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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Doxorubicin (Adriamycin, ADR) is an anthracycline antineoplastic with the serious side effect of dose-related cardiomyopathy. A model of ADR cardiotoxicity was created to examine some subcellular toxic effects of ADR with cultured cardiac myocytes (CMCs) exposed to 1 x 10(-7) to 1 x 10(-5) M ADR for 24 to 48 hr. Lactate dehydrogenase (LDH) activity was monitored in the CMC medium to monitor CMC damage as a function of ADR concentration. A four- to eightfold elevation of LDH activity in medium of CMCs exposed to 1 x 10(-6) to 1 x 10(-5) M ADR was found. No change in LDH activity was detected in medium of CMCs exposed to 1 x 10(-7) M ADR or in control CMCs after 24 or 48 h ADR exposure. Data suggest a dose-dependent effect of ADR on LDH activity in CMC medium. Serial monitoring of LDH in media of ADR-exposed CMCs may correlate with other evidence of ADR cardiotoxicity in vitro.
Exp Mol Pathol 1988 Jun
PMID:Lactate dehydrogenase activity in cultured neonatal rat heart cells exposed to doxorubicin. 337 55

The effect of beta-adrenergic stimulation on myocardial fatty acid metabolism was studied in the anesthetized open-chest dog. Isoproterenol (1 microgram/kg/min) was infused; and samples of arterial blood and of left ventricular wall were taken at the 5th min for the determination of the following variables: in arterial blood: lactate and serial free fatty acids (FFA); in myocardial tissue: creatine phosphate (CP), ATP, lactate, carnitine, acylcarnitine, glycerol, and the fatty acid content of each of phospholipids (PL), cholesterol esters (CE), triglycerides (TG), diglycerides (DG), monoglycerides (MG), and FFA. A capillary gas chromatography was used for fatty acid assay. Isoproterenol decreased the content of creatine phosphate but not of ATP. Lactate increased in both arterial blood and myocardial tissue. The five-fold increase in arterial FFA (P less than 0.001) was accompanied with a significant increase in FFA serum/tissue ratio. Free carnitine decreased and acylcarnitine increased. Triglycerides content (which is expressed in terms of its total fatty acid content) was considerably reduced by beta-stimulation in comparison with control group (2694 +/- 689 vs. 7518 +/- 833 nmol/g wet wt, P less than 0.001), and tissue glycerol increased (P less than 0.01). The decrease in total MG content was significant, but not that of DG, nor that of CE. Total PL content did not change. The most marked individual changes (except in PL) were observed on monounsaturated fatty acids, 18: 1 omega 9, 18: 1 omega 7, and 16: 1 cis. The significant changes of monounsaturated/saturated and of 16:1 cis/16:1 trans ratios, in arterial FFA and tissue TG, suggested modifications in the distribution of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Feb
PMID:Effect of isoproterenol on the metabolism of myocardial fatty acids. 357 44

Glucose utilization by different metabolic pathways in bovine adrenal medulla has been studied using freshly isolated adrenal chromaffin cells. The rate of net glucose utilization in resting cells was 10.5 mumoles X g-1 X h-1. 50% was transformed into lactate and pyruvate, the lactate to pyruvate ratio ranging from 3 to 7.27% was metabolized through the tricarboxylic acid cycle and 3.1% was oxidized in the pentose phosphate pathway. The ratio of 14CO2 production from [1-14C] glucose and [6-14C] glucose was close to 2 at one hour of incubation. 3.2% of total glucose consumed was used in protein synthesis, and 1% was incorporated into lipids. Oxygen utilization in respiration by isolated adrenal chromaffin cells was 18.2 mumoles X g-1 X h-1, corresponding to 3.1 mumoles glucose X g-1 X h-1 or about 30% of total glucose consumed. The activities of hexokinase, enolase, pyruvate kinase, lactate dehydrogenase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were assayed in extracts of bovine adrenal medulla, being 1.0, 23, 40, 37, 6.0 and 3.0 U/g respectively. Hexokinase activity was identified as belonging mainly to isoenzyme I, with some isoenzyme II. Enolase was predominantly the alpha gamma hybrid. Pyruvate kinase activity corresponded to a mixture of isoenzymes K and M. Lactate dehydrogenase activity corresponded to isoenzymes 1, 2 and 3, with smaller proportions of isoenzymes 4 and 5. Results are discussed mainly with respect to those reported for the brain.
Mol Cell Biochem 1986 Apr
PMID:Enzymes and pathways of glucose utilization in bovine adrenal medulla. 371 7

