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)

Binding experiments indicate that mitochondrial aspartate aminotransferase can associate with the alpha-ketoglutarate dehydrogenase complex and that mitochondrial malate dehydrogenase can associate with this binary complex to form a ternary complex. Formation of this ternary complex enables low levels of the alpha-ketoglutarate dehydrogenase complex, in the presence of the aminotransferase, to reverse inhibition of malate oxidation by glutamate. Thus, glutamate can react with the aminotransferase in this complex without glutamate inhibiting production of oxalacetate by the malate dehydrogenase in the complex. The conversion of glutamate to alpha-ketoglutarate could also be facilitated because in the trienzyme complex, oxalacetate might be directly transferred from malate dehydrogenase to the aminotransferase. In addition, association of malate dehydrogenase with these other two enzymes enhances malate dehydrogenase activity due to a marked decrease in the Km of malate. The potential ability of the aminotransferase to transfer directly alpha-ketoglutarate to the alpha-ketoglutarate dehydrogenase complex in this multienzyme system plus the ability of succinyl-CoA, a product of this transfer, to inhibit citrate synthase could play a role in preventing alpha-ketoglutarate and citrate from accumulating in high levels. This would maintain the catalytic activity of the multienzyme system because alpha-ketoglutarate and citrate allosterically inhibit malate dehydrogenase and dissociate this enzyme from the multienzyme system. In addition, citrate also competitively inhibits fumarase. Consequently, when the levels of alpha-ketoglutarate and citrate are high and the multienzyme system is not required to convert glutamate to alpha-ketoglutarate, it is inactive. However, control by citrate would be expected to be absent in rapidly dividing tumors which characteristically have low mitochondrial levels of citrate.
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PMID:Regulation of malate dehydrogenase activity by glutamate, citrate, alpha-ketoglutarate, and multienzyme interaction. 289 80

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p less than 0.05), 0.52 (p less than 0.01), and 0.55 (p less than 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 less than or equal to r less than or equal to 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25-50% of the total phenotypic variation when data are adjusted for age and sex differences.
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PMID:Genetic effects in human skeletal muscle fiber type distribution and enzyme activities. 294 86

Twenty-three male Black African and 23 male Caucasian subjects, ascertained as sedentary, participated in this study designed to determine whether there were differences in skeletal muscle histochemical and biochemical characteristics between racial groups. Muscle fiber type proportions (I, IIa, and IIb), fiber areas and activities of several enzyme markers of different energy metabolic pathways were determined from a biopsy of the vastus lateralis. Results indicated that Caucasians had a higher percent type I (8%, P less than 0.01) and a lower percent type IIa (6.7%, P less than 0.05) fiber proportions than Africans. No significant differences were observed between the two racial groups in the type IIb fiber proportion or in the three fiber type areas. Enzymes catalyzing reactions in phosphagenic [creatine kinase (CK)] and glycolytic [hexokinase (HK), phosphofructokinase (PFK), and lactate dehydrogenase (LDH)] metabolic pathways had significantly higher activities (about 30-40%) in the Black African group than in the Caucasian group (P less than 0.01). No significant difference was noted in the activities of oxidative enzymes [malate dehydrogenase (MDH), oxoglutarate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA dehydrogenase (HADH)]. Consequently, the PFK/OGDH ratio was significantly elevated in Africans (P less than 0.05). The racial differences observed between Africans and Caucasians in fiber type proportion and enzyme activities of the phosphagenic and glycolytic metabolic pathways may well result from inherited variation. These data suggest that sedentary male Black individuals are, in terms of skeletal muscle characteristics, well endowed for sport events of short duration.
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PMID:Skeletal muscle characteristics in sedentary black and Caucasian males. 294 52

Sedentary subjects were submitted to repeated concentric isokinetic strength training protocols separated by a 50-day detraining period. Peak torque output of the quadriceps muscle group increased by 54% after the first ten-week training protocol. No significant changes in mean skeletal muscle fiber area were observed while a significant increase in percent fiber type and percent fiber area was noticed for type IIa fibers. The activities of the enzymes hexokinase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase were also increased significantly. Fifty days without training induced a significant decline in peak torque output. All the enzymes that responded to the first training protocol maintained their elevated activities over the detraining period except for the enzyme oxoglutarate dehydrogenase. A second training protocol administered to the same subjects following the 50-day inactivity period did not result in any significant increase in maximum torque output and fiber area. It is concluded that the isokinetic strength training protocol used can increase the functional capacity of skeletal muscle, but this effect does not appear to be related to skeletal muscle fiber hypertrophy.
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PMID:Isokinetic strength training protocols: do they induce skeletal muscle fiber hypertrophy? 335 58

Effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the activities of NAD+- or NADP+-linked dehydrogenases in the TCA cycle were studied using mitochondria prepared from mouse brains. Activities of NAD+- and NADP+-linked isocitrate dehydrogenases, NADH- and NADPH-linked glutamate dehydrogenases, and malate dehydrogenase were little affected by 2 mM of MPP+. However, alpha-ketoglutarate dehydrogenase activity was significantly inhibited by MPP+. Kinetic analysis revealed a competitive type of inhibition. Inhibition of alpha-ketoglutarate dehydrogenase may be one of the important mechanisms of MPP+-induced inhibition of mitochondrial respiration, and of neuronal degeneration.
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PMID:Inhibition of mitochondrial alpha-ketoglutarate dehydrogenase by 1-methyl-4-phenylpyridinium ion. 349 49

The purpose of this study was to investigate the effects of repeated high-intensity intermittent training programs interspaced by detraining on human skeletal muscle and performances. First, nineteen subjects were submitted to a 15-week cycle ergometer training program which involved both continuous and high-intensity interval work patterns. Among these 19 subjects, six participated in a second 15-week training program after 7 weeks of detraining. Subjects were tested before and after each training program for maximal aerobic power and maximal short-term ergocycle performances of 10 and 90s. Muscle biopsy from the vastus lateralis before and after both training programs served for the determination of creatine kinase (CK), hexokinase, phosphofructokinase (PFK), lactate dehydrogenase (LDH), malate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase (HADH) and oxoglutarate dehydrogenase (OGDH) activities. The first training program induced significant increases in all performances and enzyme activities but not in CK. Seven weeks of detraining provoked significant decreases in maximal aerobic power and maximal 90s ergocycle performance. While the interruption of training had no effect on glycolytic enzyme markers (PFK and LDH), oxidative enzyme activities (HADH and OGDH) declined. These results suggest that a fairly long interruption in training has negligeable effects on glycolytic enzymes while a persistent training stimulus is required to maintain high oxidative enzyme levels in human skeletal muscle. The degree of adaptation observed after the second training program confirms that the magnitude of the adaptive response to exercise-training is limited.
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PMID:Effects of two high-intensity intermittent training programs interspaced by detraining on human skeletal muscle and performance. 365 91

A rapid decrease in male fertility in laboratory animals exposed to 1,2-dibromo-3-chloropropane (DBCP) has been suggested to be due, in part, to a postglycolytic inhibition of sperm carbohydrate metabolism. The present studies were performed to identify the specific site of DBCP-induced inhibition of intermediary metabolism. 14CO2 generation by epididymal sperm, isolated from Fischer 344 rats, was measured using radiolabeled tricarboxylic acid (TCA) cycle intermediates: acetyl CoA, citrate, alpha-ketoglutarate, and succinate. There was 0-28% inhibition of CO2 generation after addition of 0.5 mM DBCP and 81-98% inhibition with 3 mM DBCP, with all four substrates. The activities of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase were not inhibited by DBCP. Since the DBCP-induced inhibition of metabolism of different substrates to CO2 was similar, and since DBCP did not inhibit enzyme activities of glycolysis or the TCA cycle, a common site of inhibition was suspected. In evaluations of mitochondrial electron transport chain activity, DBCP (3 mM) inhibited oxygen consumption resulting from metabolism of endogenous substrates plus alpha-ketoglutarate or malate by about 80%. When succinate, an FAD-dependent oxidation, was used as a substrate, oxygen consumption was not inhibited by DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain.
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PMID:A biochemical basis for 1,2-dibromo-3-chloropropane-induced male infertility: inhibition of sperm mitochondrial electron transport activity. 367 26

