Lactic dehydrogenase, inhibition

Enzymes activities are particularly sensitive to the anticoagulant used in collecting the specimen. Heparin inhibits acid phosphatase (W16) and muramidase (Z5). Amylase activity is inhibited by oxalate or citrate (MIO), and lactic dehydrogenase and acid phosphatase lose activity in oxalate (C2). Alkaline phosphatase is stable in oxalate, oxalate-fluoride, or heparin, but 25 mAf citrate inhibits 50% of the activity, and as little as 50 mlf EDTA is completely inhibitory (B19). Leucine aminopeptidase is inhibited by EDTA, as is creatine phosphokinase (F3). Amylase activity has been reported to be only 83% of that in serum when oxalate or citrate-plasma is used (MIO). Heparin plasma appears to have no inhibitory effect. Despite the fact that clotting factor V is not stable in oxalate or EDTA, these are often used as anticoagulants to obtain plasma for prothrombin determinations (Z2, Z4). 

CS causes alkylation of sulfhydryl-containing enzymes and inhibits lactic dehydrogenase, glutamic dehydrogenase, pyruvic decarboxy-. lase, and alpha-glycerophosphate dehydrogenase.24,40 it reacts with a number of nucleophilic compounds, such as glutathione, plasma protein, and lipoic acid.24... 

Cucinell et aJL. 3 reversed the CS inhibition of lactic dehydrogenase in dogs by injecting sodium thiosulfate. Rats poisoned by CS at 80 mg/kg (more than the LD50) were saved by injections of thiosulfate. Cucinell e a l. speculated that the toxic effects of CS were caused by inhibition of sulfhydryl-containing enzymes. 

NADH as an end product. This implicates oxidized malic acid, either pyruvic or oxaloacetic acid, as another end product. By adding commercial preparations of L-lactic dehydrogenase or malic dehydrogenase to the reaction mixture, Morenzoni (90) concluded that the end product was pyruvic acid. Attempts were then made to show whether two enzymes—malate carboxy lyase and the classic malic enzyme, malate oxidoreductase (decarboxylating), were involved or if the two activities were on the same enzyme. The preponderance of evidence indicated that only one enzyme is involved. This evidence came from temperature inactivation studies, heavy-metal inhibition studies, and ratio measurements of the two activities of partially purified preparations of Schiitz and Radlers malo-lactic enzyme (76, 90). This is not the first case of a single enzyme having two different activities (91). 

APG has been used to inhibit bovine heart lactic dehydrogenase, egg white lysozyme, horse liver alcohol dehydrogenase, and yeast alcohol dehydrogenase (Ngo etal., 1981), in cross-linking RNA—protein interactions in E. coli ribosomes (Politz et al., 1981), and in identifying regions of brome mosaic virus coat protein chemically cross-linked in situ to viral RNA (Sgro et al., 1986). 

An elderly man who had been taking allopurinol 300 mg daily for 12 years developed fever and marked increases in his serum levels of lactic dehydrogenase and alkaline phosphatase within a day of starting to take tamoxifen 10 mg twice daily. He rapidly recovered when the allopurinol was stopped. The reasons for the reaction are not understood, but the authors suggested that the increased hepatotoxic effect may have resulted from tamoxifen inhibiting allopurinol metabolism, thereby increasing the serum levels of allopurinol and its metabolite. The general importance of this isolated report is not known. 

This inhibitor can even discriminate between isoenzymes. Thus, whereas it irreversibly inhibits the lactic dehydrogenase of skeletal muscle, it does not affect that of the heart. A related compound, 5-(phenoxycarbonylamino)salicylic acid, irreverisbly inhibits the heart (but not the skeletal) isoenzyme, whereas its 4-isomer irreversibly inhibits the skeletal (but not the heart) isoenzyme (Baker and Patel, 1964 Baker, 1967). 

The demonstration by Phillips and Laiigdon (1956) that the level of TPNH-cytochromc c reductase is increased in the livers of hyperthyroid rats and reduced in those of hypothyroid animals is of particular interest. Since the activity of this enzyme results in the production of triphospho-pyridiiie nucleotide (TPN), a cofactor required for many oxidative enzymes, this change is probably a direct reflection of the general over-all acceleration of oxidative processes, and, more specifically, of those which are TPN-linked. Decreased activity of lactic dehydrogenase (Vcstling and Knocpfelmacher, 1950) is compatible with the demonstrated ability of thyroxine to inhibit this enzyme in vitro (Wolff and Wolff, 1957 Radsma et al., 1957). Decreases in the in vivo activity of such enzymes as tyrosine oxidase, DOPA-decarboxylase, betaine-homocysteine transmethylase, and... 

Grisiola S, Rubio V, Eeijoo B et al (1975) Inhibition of lactic dehydrogenase and of pyruvate kinase by low concentrations of quercetin. Physiol Chem Phys 7 473 75... 

Exposure of leukemia P388 to act-D causes respiratory depression, a decrease in malic and lactic dehydrogenase and an Increase in glucose-6-phosphate dehydrogenase. These effects are similar to those caused by nitrogen mustard.93 Act-D stimulates isoperoxidase activity at low concentration and represses it at higher concentration. It inhibits the activity of DNA polymerase.95... 

Narcotic drugs, especially barbiturates, inhibit lactic dehydrogenase in brain cortex, apparently by competing with it for the substrate (Quastel and Wheatley, 1933). 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples, this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (Fig. 7.84). The first step is catalyzed by the enzyme alcohol dehydrogenase, and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate, and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation, glucose metabolism, Krebs cycle, protein synthesis, RNA synthesis, and DNA replication. 

Lactic acidosis. Patients in shock will often suffer from lactic acidosis due to a deficiency of O2. Why does a lack of O2 lead to lactic acid accumulation One treatment for shock is to administer dichloroacetate, which inhibits the kinase associated with the pyruvate dehydrogenase complex. What is the biochemical rationale for this treatment ... 

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