The fuel of respiration of rat kidney cortex.
1. In kidney-cortex slices from the well-fed rat, glucose (5mm) supplied 25-30% of the respiratory fuel; in the starved state, the corresponding value was 10%. These results are based on measurements of the net uptake of glucose and of the specific radioactivity of labelled carbon dioxide formed in the presence of [U-(14)C]-glucose. 2. Added acetoacetate (5mm) or butyrate (10mm) provided up to 80%, and added oleate (2mm) up to 50% of the fuel of respiration. The oxidation of endogenous substrates was suppressed correspondingly. 3. More [U-(14)C]oleate was removed by the tissue than could be oxidized by the amount of oxygen taken up; less than 25% of the oleate removed was converted into respiratory carbon dioxide and about two-thirds was incorporated into the tissue lipids. The rate of oleate incorporation into the neutral-lipid fraction was calculated to be equivalent to the rate of oxidation of endogenous fat, which provided the chief remaining fuel. 4. The contribution of endogenous substrates to the respiration (50%) in the presence of added oleate is taken to reflect either a high turnover rate of the endogenous neutral lipids (approx. half-life 2.5hr.) or a raised rate of lipolysis caused by the experimental conditions in vitro. 5. Added l-alpha-glycerophosphate (2.5mm) increased oleate incorporation into the neutral-lipid fraction by up to 40% (i.e. caused a net synthesis of triglyceride). 6. Lactate (2.5mm) added as sole substrate supplied 30% of the respiratory fuel, but with added oleate (2mm) lactate was converted quantitatively into glucose. Oleate stimulated the rate of gluconeogenesis from lactate by 45%. 7. The oxidation of both long-chain and short-chain even-numbered fatty acids was accompanied by ketone-body formation. Ketone-body synthesis from oleate, but not from butyrate, increased six- to seven-fold after 48hr. of starvation. The maximum rates of renal ketogenesis (80mumoles/hr./g. dry wt., with butyrate) were about 20% of the maximum rates observed in the liver (on a weight-for-weight basis) and accounted for, at most, 35% of the fatty acid removed. 8. dl-Carnitine (1.0mm) had no effect on the rates of uptake of acetate, butyrate or oleate or on the rate of radioactive carbon dioxide formation from [U-(14)C]oleate, but increased ketone-body formation from oleate by more than 100%. Ketone-body formation from butyrate was not increased. 9. There is evidence supporting the assumption that there are cells in which gluconeogenesis and ketogenesis occur together, characterized by equal labelling of [U-(14)C]oleate and the ketone bodies formed, and other cells that oxidize fat and do not form ketone bodies. 10. Inhibitory effects of unlabelled acetoacetate on the oxidation of [1-(14)C]butyrate and of unlabelled butyrate on [4-(14)C]acetoacetate oxidation show that fatty acids and ketone bodies compete as fuels on the basis of their relative concentrations. 11. The pathway of ketogenesis in renal cortex must differ from that of the liver, as beta-hydroxy-beta-methylglutaryl-CoA synthetase is virtually absent from the kidney. In contrast with the liver the kidney possesses 3-oxo acid CoA-transferase (EC 2.8.3.5), and the ready reversibility of this reaction and that of thiolase (EC 2.3.1.9) provide a mechanism for ketone-body formation from acetyl-CoA. This mechanism may apply to extrahepatic tissues generally, with the possible exception of the epithelium of the rumen and intestines.
D000090:Acetoacetates / Q000378:metabolism*; D000818:Animals; D002087:Butyrates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D002331:Carnitine / Q000494:pharmacology; D004032:Diet; D004040:Dietary Carbohydrates; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005994:Glycerophosphates / Q000494:pharmacology; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D009829:Oleic Acids / Q000378:metabolism*; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D012710:Serum Albumin, Bovine; D013217:Starvation / Q000378:metabolism; D013268:Stimulation, Chemical; D014166:Transferases / Q000378:metabolism
D000090:Acetoacetates; D002087:Butyrates; D002247:Carbon Isotopes; D004040:Dietary Carbohydrates; D005227:Fatty Acids; D005994:Glycerophosphates; D007657:Ketone Bodies; D007773:Lactates; D008055:Lipids; D009829:Oleic Acids; D011773:Pyruvates; D002245:Carbon Dioxide; D012710:Serum Albumin, Bovine; D014166:Transferases; D005947:Glucose; D002331:Carnitine