Mitochondrial/cytosolic carbon transfer in the developing rat brain.

The rates of citrate and acetoacetate efflux from rat brain mitochondria (synaptic and free) utilizing different substrates (pyruvate, 3-hydroxybutyrate or acetoacetate) under different conditions have been studied as a function of development. In general there were no marked differences in the acetoacetate efflux rates between 'free' and 'synaptic' brain mitochondria whereas citrate efflux rates were usually higher in 'free' mitochondria. Developmental studies with brain mitochondria utilizing 3-hydroxybutyrate + malate showed a profile for acetoacetate efflux which was at a peak at weaning (21 days) and then decreased by 50% in the adult state. Similar studies measuring citrate efflux showed little change as the brain developed, but when pyruvate + malate were used as substrates the citrate efflux doubled during the period 5--20 days and was then maintained in the adult state. Phenylpyruvate was found to inhibit both acetoacetate and citrate efflux from 21-day-old and adult rat brain mitochondria when they used either 3-hydroxybutyrate or pyruvate as substrate. It is concluded that ketone bodies may be potentially as effective, if not better, than glucose in the brain of the suckling rat as precursors of cytosolic biosynthetic activities whereas in the adult rat brain, ketone bodies are relatively poor precursors of these activities.