The research is designed to determine: 1) the mecahnism of beta-hydroxybutyrate (BetaHB) transport in cell plasma membranes and in the blood-brain barrier, b) the mechanism by which BetaHB permeability of the blood-brain barrier is enhanced in ketonic states, and c) the biological significance of this moulation. Kinetic studies of BetaHB entry into erythrocytes and thymocytes will seek to gain evidence for the BetaHB negative/H positive symport mechanism, which, if it operates, can be distinguished from the BetaHB negative/OH negative antiport mechnism under conditions which favor formation and manifestation of the unprotonated Beta HB:carrier complex. We will examine the possible role of the inorganic-anion-exchange carrier in erythrocyte BetaHB transport. Possible dietary modulations of BetaHB transport in erythrocytes and thymocytes will be examined. The monocarboxylate carrier of erythrocytes will be solubilized and reconstituted in liposomes in hopes of purifying and characterizing the carrier. Information on the basic mechanism of BetaHB transport in erythrocytes and thymocytes will be used to help determine the mechanism of cerebral BetaHB-transport modulations. The intra-carotid injection technique will be used to measure cerebral BetaHB transport in normal and fat-fed rats, and alterations of the injectant solution will be used to test hypotheses concerning the transport mechanism of its modulation. The effects of capillary-to-brain BetaHB transport on the brain:serum distribution of other permeants will be examined to determine the transport partner(s) of BetaHB. The effects of the modulation on cerebral BetaHB utilization and glucose utilization will be examined.