Fatty Acid Metabolism

Recent experiments with isotopically labeled fatty acids (2-6) make it reasonably certain that ketone bodies arise from these substances in liver by coupling of acetyl groups which result from p oxidation.With the establishment of the acetyl group as the most probable primary breakdown product of fatty acids, the question emerges whether condensation to acetoacetate is an obligatory step in the metabolism of acetate in all tissues and under all conditions, or whether further chemical changes may occur mithout intermediary conversion to ketone bodies.The present investigation was designed to elucidate this question.A preliminary study disclosed that liver, kidney, and heart muscle slices of the rat readily metabolize aceta,e + ,I but only with liver is there accumulation of ketone bodies.Comparison of the relative rates of acetate and acetoacetate disappearance in these organs revealed that whereas in liver there was little if any disappearance of ketone bodies, the rate of acetoacetate breakdown in kidney and heart is so rapid compared with acetate metabolism, that ketone bodies, if formed from the latter, would not be expected to accumulate.Thus, no answer can be acquired by this method as to whether or not ketone bodies are actually formed during acetate metabolism in kidney and heart.With sodium acetate, marked by the presence of excess Cl3 in the carboxyl carbon, the conversion of acetat,e to acetoacetate in these two tissues was tested in t,he following way.A mixture of isotopic acetate and normal, non-isotopic acetoacetat,e was incubated with the tissue for 2 hours in oxygen at 38", the quantity of acetoacetate taken being such as to allow the recovery of an amount sufficient for isotope analysis at the close of the *A preliminary report. of this work has appeared (1).With the technical assistance of Lafayette Noda, Mary Cammaroti, Ethel Niessen, and Ruth Millington.Aided in part by Mr. Paul A. Davis of Philadelphia. 1 Experiments were also carried out with rat brain and skeletal muscle slices, but acetate utilization was so low in these tissues that further work with them appeared fruitless.