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:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All the enzymes of the pathway of (S)-alanine fermentation to acetate and propionate were detected in cell-free extracts of Clostridium propionicum . Among these (S)-glutamate dehydrogenase (NAD), (R)-lactate dehydrogenase (NAD) and propionate CoA-transferase were purified to apparent homogeneity. Their structures were presumably alpha 6, alpha 2 and alpha 4, respectively. The latter enzyme was specific for short-chain monocarboxylic acids with a pronounced preference for (R)-lactate over the (S)-enantiomer. The key step of the pathway, the dehydration of (R)-lactate required acetyl phosphate and CoASH under anaerobic conditions. It was inhibited by hydroxylamine, arsenate, azide (1 mM each) or by 0.1 mM 2,4-dinitrophenol. Thus it closely resembled the dehydration of (R)-2-hydroxyglutarate in Acidaminococcus fermentans , although an activation was not necessary.
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PMID:On the dehydration of (R)-lactate in the fermentation of alanine to propionate by Clostridium propionicum. 658 95

Such details of the primary structure were sought that are common in all dehydrogenases of known amino acid sequence. Twenty-six sequences of eight kinds of dehydrogenase (D-glyceraldehyde-3-phosphate dehydrogenase, alcohol dehydrogenase, lactate dehydrogenase, glutamate dehydrogenase, glycerol-3-phosphate dehydrogenase, ribitol dehydrogenase, L-hydroxyacyl-CoA dehydrogenase and homoserine dehydrogenase) have been compared by the aid of the artificial intelligence language Prolog, the amino acids being classified into groups according to their chemical properties, and alpha-helix or beta-sheet-forming abilities. We found tetrapeptides that occurred in all dehydrogenases examined. By using these tetrapeptides as markers a population of 84 partial sequences has been described. The partial sequences constituting this population are peptides comprising 35 residues. It has been shown statistically that these peptides form a homogeneous sample as regards the frequency of occurrence of amino acid groups. This statistically homogeneous partial sequences can be regarded as homologous and it is assumed that their presence is characteristic of dehydrogenases.
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PMID:Homologous partial sequences in dehydrogenases. 667 98

beta-Oxidation of polyunsaturated fatty acids was studied with isolated rat liver mitochondria in state 3 or uncoupled conditions. 1. Incubation of mitochondria with docosahexaenoyl-, linolenoyl- or gamma-linolenoylcarnitine resulted in an increase of the absorbance at 340 minus 385 nm. This increased absorbance was due to an accumulation of beta-oxidation intermediates of the polyunsaturated fatty acids, and not to the reduction of nicotinamide nucleotides. 2. Experiments carried out with soluble fractions of liver mitochondria incubated with docosahexaenoyl-CoA and gamma-linolenoyl-CoA indicated that this ultraviolet light-absorption was at least partly caused by acyl-CoA esters having a 2,4(,7)-di(tri)enoyl-CoA structure. 3. The addition of glutamate to mitochondria oxidizing gamma-linolenoylcarnitine decreased the absorbance at 340 minus 385 nm, and simultaneously stimulated respiration. With liver mitochondria isolated from fasted rats, 6 mM glutamate increased the rate of acetoacetate production from gamma-linolenoylcarnitine by 130 and 210% under state 3 and uncoupled conditions, respectively. Glutamate did not have any significant effect on the degradation of oleoylcarnitine. The proposed explanation for these findings is that the glutamate dehydrogenase reaction can function as a source of NADPH for 2,4-dienoyl-CoA reductase. 4. The degradation of gamma-linolenoylcarnitine to ketone bodies was augmented in mitochondria isolated from rats treated with clofibrate or partially hydrogenated marine oil. 5. We conclude that 2,4-dienoyl-CoA reductase is an important auxiliary enzyme in the beta-oxidation of polyunsaturated fatty acids. Induction of this enzyme by clofibrate or by certain high-fat diets increases mitochondrial capacity for the degradation of polyunsaturated fatty acids.
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PMID:Beta-oxidation of polyunsaturated fatty acids having double bonds at even-numbered positions in isolated rat liver mitochondria. 686 Jun 98

