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Dehydrogenase Kinase (dehydrogenase + kinase)

Distribution by Scientific Domains
Life Sciences40%

Kinds of Dehydrogenase Kinase

  • pyruvate dehydrogenase kinase
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    Selected Abstracts

    Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    ACTA PHYSIOLOGICA, Issue 1 2007
    J. W. Helge
    Abstract Aim:, Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. Methods:, Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 ± 11 years; cycling o2peak: males 57.4 ± 5.9, females 48.1 ± 4.0 mL kg,1 min,1). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. Results:, After the race fat mass was decreased by 1.6 ± 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 ± 0.06 and 0.93 ± 0.03 before, to 0.71 ± 0.01 and 0.85 ± 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 ± 74 to 1407 ± 118 ,mol L,1; P < 0.01). Muscle glycogen content fell 50% (from 554 ± 28 to 270 ± 25 nmol kg,1 d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 ± 5 to 22 ± 3 mmol kg,1 d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor , co-activator-1, mRNA tended to be lower (P = 0.06). Conclusion:, Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes. [source]

    Metabolic gene switching in the murine female heart parallels enhanced mitochondrial respiratory function in response to oxidative stress

    FEBS JOURNAL, Issue 20 2007
    M. Faadiel Essop
    The mechanisms underlying increased cardioprotection in younger female mice are unclear. We hypothesized that serine-threonine protein kinase (protein kinase B; Akt) triggers a metabolic gene switch (decreased fatty acids, increased glucose) in female hearts to enhance mitochondrial bioenergetic capacity, conferring protection against oxidative stress. Here, we employed male and female control (db/+) and obese (db/db) mice. We found diminished transcript levels of peroxisome proliferator-activated receptor-alpha, muscle-type carnitine palmitoyltransferase 1 and pyruvate dehydrogenase kinase 4 in female control hearts versus male hearts. Moreover, females displayed improved recovery of cardiac mitochondrial respiratory function and higher ATP levels versus males in response to acute oxygen deprivation. All these changes were reversed in female db/db hearts. However, we found no significant gender-based differences in levels of Akt, suggesting that Akt-independent signaling mechanisms are responsible for the resilient mitochondrial phenotype observed in female mouse hearts. As glucose is a more energetically efficient fuel substrate when oxygen is limiting, this gene program may be a crucial component that enhances tolerance to oxygen deprivation in female hearts. [source]

    Identification of ERR, as a specific partner of PGC-1, for the activation of PDK4 gene expression in muscle

    FEBS JOURNAL, Issue 8 2006
    Makoto Araki
    Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulatory enzyme involved in switching the energy source from glucose to fatty acids in response to physiological conditions. Transcription of the PDK4 gene is activated by fasting or by the administration of a PPAR, ligand in a tissue-specific manner. Here, we show that the two mechanisms are independent, and that ERR, is directly involved in PPAR,-independent transcriptional activation of the PDK4 gene with PGC-1, as a specific partner. This conclusion is based on the following evidence. First, detailed mutation analyses of the cloned PDK4 gene promoter sequence identified a possible ERR,-binding motif as the PGC-1, responsive element. Second, overexpression of ERR, by cotransfection enhanced, and the knockout of it by shRNAs diminished, PGC-1,-dependent activation. Third, specific binding of ERR, to the identified PGC-1, responsive sequence was confirmed by the electrophoresis mobility shift assay. Finally, cell-type-specific responsiveness to PGC-1, was observed and this could be explained by differences in the expression levels of ERR,, however, ectopic expression of ERR, in poorly responsive cells did not restore PGC-1, responsiveness, indicating that ERR, is necessary, but not sufficient for the response. [source]

    Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl,CoA dehydrogenase (MCAD),deficient mice,

    HEPATOLOGY, Issue 6 2008
    Hilde Herrema
    Medium-chain acyl,coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD,/, mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD,/, mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1, (Pgc-1,) and decreased peroxisome proliferator-activated receptor alpha (Ppar ,) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD,/, mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD,/, mice. During the APR, however, this flux was significantly decreased (,20%) in MCAD,/, mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD,/, mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD,/, mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD,/, mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.) [source]

    Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats

    THE JOURNAL OF PHYSIOLOGY, Issue 6 2008
    N. Alamdari
    A characteristic manifestation of sepsis is muscle lactate accumulation. This study examined any putative (causative) association between pyruvate dehydrogenase complex (PDC) inhibition and lactate accumulation in the extensor digitorum longus (EDL) muscle of rats infused with lipopolysaccharide (LPS), and explored the involvement of increased transcription of muscle-specific pyruvate dehydrogenase kinase (PDK) isoenzymes. Conscious, male Sprague,Dawley rats were infused i.v. with saline (0.4 ml h,1, control) or LPS (150 ,g kg,1 h,1) for 2 h, 6 h or 24 h (n= 6,8). Muscle lactate concentration was elevated after 2, 6 and 24 h LPS infusion. Muscle PDC activity was the same at 2 h and 6 h, but was 65% lower after 24 h of LPS infusion (P < 0.01), when there was a 47% decrease in acetylcarnitine concentration (P < 0.05), and a 24-fold increase in PDK4 mRNA expression (P < 0.001). These changes were preceded by marked increases in tumour necrosis factor-, and interleukin-6 mRNA expression at 2 h. The findings indicate that the early (2 and 6 h) elevation in muscle lactate concentration during LPS infusion was not attributable to limited muscle oxygen availability or ATP production (evidenced by unchanged ATP and phosphocreatine (PCr) concentrations) or to PDC inhibition, whereas after 24 h, muscle lactate accumulation appears to have resulted from PDC activation status limiting pyruvate flux, most probably due to cytokine-mediated up-regulation of PDK4 transcription. [source]