Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this work was to evaluate the biochemical changes in the myocardial cell using cardioplegia supplemented with creatine phosphate (CP). Many previous studies have demonstrated the beneficial effect of CP on the ischemic myocardium and its mechanism of action has been assumed to be mainly extracellular. Based on the assumption that CP could also exert some influence on myocardial cellular metabolism, this investigation was carried out. Forty patients undergoing mitral valve replacement were divided into two groups: group 1 was treated with standard cardioplegic solution, and group 2 was treated with cardioplegic solution enriched with CP at a concentration of 10 mmol/L. Samples of papillary muscle, obtained from the removed valve, were studied by means of biochemical methods in order to assess the enzyme activities and the metabolites of the different biochemical pathways related to energy metabolism in the myocardial cell. One papillary muscle sample was used to determine enzyme activities spectrophotometrically; another was used to evaluate metabolite concentrations by spectrophotometric or spectrophotofluorimetric methods. The rate of spontaneous functional recovery after rewarming and weaning from cardiopulmonary bypass (CPB) also was evaluated. In group 2, the Vmax of enzymatic activities was significantly greater (hexokinase, malate dehydrogenase, glutamate dehydrogenase, total NADH cytochrome c reductase) and a better functional state of the heart was observed after CPB. On the basis of the clinical and biochemical data, it is concluded that the myocardium was better preserved when CP was added to the cardioplegic solution. Therefore, the results suggest a possible interaction of exogenous CP with cellular metabolism.
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PMID:Biochemical changes induced in the myocardial cell during cardioplegic arrest supplemented with creatine phosphate. 193 52

Carnitine is a naturally occurring compound that is essential in energy metabolism of the mammalian heart. In addition to its essential role in facilitating beta-oxidation, carnitine eliminates excess toxic acyl residues and regulates the mitochondrial acetyl coenzyme A (CoA)/CoA ratio. Thus, it is not surprising that patients with carnitine deficiency syndromes exhibit defects in energy metabolism and in some cases demonstrate left ventricular dysfunction. Pivalic acid is commonly used to create prodrugs, such as pivampicillin and pivmecillinam, to facilitate enteral absorption and increase oral bioavailability. Pivalic acid released from the drug following absorption readily forms an ester with carnitine, which is then excreted as pivaloylcarnitine. Sustained loss of carnitine in the form of this ester induces a state of carnitine deficiency, exemplified by low plasma and tissue carnitine content. This review examines the effects in the rat of short- and long-term sodium pivalate treatment on: (1) cardiac carnitine content; (2) in vitro mechanical function; (3) markers of glycolytic and fatty acid metabolism; and (4) energy substrate metabolism. Treatment with sodium pivalate induces a gradual loss of cardiac carnitine content for up to 12 weeks. Doubling the duration of treatment is not associated with any further decrease in cardiac carnitine content. While heart function following short-term treatment (2 weeks) is normal under aerobic conditions, impaired recovery of function following ischaemia is seen. In contrast, long-term treatment (11-28 weeks) is associated with impaired heart function, which is dependent on workload and substrate availability. Impaired heart function is also associated with reductions in activity of 3-hydroxyacyl CoA dehydrogenase and rates of fatty acid oxidation. However, to maintain adenosine triphosphate production, glucose metabolism, expressed as hexokinase activity and glucose oxidation, is increased in carnitine-deficient hearts. Hearts from sodium pivalate-treated animals demonstrate a cardiomyopathy that is dependent on duration of treatment, workload and substrate supply. This model of hypocarnitinaemia may thus be useful to study the metabolic and cardiac consequences of carnitine-deficiency syndromes.
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PMID:Hypocarnitinaemia induced by sodium pivalate in the rat is associated with left ventricular dysfunction and impaired energy metabolism. 1675 41