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:1.1.1.27 (lactate dehydrogenase)
29,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lactate dehydrogenase catalyzes the stereospecific hydride transfer to and from the re face of the nicotinamide coenzyme. The demonstrated probability of transfer to the si face of less than 2 x 10(-8) indicates that the free energy of any diastereotopic transition state leading to a si transfer must be over 10 kcal/mol greater than the free energy for transfer to or from the re face. The general notion of closed, desolvated active sites suggests the a priori hypothesis that steric hindrance prevents the nicotinamide ring from assuming a conformation that would lead to transfer of the pro-S hydrogen. In this paper we report that the probability of transfer of the pro-S proton is less than 9 x 10(-7) with 3-pyridinealdehyde adenine dinucleotide as coenzyme and less than 4 x 10(-7) during the lactate dehydrogenase catalyzed disproportionation of glyoxylate. Examination of the crystal structure of lactate dehydrogenase further suggests that steric exclusion does not enforce the extreme stereospecificity of the reaction. An electrostatic interaction with the macrodipole associated with the alpha 2F helix is suggested as a potential molecular source of the stereospecificity.
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PMID:An inquiry into the source of stereospecificity of lactate dehydrogenase using substrate analogues and molecular modeling. 156 64

The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.
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PMID:Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death. 163 43

The etiology of idiopathic dilated cardiomyopathy (DCM) is yet unknown; this study aimed at further differentiation of the disease by means of enzyme histochemistry. Endomyocardial biopsies from the left ventricle of 40 DCM patients and 5 control specimens had enzymes examined histochemically and semiquantitatively and analyzed according to staining intensities of nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR), succinate dehydrogenase, cytochrome c oxidase, lactate dehydrogenase and acid phosphatase (aPh). In DCM, the NADH-TR activity was elevated as compared to controls, indicating impaired mitochondrial oxidative phosphorylation. However, a concrete relation of enzyme histochemical intensity to anamnestic, hemodynamic or histomorphometric data could not be determined, except for the fact that the intensity of the lysosomal enzyme aPh was elevated in DCM patients with a relatively high left ventricular ejection fraction. The results demonstrate an interindependence of structural, hemodynamic and historical parameters as well as enzyme concentrations in DCM. Thus, a pathological change in the enzyme concentrations tested here cannot be responsible for the functional myocardial impairment in DCM.
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PMID:Enzyme histochemistry of endomyocardial biopsies in idiopathic dilated cardiomyopathy. 165 Nov 62

Amperometric determination of nicotinamide adenine dinucleotide (reduced form) (NADH) at an immobilized-diaphorase (Dp) electrode is described. The measurement was conducted using ferrocenylmethanol as a mediator in a stirred solution at 0.20 V versus a saturated calomel electrode. A linear relationship between the steady-state current and the concentration of NADH was found over the range 0.005-0.125 mmol dm-3. The immobilized-Dp electrode showed outstanding stability and the current response reached a steady state within 2-3 seconds upon addition of NADH. The proposed electrode was used to follow the reactions of pig heart lactate dehydrogenase and horse liver alcohol dehydrogenase. The kinetic investigation using the immobilized-Dp electrode gave the kinetic parameters (Michaelis constants, Km values, and maximum velocities, Vm values), which were in satisfactory agreement with those determined by a conventional spectrophotometric method.
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PMID:Immobilized-enzyme electrode for nicotinamide adenine dinucleotide (reduced form) (NADH) sensing and application to the kinetic studies of NADH dependent dehydrogenases. 178 60

