Partial oxidation of leucine in skeletal muscle

1. Leucine and its 2-oxo analogue, 4-methyl-2-oxopentanoate, increased the release of acetoacetate and 3-hydroxybutyrate from hemidiaphragms isolated from 40 h-starved rats. Glucose and lactate+pyruvate decreased basal and leucine-stimulated rates of ketone body production. 2. The production of acetoacetate + 3-hydroxybutyrate in response to addition of leucine was suppressed in hemidiaphragms from fed rats. 3. At 3 mM leucine, for each mumol of leucine oxidized in the branched-chain 2-oxo acid dehydrogenase reaction (measured as 14CO2 production from [1-14C]leucine), 0.84 mumol of acetoacetate + 3-hydroxybutyrate were produced. This stoichiometry may imply that acetoacetate derived from the partial oxidation of leucine is not further oxidized in situ. The physiological significance of these findings is discussed.