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)

We have previously shown that acute coronary occlusion in the dog is often accompanied by increased adrenaline release into the blood. In the present study the consequences of this humoral reaction were studied in anaesthetised healthy mongrel dogs subjected to adrenaline infusion administered at a rate relevant to spontaneous release of this amine in coronary occlusion. Adrenaline was infused in a dose of 1.2 microgram.kg-1.min-1 for 4 h. Dogs receiving saline served as the control. Adrenaline administration led to the decrease in insulin/glucose ratio, to a significant fall in serum triiodothyronine and in blood pH. Free fatty acid levels doubled. Histochemically, a diminution in succinic dehydrogenase and ATPase activity in adrenaline-treated hearts was found. A significant fall in the activity of mitochondrial hexokinase in these hearts was detected spectrophotometrically. Electron microscopic study revealed alterations in the mitochondrial structure. These findings indicate that an excess of adrenaline in ammounts similar to that seen in experimental infarction leads to profound metabolic and hormonal disturbances and exerts a detrimental effect upon myocardium.
Cardiovasc Res 1978 Mar
PMID:Evidence for the detrimental effect of adrenaline infused to healthy dogs in doses imitating spontaneous secretion after coronary occlusion. 2 14

Tracer techniques have provided new insight in cardiology by allowing noninvasive studies of myocardial perfusion, function, metabolism, and, more recently, ligand-receptor interaction. Positron emission tomography allows accurate quantification and the use of natural substrates labelled with 11C, 13N, or 15O. Myocardial metabolism is complex and utilizes a number of substrates, primarily fatty acids. Fatty acids utilization can be studied with 11C palmitate, while 11C acetate more selectively traces TCA cycle activity and reflects myocardial oxygen utilization. Glucose uptake can be traced using 18F deoxyglucose, a glucose analog that is a substrate for hexokinase but is not further metabolized. Flow and oxidative glucose metabolism are usually coupled, and thereby the uptake of FDG and perfusion tracers are usually similar. In myocardial ischemia, however, glucose utilization can persist due to anaerobic glycolysis, and its uptake is frequently enhanced. Clinical applications of the use of metabolic studies in patients with ischemic heart disease are presented.
Cardiovasc Drugs Ther 1990 Aug
PMID:Imaging of myocardial metabolism by positron emission tomography. 209 80

This work was designed to test whether phosphofructokinase is a target for emetine action on the heart. The effects of 37 microM emetine on the activities of phosphofructokinase and hexokinase were measured in homogenates from perfused hearts. The action of increasing concentrations of emetine was determined in nonperfused heart homogenates. The effect of 37 microM emetine or control solutions on the concentration of fructose-6-phosphate and fructose- 1,6-phosphate was measured. The effect of 37 microM emetine or control perfusion on the utilization of fructose-6-phosphate by phosphofructokinase in centrifugation supernatants of homogenates and in reconstituted 27,000g pellets was measured. Double-reciprocal plots of fructose-6-phosphate concentrations vs phosphofructokinase activities were plotted. Emetine decreased phosphofructokinase activity in homogenates from both perfused and nonperfused hearts. Emetine did not inhibit cardiac hexokinase activity. In homogenates from nonperfused hearts, the maximal inhibition with high concentrations of emetine was approx 50%. Emetine perfusion caused a simultaneous increase in the phosphofructokinase substrate fructose-6-phosphate and a decrease in the phosphofructokinase product fructose-1,6-bisphosphate. Phosphofructokinase and, consequently, glycolytic flux appear to be subcellular targets for emetine in the heart. Homogenate centrifugation studies indicate that emetine acts on bound rather than unbound phosphofructokinase. The inhibition may be uncompetitive in nature.
Cardiovasc Toxicol 2003
PMID:Emetine inhibits glycolysis in isolated, perfused rat hearts. 1473 28

Cardiac glucose metabolism is critical to hypoxic cardiac function and hypoxia is known to stimulate glucose metabolism. This increases generation of ATP when mitochondrial respiration is inhibited. In diabetes, cardiac glucose metabolism declines and this may contribute to diabetic cardiomyopathy. The first step in committing glucose to metabolism is glucose phosphorylation catalyzed by hexokinase. But the potential role of hexokinase in the hypoxic or diabetic heart is uncertain. This study is designed to assess the ability of hexo-kinase and elevated ATP to protect cardiomyocyte contractility from hypoxia and diabetes. We used cardiomyocytes from the transgenic mouse Mh, which has cardiac specific expression of yeast hexokinase, to investigate the importance of glucose phosphorylation in the myocyte response to hypoxia and diabetes. Cardiomyocytes were isolated from FVB control and Mh hearts to assess the effects of 2 h of hypoxia on myocyte contractility and ATP content. The protective effect of hexokinase on diabetes was assessed in myocytes from the OVE26 Type I diabetic mouse and in OVE26Mh diabetic mice that carry the hexokinase gene. Overexpression of hexokinase had no effect during aerobic culture, but during hypoxia, hexokinase improved ATP content by 44% and this restored contractility almost to normal levels. In myocytes from diabetic mice, tested under both aerobic and hypoxic conditions, the hexokinase gene significantly improved ATP content and this significantly improved contractility. These results demonstrate that elevating hexokinase activity can be beneficial to hypoxic or diabetic cardiomyocytes secondary to improving myocyte ATP levels.
Cardiovasc Toxicol 2005
PMID:Overexpression of hexokinase protects hypoxic and diabetic cardiomyocytes by increasing ATP generation. 1624 74