Difference spectroscopy and enzyme kinetics were employed to study the interaction of lactate dehydrogenase (LDH) from rabbit muscle with the azo-dye Procion Red HE-3B and two of its structural variants in order to follow the significance of the sulphonated terminal rings for the strength and specificity of binding. Procion Red HE-3B possesses a significantly higher affinity to LDH compared to the dye Cibacron Blue F3G-A, a well characterized pseudo-biospecific ligand of dehydrogenases. Moreover, Procion Red HE-3B showed competition towards the cofactor NAD+/NADH. The enzyme-dye complex is mainly stabilized by hydrophobic interactions, but other binding forces cannot be excluded. LDH possesses one dye-binding site per subunit. As a binding region the active center of LDH, preferentially the hydrophobic nicotinamide pocket is involved. Removal of the negatively charged sulphonic acid group from the terminal rings of Procion Red HE-3B decreases the affinity to LDH significantly but does not change the type of binding. Addition of an anilino group to the terminal rings of Procion Red HE-3B does not affect the affinity to the active site significantly but enables the binding on other sites with lower affinity in dependence on the dye concentration.
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PMID:Difference spectroscopic and kinetic studies on the interaction of lactate dehydrogenase with structurally related triazine dyes. 182 35

Mature erythrocytes, when removed from the circulation, exhibit severe disturbances of glycolytic flow, with accumulation not only of lactate, the ultimate product of glycolysis, but also of several upstream metabolic intermediates, primarily fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, and dihydroxyacetone phosphate. This accumulation may be prevented (and also reverted) by allowing the diffusible end products lactate and pyruvate to leave the cell by equilibrating with a much larger extracellular compartment. The disturbance of erythrocyte glycolysis does not result from direct inhibition by lactate itself but from the interplay between the lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase (3-PGAD) reactions. The accumulation of intermediates reflects the increased lactate-to-pyruvate ratio; this leads to a secondary imbalance of the nicotinamide adenine dinucleotide-to-reduced nicotinamide adenine dinucleotide (NAD-to-NADH) ratio, which in turn slows down glycolysis at the 3-PGAD step, whose upstream metabolites then pile up. No accumulation, however, takes place if the lactate-to-pyruvate ratio is maintained constant in the extracellular compartment, regardless of concentrations. These studies demonstrate that orderly glycolysis in the erythrocyte is regulated by the NAD-to-NADH ratio and also provide a method that makes possible the in vitro study of erythrocyte glycolysis.
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PMID:Regulation of glycolysis in the erythrocyte: role of the lactate/pyruvate and NAD/NADH ratios. 185 77

The activity of horse liver alcohol dehydrogenase was inhibited by phenylhydrazine. Kinetic experiments showed that this compound produced linear competitive inhibition with respect to NAD+ and linear noncompetitive inhibition with respect to ethanol. These results suggested that the inhibitor competes with NAD+ for the coenzyme binding site of alcohol dehydrogenase, forming a dead-end complex with the free form of the enzyme. A Ki value of 393 +/- 51 microM was estimated for the enzyme-inhibitor complex. Further evidence for this mechanism of inhibition arose from the fact that the same kind of inhibition was found for rabbit muscle lactate dehydrogenase. The Ki value for the lactate dehydrogenase-phenylhydrazine complex was 43.41 +/- 2.10 mM. The significant difference between these Ki values is explained in terms of known differences in hydrophobicity of the nicotinamide binding region in the two enzymes.
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PMID:Inhibition of horse liver alcohol dehydrogenase and rabbit muscle lactate dehydrogenase by phenylhydrazine. 185 86

A method is described for the measurement and on-line monitoring of muscular extracellular lactate concentration in both anaesthetized and freely moving rats. This method is based on microdialysis sampling and lactic dehydrogenase-catalysed nicotinamide adenine dinucleotide, reduced (NADH)-fluorescence detection techniques. In vivo calibration revealed a resting extracellular lactate concentration of 1.92 +/- 0.13 mmol/l (+/- SEM) in the gastrocnemius muscle of adult male Wistar rats (n = 6), while the average whole-blood lactate level was 0.76 +/- 0.12 mmol/l (+/- SEM). This measured extracellular lactate concentration was 1.73-times higher than that deduced from the arterial lactate concentration. Blocking glycolysis with iodoacetate reduced the extracellular lactate concentration to 52 +/- 6% (+/- SEM, n = 4) of the resting level. The extracellular lactate concentration in rat gastrocnemius muscle had increased to significantly (P less than or equal to 0.05) different levels, 2.4 +/- 0.03 (+/- SEM) or 4.0 +/- 0.55 (+/- SEM) times the control value, 1 h after aortic clamping (n = 3) or cardiac arrest (n = 3), respectively. Stimulation of the sciatic nerve induced elevations of the extracellular lactate concentration in the tibialis anterior muscle which were linearly related to the recorded isometric force-time integral. We also monitored on-line the changes in extracellular lactate concentration in the tibialis anterior muscle of a swimming rat. Our results indicate that microdialysis lactate reflects also intracellular metabolism. Lactography may be a useful alternative to biopsies and nuclear magnetic resonance spectroscopy in clinical medicine and physiology for the monitoring of metabolism in vivo.
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PMID:Continuous monitoring of extracellular lactate concentration by microdialysis lactography for the study of rat muscle metabolism in vivo. 194 55

