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ATP Generation (atp + generation)
Selected AbstractsIschaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pigACTA PHYSIOLOGICA, Issue 1 2010A. Waldenström Abstract Aim:, ,Pre-treatment' with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods:, A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with 14C- adenosine with two different specific activities. 14C-lactate was identified and measured in the effluent. Results:,14C-adenosine was taken up by non-preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of 14C-lactate were recovered in preconditioned myocardium. 14C-adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of 14C-adenosine with low specific activity. Mass spectrography verified the identity of 14C-lactate. Conclusions:, Preconditioning up-regulates a new metabolic pathway (starting with 5,-nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up-regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved. [source] AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectivesACTA PHYSIOLOGICA, Issue 1 2009B. Viollet Abstract As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome. [source] Analysis of the factors related with mate choice and reproductive success in male three-spined sticklebacksJOURNAL OF FISH BIOLOGY, Issue 5 2000E. R. Cubillos Territorial three-spined sticklebacks moved 5·3 times as far as non-territorial males in 2 min (P < 0·001) and spent 11·1 times longer in aggression in the pools (P< 0·001). Territorial males had slightly higher condition factors than non-territorial males. Condition factor was correlated positively with the gonad mass (P< 0·006), carotenoid concentration (P< 0·006) and the activity of CS in the axial muscle (P< 0·05) and lactate dehydrogenase (LDH) in pectoral muscle (P < 0·003). The male traits best correlated positively with female mate choice were courtship effort (P< 0·001), coloration (P< 0·003) and initial condition (P< 0·025). Courtship behaviour was related to intestine mass (P< 0·018), axial (P< 0·028) and pectoral muscle citrate synthase (CS) activity (P< 0·047); coloration was related to gonad mass (P< 0·037). These muscle enzymes may be involved in ATP generation for sustained activities or in recuperation between bouts of burst activity. Females that choose to mate with assiduously courting males which bear higher CS levels may be choosing individuals that show honestly their good condition and capacity to accomplish reproductive tasks. [source] Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicityJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2007David G. Nicholls Abstract The pathologic activation of NMDA receptors by glutamate is a major contributor to neuronal cell death after stroke. Receptor activation causes a massive influx of calcium into the neuron that is accumulated by the mitochondria. The favored hypothesis is that the calcium loaded mitochondria generate reactive oxygen species that damage and ultimately killed the neuron. In this review this hypothesis is critically re-examined with an emphasis on the role played by deficits in ATP generation. Novel techniques are developed to monitor the bioenergetic status of in situ mitochondria in cultured neurons. Applying these techniques to a model of glutamate excitotoxicity suggests that enhanced reactive oxygen species are a consequence rather than a cause of failed cytoplasmic calcium homeostasis (delayed calcium deregulation, [DCD]), but that prior oxidative damage facilitates DCD by damaging mitochondrial ATP generation. This impacts on current hypotheses relating to the neuroprotective effects of mild mitochondrial uncoupling. © 2007 Wiley-Liss, Inc. [source] Ketones: Metabolism's Ugly DucklingNUTRITION REVIEWS, Issue 10 2003Theodore B. Vanitallie MD Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, dietinduced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders. [source] Prior heavy exercise eliminates slow component and reduces efficiency during submaximal exercise in humansTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005K. Sahlin We investigated the hypothesis that the pulmonary oxygen uptake slow component is related to a progressive increase in muscle lactate concentration and that prior heavy exercise (PHE) with pronounced acidosis alters kinetics and reduces work efficiency. Subjects (n= 9) cycled at 75% of the peak for 10 min before (CON) and after (AC) PHE. was measured continuously (breath-by-breath) and muscle biopsies were obtained prior to and after 3 and 10 min of exercise. Muscle lactate concentration was stable between 3 and 10 min of exercise but was 2- to 3-fold higher during AC (P < 0.05 versus CON). Acetylcarnitine (ACn) concentration was 6-fold higher prior to AC and remained higher during exercise. Phosphocreatine (PCr) concentration was similar prior to exercise but the decrease was 2-fold greater during AC than during CON. The time constant for the initial kinetics (phase II) was similar but the asymptote was 14% higher during AC. The slow increase in between 3 and 10 min of exercise during CON (+7.9 ± 0.2%) was not correlated with muscle or blood lactate levels. PHE eliminated the slow increase in and reduced gross exercise efficiency during AC. It is concluded that the slow component cannot be explained by a progressive acidosis because both muscle and blood lactate levels remained stable during CON. We suggest that both the slow component during CON and the reduced gross efficiency during AC are related to impaired contractility of the working fibres and the necessity to recruit additional motor units. Despite a pronounced stockpiling of ACn during AC, initial kinetics were not affected by PHE and PCr concentration decreased to a lower plateau. The discrepancy with previous studies, where initial oxidative ATP generation appears to be limited by acetyl group availability, might relate to remaining fatiguing effects of PHE. [source] | ||||||||||