Control Factors Affecting Gluconeogenesis in Perfused Rat Liver

作者：JOHN R. WILLIAMSON, Stephen G. Rostand, Michael J. Peterson · 发表于：Journal of Biological Chemistry · 年份：1970 · DOI：10.1016/s0021-9258(18)63046-7 · 被引用次数：68 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolism, Diabetes, and Cancer、Adipose Tissue and Metabolism

The metabolism and mechanism of action of 4-pentenoic acid has been investigated in isolated perfused rat livers.4-Pentenoic acid (up to 10 Imoles per g of liver) was rapidly metabolized with the consumption of slightly more than 2 g atoms of oxygen per mole of 4-pentenoic acid added and production of 0.5 mole of ketone bodies.Addition of larger amounts of 4-pentenoic acid resulted in an incomplete metabolism.Tissue levels of coenzyme A and carnitine fell by 83% and 70%, respectively, within 1 min after 4-pentenoic acid addition.Acid-soluble acyl-CoA and acylcarnitine compounds increased rapidly, but subsequently declined so that after 45 min most of the bound CoA and carnitine derivatives were present in the perchloric acid-insoluble form.Acetyl-CoA levels initially fell moderately whereas acetylcarnitine levels showed a transient rise during the period of rapid ketone body production.These results are in accordance with previous suggestions in the literature that 4-pentenoic acid is first converted to 4-pentenyl-CoA which then undergoes one step of fl oxidation with the production of acetyl-CoA, acrylyl-CoA, and their carnitine derivatives.Acrylyl-CoA probably undergoes further metabolism since the amount of 4-pentenoic acid metabolized is far greater than the CoA and carnitine contents of the liver.Metabolism of 4-pentenoic acid was associated with inhibitions of both long and short chain fatty acid oxidation, pyruvate oxidation, gluconeogenesis, and the citric acid cycle....