Haemonchus contortus, incubated in 10 micrograms/ml and 50 micrograms/ml concentrations of Nilzan and albendazole in Tyrode solution were stained for histoenzymatic demonstration of various phosphatases, oxido-reductases and esterases. The intestine showed major alterations after drug treatments. The alkaline phosphatases (AkPase), adenosine triphosphatase (ATPase), glucose-6-phosphatase, succinic dehydrogenase (SDH), glutamate dehydrogenase (GDH), reduced nicotinamide adenine dinucleotide phosphate diaphorase and reduced nicotinamide adenine dinucleotide diaphorase showed a decreased activity in intestine after Nilzan treatment, whereas lactic dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PD) and monoamine oxidase resisted increased reaction. The albendazole treatment resulted in altered distribution pattern of the AkPase, ATPase, SDH, and GDH; while LDH, G-6-PD, and non-specific esterases exhibited slightly enhanced activity in the epithelium. The functional significance of these changes has been fully discussed.
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PMID:Effect of Nilzan and albendazole on the absorptive surfaces of Haemonchus contortus (Nematoda)--a histoenzymic study. 196 79

Initial velocity, product inhibition, and substrate inhibition studies suggest that the endogenous lactate dehydrogenase activity of duck epsilon-crystallin follows an order Bi-Bi sequential mechanism. In the forward reaction (pyruvate reduction), substrate inhibition by pyruvate was uncompetitive with inhibition constant of 6.7 +/- 1.7 mM. In the reverse reaction (lactate oxidation), substrate inhibition by L-lactate was uncompetitive with inhibition constant of 158 +/- 25 mM. The cause of these inhibitions may be due to epsilon-crystallin-NAD(+)-pyruvate and epsilon-crystallin-NADH-L-lactate abortive ternary complex formation as suggested by the multiple inhibition studies. Pyruvate binds to free enzyme very poorly, with a very large dissociation constant. Bromopyruvate, fluoropyruvate, pyruvate methyl ester, and pyruvate ethyl ester are alternative substrates for pyruvate. 3-Acetylpyridine adenine dinucleotide, nicotinamide 1,N6-ethenoadenine dinucleotide, and nicotinamide hypoxanthine dinucleotide serve as alternative coenzymes for epsilon-crystallin. All the above alternative substrates or coenzymes showed an intersecting initial-velocity pattern conforming to the order Bi--Bi kinetic mechanism. Nicotinic acid adenine dinucleotide, thionicotinamide adenine dinucleotide, and 3-aminopyridine adenine dinucleotide acted as inhibitors for this enzymatic crystallin. The inhibitors were competitive versus NAD+ and noncompetitive versus L-lactate. alpha-NAD+ was a noncompetitive inhibitor with respect to the usual beta-NAD+. D-Lactate, tartronate, and oxamate were strong dead-end inhibitors for the lactate dehydrogenase activity of epsilon-crystallin. Both D-lactate and tartronate were competitive inhibitors versus L-lactate while oxamate was a competitive inhibitor versus pyruvate. We conclude that the structural requirements for the substrate and coenzyme of epsilon-crystallin are similar to those of other dehydrogenases and that the carboxamide carbonyl group of the nicotinamide moiety is important for the coenzyme activity.
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PMID:Kinetic mechanism of the endogenous lactate dehydrogenase activity of duck epsilon-crystallin. 198 12


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