The role of heredity in the response of maximal anaerobic capacities and skeletal muscle histochemical and biochemical characteristics to a 15-week cycle ergometer training program involving both continuous and interval work patterns was investigated in 14 pairs of monozygotic twins. The training program consisted mainly of series of ergocycle supramaximal exercises lasting from 15 s to 90 s and performed 4 and 5 times a week. The subjects were submitted to 10 s and 90 s all-out ergocycle tests to estimate maximal anaerobic alactacid (AAC) and lactacid (ALC) capacities, respectively. Muscle fiber types and creatine kinase (CK), hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), 3-hydroxyacyl CoA dehydrogenase (HADH), and oxoglutarate dehydrogenase (OGDH) activities were determined in a biopsy from the vastus lateralis. Training increased AAC, ALC, fiber type I proportion, MDH, HADH, and OGDH (P less than 0.05) and decreased fiber type IIb proportion and the PFK/OGDH ratio. No significant change was observed for CK, HK, PFK, and LDH. Large interindividual differences in the response to training were observed for all variables. However, intraclass correlations indicated that the extent of the response of ALC and CK, HK, LDH, MDH, and OGDH activities and of the PFK/OGDH activity ratio to training were significantly similar within pairs of twins. Although the role of heredity appeared absent for the changes in fiber type proportions and in anaerobic alactacid capacity, the present results suggest that the response of anaerobic lactacid capacity and most enzyme activities to high-intensity intermittent training is significantly determined by the genotype.
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PMID:Inheritance of human skeletal muscle and anaerobic capacity adaptation to high-intensity intermittent training. 373 13

To determine whether sensitivity of muscle characteristics and aerobic performances to endurance training was genotype-dependent, 6 pairs of monozygotic (MZ) twins, 21 +/- 4 yr of age (mean +/- SD), took part in a 15-wk ergocycle endurance training program. Tests were performed before and after 7 and 15 weeks of training. A biopsy of the vastus lateralis muscle was obtained for the determination of fiber type composition and activities of creatine kinase, hexokinase, phosphofructokinase, lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase. Maximal oxygen uptake was measured with a progressive maximal ergocycle test, while endurance performance was determined as the total work output during a 90-min maximal ergocycle test. Results indicated that maximal oxygen uptake X kg-1 and endurance performance X kg-1 increased significantly (14 and 31%, respectively) with training, and intra-pair resemblance (intra-class) in response to 15 wk of training ranged from 0.65 to 0.83. Hexokinase (31%), phosphofructokinase (37%), lactate dehydrogenase (21%), malate dehydrogenase (31%), and 3-hydroxyacyl CoA dehydrogenase (60%) were significantly increased with training whereas no mean change in fiber-type proportions, oxoglutarate dehydrogenase and creatine kinase activities and the phosphofructokinase/oxoglutarate dehydrogenase ratio was observed. Similarity within twin pairs in the response to enzyme activities was mainly detected in the second half of the training program. The present results confirm, therefore, that both maximal oxygen uptake and endurance performance responses to training are largely genotype-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heredity and muscle adaptation to endurance training. 378 81

Five monozygotic twin pairs were submitted to a 10-week isokinetic strength training program and biochemical characteristics measured before and after training to determine the role of heredity in skeletal muscle adaptation, while 5 unrelated sedentary subjects served as control group. Experimental subjects performed twice 3 series of 5 bilateral reciprocal alternating knee flexions and extensions at a velocity of 90 degrees/s 5 times per week. Before and after the training period, for each subject, the peak muscular torque output was measured at the same velocity and the vastus lateralis muscle was biopsied for biochemical determinations. No significant change was observed in the control group. Training increased peak muscular torque output by 24%. The activities of hexokinase, malate dehydrogenase and 3-hydroxyacyl CoA dehydrogenase also increased significantly by 28, 26 and 38%, respectively. Interindividual variations in the response of these variables to training were noted but these were shown to be independent of the genotype. No overall effect of training was observed for oxoglutarate dehydrogenase activity (OGDH). However, changes were seen in individual pairs of twins and these were in opposite directions in some pairs compared to others, thus explaining the absence of a general training effect. Significant intrapair resemblance in the training response was present for OGDH (r = 0.76), indicating that the sensitivity to isokinetic strength training for OGDH was highly variable, not random and probably genetically determined.
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PMID:Inheritance of human muscle enzyme adaptation to isokinetic strength training. 379 15


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