce the dark-light induction of photosynthesis, the time kinetics of non-photochemical quenching, 'photosynthetic control' of plastoquinone oxidation, cyclic electron flow around PSI, oscillations in photosynthesis. The model may find application for predicting the results of gene transformations, the analysis of kinetic experimental data, the training of students.
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PMID:C3 photosynthesis in silico. 1713 Oct 95

CO2 stimulates the development of many of the intestinal helminths that are able to fix CO2 by means of phosphoenolpyruvate carboxykinase (PEPCK), such as Hysterothylacium aduncum. We determined the activity of CO2-fixing enzymes such as PEPCK and phosphoenolpyruvate carboxylase (PEPC), although no significant activity was detected for pyruvate carboxylase or carboxylating-malic enzyme. The former act on phosphoenolpyruvate (PEP) to yield oxalacetate. In the helminths studied, PEP has a vital role in glucidic metabolism. Consequently, we determined the activity of other enzymes involved in the crossroad of PEP, such as pyruvate kinase (PK), lactate dehydrogenase and malate dehydrogenase. All enzymes detected showed significant variations in activity during the in vitro development of the parasite from the third larval stage to mature adult. Fixing of CO2 by PEPCK decreased during development (from 228 to 115 nmol min(-1) mg(-1) protein), while that by PEPC increased (from 19 to 46 nmol min(-1) mg(-1) protein). This enzyme, which is rare in animals, could play a part in detecting levels of free phosphate, releasing it from PEP when required for processes such as glycogenolysis, glycolysis and adenosine 5'-triphosphate (ATP) synthesis. PK, which showed increasing activity during development up to immature adult (from 56 to 82 nmol min(-1) mg(-1) protein), could act in combination with PEPC to obtain energy in the cytosol (in the form of ATP) and in the mitochondria (possible destination of the pyruvate formed), compensating for the decrease in activity of PEPCK.
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PMID:CO2-fixing enzymes and phosphoenolpyruvate metabolism in the fish parasite Hysterothylacium aduncum (Ascaridoidea, Anisakidae). 1975 Aug 10

Glycine tissue concentrations are increased particularly in nonketotic and ketotic hyperglycinemia, inherited metabolic disorders characterized by severe neurologic damage and brain abnormalities. The present work investigated the in vitro effects of glycine on important parameters of energy metabolism in the brain of young rats. The parameters analyzed were CO2 generated from glucose, acetate and citrate and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, of creatine kinase and Na+,K+-ATPase. Our results show that glycine significantly reduced CO2 production from acetate, but not from glucose and citrate, reflecting an impairment of the citric acid cycle function. We also observed that the activity of the mitochondrial enzyme citrate synthase was markedly inhibited by glycine, whereas the other activities of the citric acid cycle were not altered. Furthermore, the activity of the respiratory chain was reduced at complexes I-III, II-III and II, as well as of the mitochondrial isoform of creatine kinase and Na+,K+-ATPase. The data indicate that glycine severely impairs brain bioenergetics at the level of energy formation, transfer and utilization. Considering the importance of energy metabolism for brain development and functioning, it is presumed that glycine-induced impairment of brain energy homeostasis may be involved at least in part in the neurological damage found in patients affected by disorders in which brain glycine concentrations are increased.
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PMID:Neurochemical evidence that glycine induces bioenergetical dysfunction. 2039 87

Global warming is one of the most serious challenges facing us today. It may be linked to the increase in atmospheric CO2 and other greenhouse gases (GHGs), leading to a rise in sea level, notable shifts in ecosystems, and in the frequency and intensity of wild fires. There is a strong interest in stabilizing the atmospheric concentration of CO2 and other GHGs by decreasing carbon emission and/or increasing carbon sequestration. Biotic sequestration is an important and effective strategy to mitigate the effects of rising atmospheric CO2 concentrations by increasing carbon sequestration and storage capacity of ecosystems using plant photosynthesis and by decreasing carbon emission using biofuel rather than fossil fuel. Improvement of photosynthetic carbon assimilation, using transgenic engineering, potentially provides a set of available and effective tools for enhancing plant carbon sequestration. In this review, firstly different biological methods of CO2 assimilation in C3, C4 and CAM plants are introduced and three types of C4 pathways which have high photosynthetic performance and have evolved as CO2 pumps are briefly summarized. Then (i) the improvement of photosynthetic carbon assimilation of C3 plants by transgenic engineering using non-C4 genes, and (ii) the overexpression of individual or multiple C4 cycle photosynthetic genes (PEPC, PPDK, PCK, NADP-ME and NADP-MDH) in transgenic C3 plants (e.g. tobacco, potato, rice and Arabidopsis) are highlighted. Some transgenic C3 plants (e.g. tobacco, rice and Arabidopsis) overexpressing the FBP/SBPase, ictB and cytochrome c6 genes showed positive effects on photosynthetic efficiency and growth characteristics. However, over the last 28 years, efforts to overexpress individual, double or multiple C4 enzymes in C3 plants like tobacco, potato, rice, and Arabidopsis have produced mixed results that do not confirm or eliminate the possibility of improving photosynthesis of C3 plants by this approach. Finally, a prospect is provided on the challenges of enhancing carbon assimilation of C3 plants using transgenic engineering in the face of global warming, and the trends of the most promising approaches to improving the photosynthetic performance of C3 plants.
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PMID:A critical review on the improvement of photosynthetic carbon assimilation in C3 plants using genetic engineering. 2169 37


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