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  • Articles  (3)
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  • Metabolic regulation  (3)
  • 1980-1984  (3)
  • 1950-1954
  • 1983  (3)
  • Technology  (3)
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  • Articles  (3)
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  • 1980-1984  (3)
  • 1950-1954
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  • 1983  (3)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 11 (1983), S. 361-384 
    ISSN: 1573-9686
    Keywords: Enzymes ; Simulation ; Fatty acid metabolism ; Metabolic regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A computer model of the fatty acid oxidation pathway in perfused rat heart was constructed. It includes uptake, activation, and β-oxidation of fatty acids, triglyceride synthesis and hydrolysis, and carnitine-dependent transport of acyl groups across the mitochondrial membrane under pseudosteady state conditions. Fatty acid utilization may be limited by β-oxidation in hypoxia or ischemia but probably not in aerobic conditions. Nonesterified fatty acids bound to proteins are found to be metabolically available. The model predicts that stearate, but not palmitate, can support the highest observed respiration rate for perfused rat heart without supplementation by other substrates. Fatty acids are preferentially oxidized rather than being stored as triglycerides because the cystosolic acyl CoA level is lower than the Km for triglyceride synthesis. It is suggested that feedback inhibition of triglyceride lipase regulates utilization of triglycerides as fuel in aerobic hearts.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 11 (1983), S. 511-531 
    ISSN: 1573-9686
    Keywords: Enzymes ; Simulation ; Fatty acid metabolism ; Glycolysis ; Citric acid cycle ; Metabolic regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Intermediary metabolism in rat hearts persfused with 11 mM glucose plus 1 mM palmitate was simulated by a computer model. Several enzyme submodels in a previous version of the isolated rat heart computer model wre improved, and a new fatty acid oxidation pathway model was added. Compartmentation of metabolites in a pseudostationary state was calculated, and its implications are discussed, e.g., citrate level may not regulate glycolysis because it is mostly mitochondrial. Citrate synthetase, controlled largely by its inhibitors, is of key importance in regulating fatty acid metabolism. The response of aconitase to the mitochondrial Mg2+ levels is of major importance in setting both the mitochondrial citrate and isocitrate levels. Pyruvate dehydrogenase is about 96% in the inactive phosphorylated form, and the active form is also 15% inhibited by products, severely limiting pyruvate oxidation and causing preferential utilization of palmitate as the metabolic fuel. The simulation is consistent with a creatine phosphate shuttle which delivers high energy phosphate to the site of its utilization for mechanical work.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 11 (1983), S. 533-549 
    ISSN: 1573-9686
    Keywords: Sensitivity analysis ; Metabolic regulation ; Fatty acid utilization ; Glucose utilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The behavior of a computer model of metabolism in glucose- and palmitate-perfused rat hearts was interpreted by sensitivity analysis to explain why the heart preferentially utilizes fatty acids as fuel even in the presence of substantial exogenous glucose. The sensitivity functions identified those metabolites and enzymes which were most important in regulating the metabolic rate and determined which enzymes set the levels of the critical metabolites. Control of the mitochondrial redox potential and the distribution of coenzyme A thioesters regulated the rate of fatty acid utilization while strong inhibition of citrate synthetase resulted in accumulation of acetyl CoA and supprersion of pyruvate oxidation. Glycolysis was limited by the cytosolic ATP/ADP ratio set largely by the creatine shuttle. Metabolic control appears to be widely distributed rather than localized at “key” enzymes. Metabolite levels are usually set by enzymes controlled by modifiers whereas metabolic flux is regulated by the enzymes that produce ligands for the modifier-controlled enzymes.
    Type of Medium: Electronic Resource
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