Hyperthermophiles are a recently discovered group of microorganisms that grow at and above 90 degrees C. They currently comprise over 20 different genera, and except for two novel bacteria, all are classified as Archaea. The majority of these organisms are obligately anaerobic heterotrophs that reduce elemental sulfur (S degree) to H2S. The best studied from a biochemical perspective are the archaeon, Pyrococcus furiosus, and the bacterium, Thermotoga maritima, both of which are saccharolytic. P. furiosus is thought to contain a new type of Entner-Doudoroff pathway for the conversion of carbohydrates ultimately to acetate, H2 and CO2. The pathway is independent of nicotinamide nucleotides and involves novel types of ferredoxin-linked oxidoreductases, one of which has tungsten, a rarely used element, as a prosthetic group. The only site of energy conservation is at the level of acetyl CoA, which is the presence of ADP and phosphate is converted to acetate and ATP in a single step. In contrast, T. maritima utilizes a conventional Embden-Meyerhof pathway for sugar oxidation. P. furiosus also utilizes peptides as a sole carbon and energy source. Amino acid oxidation is thought to involve glutamate dehydrogenase together with at least three types of novel ferredoxin-linked oxidoreductases which catalyze the oxidation of 2-ketoglutarate, aryl pyruvates and formaldehyde. One of these enzymes also utilizes tungsten. In P. furiosus, virtually all of the reductant that is generated during the catabolism of both carbohydrates and peptides is channeled to a cytoplasmic hydrogenase. This enzyme is now termed sulhydrogenase, as it reduces both protons to H2 and S degrees (or polysulfide) to H2S. S degrees reduction appears to lead to the conservation of energy in P. furiosus but not in T. maritima, although the mechanism by which this occurs is not known.
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PMID:Biochemical diversity among sulfur-dependent, hyperthermophilic microorganisms. 794 71

Methylmalonate semialdehyde dehydrogenase (MMSDH) is a mitochondrial enzyme which can be acylated by myristoyl-CoA analogs (Deichaite, I., Berthiaume, L., Peseckis, S. M., Patton, W. F., and Resh, M. D. (1993) J. Biol. Chem. 268, 13788-13747). Here we describe the mechanisms which mediate regulation of the enzymatic activity of bovine MMSDH by long chain fatty acylation. The substrate specificity of the acylation reaction was measured in vitro using purified MMSDH and the coenzyme A derivative of an 125I-labeled long chain fatty acid (13-iodotridecanoate), an analog of myristoyl-CoA. Long chain fatty acyl CoAs (> 8 carbons) were able to inhibit radiolabeling of MMSDH. In order to study the physiological role of the acylation process in vivo, a system using highly purified mitochondria from COS-1 cells overexpressing MMSDH was exploited. MMSDH was shown to be processed properly, targeted to the mitochondrial fraction, and enzymatically active. The extent of fatty acylation of MMSDH as well as of other mitochondrial proteins was correlated with the mitochondrial energy level. Biochemical evidence as well as site-specific mutagenesis of cysteine 319 revealed that this highly conserved active site cysteine of MMSDH was the target of the fatty acylation. Another member of the aldehyde dehydrogenase family, yeast aldehyde dehydrogenase was also covalently modified by [125I]13-iodotridecanoyl-CoA and thereby inactivated. Furthermore, we demonstrate that glutamate dehydrogenase, an enzyme that has been previously shown to be strongly inhibited by palmitoyl-CoA, is fatty acylated by the 125I-labeled myristoyl-CoA analog. Our data suggest that attachment of long chain fatty acids to proteins is a new and potentially widespread type of enzyme regulation mechanism that we denote active site fatty acylation.
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PMID:Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins. 812