Decoctions and infusions of Artocarpus communis (Forst) (family: Moraceae) root bark are traditionally used among the Yoruba-speaking people of western Nigeria as folk remedies for the management, control and treatment of an array of human diseases, including type 2 diabetes mellitus. Although numerous bioactive prenylflavonoids have been isolated from the roots, stem bark and leaves of A communis, to the best of our knowledge, the effects of the plant's root bark extract on animal models of diabetes mellitus have hitherto not been reported in the biomedical literature. In our pilot study, we observed that A communis root bark aqueous extract (ACE) raised blood glucose concentrations in rats. In view of this finding, the present study was undertaken to investigate the glycaemic effect of ACE in comparison with that of streptozotocin (STZ) in Wistar rats. Four groups (A, B, C and D) of Wistar rats, each group consisting of 10 rats, were used in this study. Group A rats received distilled water in quantities equivalent to the volume of ACE administered. Diabetes mellitus was induced in the animals in groups B and C by intraperitoneal (ip) injections of STZ (75 mg/kg body weight). The rats in group C were additionally treated with ACE (50 mg/kg body weight ip) from the third to the tenth day following STZ treatment. Group D rats received ACE (12.5-100 mg/kg body weight ip) only. The effects of ACE were compared with those of STZ on blood glucose concentrations, serum and pancreatic insulin levels, hepatic hexokinase (HXK) and glucokinase (GCK) activities, and hepatic glycogen contents in the experimental animal paradigm used. The rats in treated groups B, C and D exhibited pronounced polyuria, hypo-insulinaemia and hyperglycaemia. Group D rats developed significant hyperglycaemia (p < 0.05) immediately after ACE administration, whereas groups B and C rats became hyperglycaemic 24 to 72 hours post STZ and STZ + ACE treatments, when compared with the control group A rats. Hepatic glycogen contents significantly increased (p < 0.05), while HXK and GCK activities significantly decreased (p < 0.05) in the treated groups B, C and D rats, when compared with the control group A rats. The findings of this laboratory animal study indicate that A communis root bark aqueous extract induced acute hyperglycaemia in Wistar rats, and that it disrupted the biochemical variables of the rat pancreas and liver.
Cardiovasc J Afr
PMID:Hyperglycaemic effect of Artocarpus communis Forst (Moraceae) root bark aqueous extract in Wistar rats. 1794 Jun 66

Biological actions resulting from phosphoinositide synthesis trigger multiple downstream signalling cascades by recruiting proteins with pleckstrin homology domains, including phosphoinositide-dependent kinase-1 and protein kinase B (also known as Akt). Retrospectively, more attention has been focused on the plasma membrane-associated interactions of these molecules and resulting cytoplasmic target activation. The complex biological activities exerted by Akt activation suggest, however, that more subtle and complex subcellular control mechanisms are involved. This review examines the regulation of Akt activity from the perspective of subcellular compartmentalization and focuses specifically upon the actions of Akt activation downstream from phosphoinositide synthesis that influence cell biology by altering nuclear signalling leading to Pim-1 kinase induction as well as hexokinase phosphorylation that, together with Akt, serves to preserve mitochondrial integrity.
Cardiovasc Res 2009 May 01
PMID:Nuclear and mitochondrial signalling Akts in cardiomyocytes. 1927 64

The central role of mitochondria as mediators of cell survival is indisputable and gathering increasing attention as a focal point for interventional strategies to mitigate apoptotic cell death in the wake of cardiomyopathic injury. A legacy of signal transduction studies has proven that mitochondrial integrity can be enhanced by kinases involved in cell survival. Among the many survival signaling cascades under investigation, the wide-ranging impact of Akt upon mitochondrial biology is well known. However, despite years of investigation, emerging research continues to reveal new mechanisms governing the protective effects of Akt signaling in the context of cardiomyocyte mitochondria. This review focuses on two emerging pathways that mediate preservation of mitochondrial function downstream of Akt: hexokinase and Pim-1 kinase.
Expert Rev Cardiovasc Ther 2009 Aug
PMID:Mitochondrial integrity: preservation through Akt/Pim-1 kinase signaling in the cardiomyocyte. 1967 71