Trypanosoma cruzi (epimastigotes), Crithidia fasciculata and Leishmania mexicana (promastigotes) were grown in a brain-heart-tryptose medium supplemented with heat-inactivated fetal calf serum. T. cruzi and C. fasciculata utilized glucose completely during the log phase of growth, whereas L. mexicana used significant amounts of the carbohydrate only at the end of the log phase and at the beginning of the stationary phase. In all cases glucose consumption resulted in excretion of succinate, and much smaller amounts of acetate. C. fasciculata and L. mexicana produced very small amounts of pyruvate. C. fasciculata produced ethanol, which was taken up again and metabolysed after glucose was exhausted. Lactate and malate were not produced. The cells were disrupted by sonic disintegration, and the activities of some key enzymes of carbohydrate and amino acid catabolism were assayed in the whole homogenates. Phosphoenolpyruvate carboxykinase was present in the three organisms; L. mexicana presented the highest specific activity. The activity of this enzyme was maximal during glucose consumption, and slightly decreased after glucose was exhausted. This suggests that the role played by the enzyme is glycolytic and not gluconeogenic; the latter is the case in most higher organisms. Hexokinase and pyruvate kinase presented their highest levels in C. fasciculata and T. cruzi during glucose consumption. L. mexicana, which was in active glycolysis during the whole experimental period, presented the highest specific activities of both enzymes. Citrate synthase, on the other hand, increased in C. fasciculata and, to a lesser extent, in T. cruzi, after glucose was exhausted; the enzyme could not be detected in L. mexicana. The NAD-linked glutamate dehydrogenase increased considerably in C. fasciculata and T. cruzi after glucose was exhausted, suggesting a catabolic role for the enzyme. This increase coincided with an increase in NH3 production by both organisms after glucose consumption. The NADP-linked glutamate dehydrogenase, on the other hand, presented a maximum about the time when glucose was exhausted, and then decreased again, which suggests a catabolic role for the enzyme. Both glutamate dehydrogenases had low activities in L. mexicana; this fits in well with the low NH3 production throughout the culture of this organism. The results are in good agreement with current ideas on the mechanism of aerobic glucose fermentation by trypanosomatids, and suggest that, under the experimental conditions used, both T. cruzi and C. fasciculata used glucose perferentially over amino acids for growth.
Mol Biochem Parasitol 1985 Sep
PMID:End products and enzyme levels of aerobic glucose fermentation in trypanosomatids. 390 97

High concentrations of lactate and oxfenicine inhibit fatty acid oxidation in cardiac muscle. The site of this inhibition was investigated in isolated perfused rat hearts. In hearts perfused with glucose (11 mM) and [U-14 C]palmitate (1.0 mM), addition of 5 mM lactate caused a 38% reduction in 14CO2 production. Tissue levels of long-chain acyl carnitine decreased suggesting that inhibition occurred at either fatty acyl CoA synthetase or carnitine-acyl CoA transferase. Cytosolic levels of acyl-CoA are low compared with mitochondrial levels and changes in acyl-CoA within the cytosolic compartment cannot be estimated directly. Consequently, the rate of conversion of 14C-palmitate to neutral lipids was used as an indicator of cytosolic acyl CoA levels. Lactate caused a 100% increase in 14C-fatty acid conversion to triglycerides suggesting that cytosolic levels of acyl-CoA increased in association with decreased acyl-carnitine. This indicates that lactate inhibited FFA oxidation at the level of carnitine-acyl CoA transferase. Oxfenicine (2 mM) reduced fatty acid oxidation by 45%, decreased acyl-carnitine levels by 80%, and increased conversion of 14C-palmitate to neutral lipids by 44%, suggesting that oxfenicine also inhibits fatty acid oxidation at the level of carnitine-acyl CoA transferase. These data further indicate that carnitine-acyl CoA transferase is an important site of control in the pathway of fatty acid oxidation.
J Mol Cell Cardiol 1985 Jun
PMID:Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle. 392 8