Pyrococcus furiosus is a strictly anaerobic archaeon that grows optimally at 100 degrees C by a fermentative-type metabolism in which complex peptide mixtures such as yeast extract and Tryptone, and also certain sugars, are oxidized to organic acids, H2 and CO2. Enzymes involved in the utilization of peptides such as proteases, aromatic amino transferases, and glutamate dehydrogenase have been previously purified from this organism. It is shown here that P. furiosus also contains significant cytoplasmic concentrations of a new enzyme termed indolepyruvate ferredoxin oxidoreductase (IOR). This catalyzes the oxidative decarboxylation of aryl pyruvates, which are generated by the transamination of aromatic amino acids, to the corresponding aryl acetyl-CoA. IOR is a tetramer (alpha 2 beta 2) of two identical subunits (66,000 and 23,000 Da) with a molecular weight of 180,000. The enzyme contains one molecule of thiamine pyrophosphate and four [4Fe-4S]2+,1+ and one [3Fe-4S]0,1+ cluster, as determined by iron analyses and EPR spectroscopy. Significant amounts of other metals such as copper and zinc were not detected. IOR was virtually inactive at 25 degrees C and exhibited optimal activity above 90 degrees C (at pH 8.0) and at pH 8.5-10.5 (at 80 degrees C). The enzyme was sensitive to inactivation by O2, losing 50% of its activity after exposure to air for 20 min at 23 degrees C, and was quite thermostable, with a half-life of activity at 80 degrees C (under anaerobic conditions) of about 80 min. The Km values (in microM) for indolepyruvate, p-hydroxyphenylpyruvate, phenylpyruvate, CoASH, and P. furiosus ferredoxin, the physiological electron carrier, were 250, 110, 90, 17, and 48, respectively. IOR was inhibited by KCN (apparent Ki = 7.5 mM), but not by CO (1 atm). An enzyme analogous to IOR has not been reported previously. Curiously, it has few properties in common with the pyruvate ferredoxin oxidoreductase of P. furiosus, even though the two enzymes catalyze virtually identical reactions. In fact, of known ketoacid oxidoreductases, the catalytic mechanism of IOR appears to be most similar to that of the pyruvate ferredoxin oxidoreductase from the hyperthermophilic bacterium Thermotoga maritima.
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PMID:Indolepyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus. A new enzyme involved in peptide fermentation. 820 94

Although heart mitochondria contain glutamate dehydrogenase, it has not been thought to play a role in their metabolism. We investigated this matter to define the conditions under which it is active. We found modest activity in the presence of glutamate and malate and a continuous source of ADP when pyruvate is added. This increases several fold as the osmolarity is increased from 296 to 370 mosM. At the higher osmolarity ammonia formation is brief, associated with a lower intramitochondrial alpha-ketoglutarate from citrate does not make up for the drop in glutamate conversion to alpha-ketoglutarate. Mitochondrial content of nucleotides and CoA compounds are not altered by pyruvate addition. The rate of glutamate deamination by GDH in sonicated heart mitochondria agrees with the rate of ammonia formation in intact mitochondria in the presence of pyruvate (20 nmol/min/mg of mitochondrial protein). We conclude pyruvate lowers mitochondrial oxalacetate which decreases alpha-ketoglutarate formation by transamination. The lower mitochondria alpha-ketoglutarate level permits glutamate deamination until alpha-ketoglutarate reaches a level that inhibits the forward reaction. Further proof of the key role of alpha-ketoglutarate is seen with aminooxyacetate which blocks transamination. In its presence ammonia formation occurs at the same rate (18 nm/min/mg of mitochondrial protein), is not dependent upon pyruvate, and does not stop after a couple of minutes. Leucine, which decreases alpha-ketoglutarate inhibition of GDH, also results in ammonia formation, further supporting the concept of regulation by alpha-ketoglutarate. The higher osmolarity increases GDH activity by increasing alpha-ketoglutarate transport from mitochondria.
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PMID:Conditions for glutamate dehydrogenase activity in heart mitochondria. 837 37

