Health Worlds

One. Lactate metabolism
Landlord you may be wrong, dichloroacetic acid is pyruvate dehydrogenase complex of agonist, it facilitates the formation of pyruvate metabolism of acetyl-CoA, inhibit the formation of lactic acid.Dichloroacetic acid salt - development of new drugs
American University of Florida College of Medicine Dr. Yan Zimeng Summary
Dichloroacetic acid salt is a new drug candidate in the research stage, but it is also a number of chlorinated organic compounds (such as trichloroethane, TCA) and drugs (such as chloramphenicol, chloral hydrate) and metabolites, and water by-product of chlorination. In recent years the drug by the United States, Canada, Switzerland, Austria, Ghana, Britain and Japan and other countries concerned, and its treatment in a variety of diseases and side effects were significant experimental study and clinical evaluation. This drug is known mainly for cardiovascular and metabolic diseases, such as myocardial or cerebral ischemia, diabetes, congenital lactic acidosis or other compensatory therapeutic effect, and its toxicological studies are mainly from the environmental health perspective, evaluate their impact on human health. 80 years on the drug situation in previous studies reed by Stacpoole. In this paper, since the 90's Progress on the drug.
1, the rationale and clinical application activity
Glucose oxidation in the body during the acetyl coenzyme A, pyruvate lactate and alanine metabolism in connecting the important


intermediates. Pyruvate dehydrogenase complex is the process of glucose and pyruvate oxidation rate-limiting enzyme, which catalyzes the oxidative decarboxylation of pyruvate to produce acetyl coenzyme A. This process is oxidation of glucose into the Krebs cycle and the regulation of metabolism of lactic acid and alanine, an important step, as shown in Figure 1. Regulation of pyruvate dehydrogenase by substrate (pyruvate, ADP) activated, end products (acetyl coenzyme A, NADH) and reversible inhibition of phosphorylation, the inhibition of phosphorylation, dephosphorylation activation. Magnesium and calcium ions of pyruvate dehydrogenase phosphatase can be excited, so that in the dephosphorylation of pyruvate dehydrogenase (active) state. Pyruvate dehydrogenase kinase were acetyl coenzyme A, NADH, and activated protein kinase excitement, and is coenzyme A, NAD, ADP, pyruvate, and dichloroacetic acid suppression [1-3].
Dichloroacetic acid is pyruvate dehydrogenase complex of agonist, which by inhibiting pyruvate dehydrogenase kinase to activate the pyruvate dehydrogenase complex. Under normal physiological conditions, lactic acid, alanine and pyruvate in equilibrium between. In the case of tissue hypoxia, caused by intense exercise, such as hypoxia and high lactate levels, dichloroacetic acid salt can increase the oxygen uptake, pyruvate dehydrogenase complex excited to promote lactic acid oxidation, additional energy supply, thereby improving the lack of Organization of energy metabolism of oxygen [4-5]; and myocardial or cerebral ischemia, glucose oxidation for energy shortage in the circumstances, to improve the energy supply, can ease the symptoms of cardiac or cerebral ischemia. Based on the above role, dichloroacetic acid salt on cardiovascular and cerebrovascular diseases have therapeutic implications. On the other hand, dichloroacetic acid salts for the treatment of metabolic diseases is through the promotion of lactic acid oxidation, reduce blood lactate levels, improve metabolism of the body's acid-base balance, relieve symptoms of acidosis, such as congenital or compensatory (such as malaria caused by) lactic acidosis.
According to the pharmacological activity of dichloroacetic acid salt, animal experiments and clinical research for heart and cerebrovascular diseases, diabetes, and various diseases caused by lactic acidosis. Animal experiments showed that dichloroacetic acid salt can increase the myocardial oxygen uptake and oxidative phosphorylation, increased myocardial efficiency, thus improving the energy metabolism of ischemic myocardium and function. In the promotion of lactic acid oxidation, increase energy supply while reducing lactic acid levels also help reduce the hypoxic acidosis [6-7]. Clinical studies also show that, dichloroacetic acid salt can improve cardiac hemodynamic indexes, increased oxygen utilization, and reduce peripheral vascular resistance [8,9]. Caused by mitochondrial abnormalities of cerebral metabolism disorders, the use of dichloroacetic acid salt, a week of short-term treatment, oral administration of a dose of 25mg/kg, 2 times a day. The drug not only lowers blood lactate, pyruvate and alanine levels, but also significantly reduced brain lactate / creatine ratio, increased choline / creatine and N-acetyl aspartate / creatine ratio; on for brain oxidative metabolism, neural and glial function has a significant role [10]. In addition, dichloroacetic acid salts in experimental animals has a protective effect of cerebral ischemia [11], but also alleviate the central nervous system caused by ischemia and lactic acidosis, improve nerve electrophysiological function [12].
Dichloroacetic acid salt on the treatment of diabetes, the significance of its role in lowering blood glucose and fat. The drug can cell metabolism to fat oxidation to glucose oxidation mainly into the main. This shift is because the salt of dichloroacetic acid associated with insulin-like effects of three: 1. Excited glycolysis; 2. For glucose oxidation; 3. Inhibition of fatty acid oxidation. Carried out on rats and mice in the experiment, dichloroacetic acid salt type diabetes and b, , or V-hyperlipoproteinemia effect of lowering triglycerides. In addition, dichloroacetic acid salt is rate-limiting enzyme of cholesterol synthesis - hydroxymethyl glutamyl coenzyme A reductase inhibitor, non-competitive, but its mechanism is unclear. Diabetes, dichloroacetic acid salt can lower blood sugar, lactic acid, alanine and -hydroxybutyrate levels, inhibition of glycogen synthesis, and can reduce insulin requirements. As for the dichloroacetic acid salt is suitable for long-term for the treatment of clinical diabetes, its side effects, dosage and time interval to be further explored [3].
Congenital deficiency of mitochondrial enzymes of lactic acid


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