Lactate dehydrogenase (LDH) and LDH isoenzyme activities were determined in tumor tissue, tumor cystic fluid, and serum from athymic mice with transplants of a human testicular germ cell tumor. High activity of LDH-1 was found in tumor tissue and tumor cystic fluid. By histochemical staining LDH was found in all tumor cells. Most tumor cells had a faint staining reaction while some cells dispersed throughout the tumor had a strong staining reaction. The serum LDH-1 in athymic mice with tumor transplants correlated markedly with the tumor volume. The results indicate that serum LDH-1 was derived from the testicular germ cell tumor transplants.
Mol Gen Genet 1982
PMID:Lactate dehydrogenase isoenzyme 1 (LDH-1) in athymic mice with xenografts of a human testicular germ cell tumor. 628 49

Lactate dehydrogenase of Fasciola hepatica showed typical Michaelis-Menten kinetics at pH 7.2, with respect to pyruvate. Addition of physiological levels of fructose bisphosphate activated the enzyme at all substrate concentrations tested; the response to this effector being hyperbolic in nature. As well as depending upon the fructose bisphosphate concentration, the Vmax and Km are modified by different buffers. The degree of activation is much greater using Tris-HCl than phosphate buffer. The pH optimum occurs at pH 6.5 whether using physiological levels of substrate in the presence or absence of fructose bisphosphate, or high levels of substrate. Of the potential effectors tested, significant inhibition was shown by the nucleoside triphosphates, especially ATP. The importance of this inhibition, coupled with the activation by fructose bisphosphate is discussed. Fasciola hepatica lactate dehydrogenase is unusual in that it does not catalyse the reverse reaction to any measurable extent. That is, lactate oxidation is negligible unless the effector fructose bisphosphate is present. Use was made of this fact to visualise the isoenzymes of lactate dehydrogenase separated by polyacrylamide disc gel electrophoresis. Five isoenzyme bands became apparent when stained in this manner.
Mol Biochem Parasitol 1983 Mar
PMID:A fructose bisphosphate activated lactate dehydrogenase in the liver fluke Fasciola hepatica. 688 26

Lactate dehydrogenase (LDH) from Plasmodium falciparum was partially purified by two different procedures. In the first procedure, parasitized erythrocytes (80% parasitemia) were lysed, and the soluble fraction was purified on DEAE-Sephadex to separate the parasite LDH(LDH-P) from the LDH isoenzymes present in the human erythrocytes. LDH-P was then purified by high-performance liquid chromatography (HPLC) on a TSK-G-3000 SW protein column. This two-step procedure gave LDH-P with specific activity 85 micromol/min/mg protein; this represented a 700-fold increase in specific activity relative to the starting lysate. Alternatively, parasites of P. falciparum were isolated by mechanical rupture of infected erythrocytes followed by differential centrifugation. The 100,000 X g supernatant obtained after lysis of these parasites showed LDH-P specific activity 3.6 micromol/min/mg protein. This activity was free of contaminating erythrocyte LDH as determined by electrophoresis and specific staining for LDH. Further purification of LDH-P by HPLC, as before, gave material with specific activity 98 micromol/min/mg protein. Recoveries of activity on HPLC were more than 90%, demonstrating the usefulness of this procedure for the partial purification of small quantities of parasite protein. The kinetic properties of LDH-P were compared with those of two of the human isozymes, LDH-H4 and LDH-M4 . LDH-P resembles LDH-H4 in its kinetic properties: KM (NADH) is 7, 8.3 and 1.3 microM for LDH-P, LDH-H4 and LDH-M4, respectively; KM (pyruvate) is 30, 60 and 180 microM for LDH-P, LDH-H4 and LDH-M4. LDH-P differs significantly from LDH-H4 and LDH-M4 in that LDH-P is not sensitive to inhibition by high pyruvate nor sensitive to inhibition by the complex between NAD+ and pyruvate. LDH-P is inactivated within seconds by sodium deoxycholate at concentrations that do not affect LDH-H4 and slowly inactivate LDH-M4.
Mol Biochem Parasitol 1981 Dec 31
PMID:Partial purification and characterization of lactate dehydrogenase from Plasmodium falciparum. 703 78