We investigated the substrates for flight in the blister beetle Decapotoma lunata by (a) establishing the patterns of maximum activities of enzymes of various metabolic pathways in the flight muscles, (b) measuring the respiratory rates of flight muscle mitochondria with various substrates and (c) determining metabolite concentrations in flight muscles and haemolymph during a flight period of up to 17 min and over a rest period of up to 2 h following 10 min of flight. Activities of enzymes involved in proline metabolism (glutamate dehydrogenase, alanine aminotransferase, malic enzyme) were much higher in the blister beetle than in the migratory locust Locusta migratoria, whereas the activity of an enzyme responsible for fatty acid oxidation (ss-hydroxyacyl-CoA dehydrogenase) was much lower. Mitochondria from flight muscles of D. lunata have a much higher capacity to oxidise proline than those from L. migratoria. The glycerophosphate shuttle, however, was equally active in both insects. Whereas lipid levels in the haemolymph did not change significantly during flight, there was a continuous decrease in proline levels from 34.8 to 6.6 micromol ml-1 and a simultaneous increase in alanine concentration; carbohydrate levels dropped from 20.1 to 12.2 mg ml-1. In the thorax (flight muscles), glycogen levels were diminished between 2 and 17 min of flight from 25.9 to 6.7 micromol glucose equivalents g-1 fresh mass. Proline concentration dropped continuously from an initial 49.5 to 10.1 micromol g-1 fresh mass, whereas alanine levels rose concomitantly from 2.9 to 17.3 micromol g-1 fresh mass. After termination of a 10 min flight, pre-flight levels of proline in the haemolymph and flight muscles were only re-established after 2 h. In contrast, glycogen levels in the thorax were restored after 1 h. Using the rates of utilisation of substrates during the first 10 min of flight to calculate rates of oxygen consumption during flight, it was shown that overall haemolymph substrates contribute 75 % and those of the flight muscles only 25 %. Although proline is an important substrate for flight in D. lunata, its role is secondary to that of carbohydrates. This type of substrate usage is different from that of the Colorado potato beetle Leptinotarsa decemlineata or the African fruit beetle Pachnoda sinuata, in which carbohydrates are of negligible or only slight importance, respectively.
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PMID:Energy substrates for flight in the blister beetle Decapotoma lunata (Meloidae) 931 22

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.
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PMID:Skeletal muscle oxidative capacity, fiber type, and metabolites after lung transplantation. 1039 Mar 80

The compartmentation of key processes in sugar, organic acid and amino acid metabolism was studied during the development of the flesh and seeds of grape (Vitis vinifera L.) berries. Antibodies specific for enzymes involved in sugar (cell wall and vacuolar invertases, pyrophosphate: fructose 6-phosphate phosphotransferase, aldolase, NADP-glyceraldehyde-P dehydrogenase, cytosolic fructose 1,6-bisphosphatase), photosynthesis (Rubisco, fructose 1,6-bisphosphatase, sedoheptulose 1,7-bisphosphatase), amino acid metabolism (cytosolic and mitochondrial aspartate aminotransferases, alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase), organic acid metabolism (phosphoenolpyruvate carboxylase, NAD- and NADP-dependent malic enzyme, ascorbate peroxidase), and lipid metabolism (acetyl CoA carboxylase, isocitrate lyase) were used to determine how their abundance changed during development. There were marked changes in the abundance of many of these enzymes in both the flesh and seeds. The intercellular location of some enzymes was investigated using immunohistochemistry. Several enzymes (e.g. phosphoenolpyruvate carboxylase and those involved in amino acid metabolism) were associated with tissues likely to function in the transport of imported assimilates, such as the vasculature. Although other enzymes (e.g. NADP-malic enzyme and soluble acid invertase, involved in the metabolism of sugars and organic acids) were largely present in the parenchyma cells of the flesh, their distribution was extremely heterogeneous. This study shows that when considering the metabolism of complex structures such as fruit, it is essential to consider how metabolism is compartmentalized between and within different tissues, even when they are apparently structurally homogeneous.
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PMID:An immunohistochemical study of the compartmentation of metabolism during the development of grape (Vitis vinifera L.) berries. 1093 59


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