The effects of L-arginine on recovery of myocardial contractile function and oxidative metabolism were investigated in a model of reversible global normothermic, ischemic injury using an isolated, buffer-perfused rabbit heart preparation. One mM L-arginine was infused into hearts for 2 min at the onset (group 1) of a 35 min period of ischemia or at the onset of reperfusion (group 2). In non-ischemic hearts, L-arginine caused a slight increase in developed pressure but had no effects on diastolic pressure, oxygen consumption (MVO2), coronary flow, or lactate production. When administered either before or after ischemia-reperfusion. L-arginine caused a significant increase in the diastolic pressure-volume relationship (PVR) and decline in systolic function when compared to untreated control hearts receiving the same ischemic injury. Recovery of MVO2 and high energy phosphates (phosphocreatine and ATP), measured by 31P-NMR spectroscopy, were significantly impaired in L-arginine-treated hearts compared to reperfused control hearts. Lactate release on reperfusion was also higher in both arginine-treated groups. Nitric oxide release into the coronary circulation (measured in separate experiments by the conversion of [15N]L-arginine to [15N]nitrate/nitrite using gas chromatography/mass spectroscopy) was not increased by L-arginine administration. Thus, we conclude that L-arginine acts synergistically with ischemia reperfusion to augment myocardial injury, which includes inhibition of oxidative metabolism and mitochondrial function.
J Mol Cell Cardiol 1995 Jul
PMID:Direct detrimental effects of L-arginine upon ischemia--reperfusion injury to myocardium. 747 86

Lactate dehydrogenase (LDH) is highly active in filariae and could be a valuable tool for phyllogeny studies. Unfortunately, the isoenzymatic diagnosis of filariae is often difficult for LDH because of a poor mobility of the enzymes in starch gels which are the most commonly used in such studies. We propose here a method to separate filarial LDH isoenzymes using disc electrophoresis. The experiments were carried out on male and female Molinema dessetae in order to compare their respective isoenzymes. The study of several parameters such as buffer systems, percentage of bisacrylamide and progression time led to optimize the enzyme separation. LDH from male and female filariae were compared to mammal LDH-H4 and LDH-M4. Five and four LDH isoenzymes were found, respectively, in male and female worms. Relative concentration of each isoenzyme diverged between male and female worms. Mammal muscle LDH-M4 type moved between LDH2 and LDH3 from female worms, and between LDH1 and LDH2 from male worms. Mammal heart H4 type enzyme was very different in electrophoretic mobility. The ratio of each isoenzyme was determined by densitometry. The major isoenzymes from female worms will be studied as a biochemical target for chemotherapeutic attack.
Comp Biochem Physiol B Biochem Mol Biol
PMID:Isoenzymatic diagnosis of filariae: a method for separation of lactate dehydrogenase isoenzymes from Molinema dessetae (Nematoda: Filarioidea). 755 54


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