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Lipogenesis from ketone bodies and glucose in developing brain
196
SY~IPOSIUM 3
Nutrient and Metabolic Requirements of the Developing Central Nervous System Edmond, J. Organizer, Biol. Chem., UCLA School of Medicine, I.os Angeles, CA
90024,USA
The metabolic capacity of the developing central nervous system for the major functions of energy production and lipogenesis is to be presented from several perspectives. Emphasis is to be placed on the development and regulation of enzymes which are critical to energy metabolism and to the biosynthesis of lipids, particularly of cholesterol. Complementary to the discussions of enzymic capacities which reflect metabolic potential will be presentations dealing with studies which identify the fuels of cerebral energy metabolism and the substrates which serve as significant carbon sources for lipogenesis during active myelination. Model systems which permit the study of metabolic capacity in a discrete way, and lead to the understanding of central nervous system function in terms of the metabolic specialization of specific cell populations., the metabolic function and capacity of discrete brain regions and the compartmentation of metabolic processes at the subcellular level will all be highlighted in delineating nutrient requirements for the course of development.
Development of enzymes of energy metabolism in mammalian brain Clark, J.B., Booth, R.F.G., Leong, S.F., Munday, L.A., Patel, T.B. Medical College of St. Bartholomew's Hospital, University of London, Biochemistry Department, Charterhouse Square, London, U.K. Our interests lie in the mechanisms whereby the mammalian brain develops the biochemical capability for the expression of full neurological competence. In particular, we have focussed on energy metabolism and the development of the activities of key enzymes involved in glucose and ketone body metabolism. The problem has been approached by studying enzyme development in two systems, a) in a precocial and non-precocial species - guinea pig and rat, b) in a number of different regions of a single species - rat. Our studies show that the enzyme complement of the guinea pig brain is much more highly developed at birth than that of the rat. Furthermore, within the rat brain, the enzyme complement of certain areas, e.g. medulla oblongata, develops much earlier than in other regions. This may correlate with the early development of neurological activity in this region and the need for a fully active aerobic glycolysis to be available for neurological maturity. This work has been supported by the MRC (R.F.G.B.), SERC (L.A.M.,T.B.P.) and the British Council (S.F.L.)
LIPOGENESIS FROMKETONEBODIESAND GLUCOSE IN DEVELOPING BRAIN J. Edmond, N.S. Auestad, J.D. Bergstrom, R.A. Cole, and J. de Vellis Mental Retardation Research Center, UCLA School of Medicine, Los Angeles, CA 90024 The ketone bodies, acetoacetate and D(-)-3-hydroxybutyrate in addition to glucose are available as substrates for lipogenesis and energy metabolism at a time of active growth and myelination in developing brain. Our research has focused on delineating the metabolic demands of brain for these metabolites to establish p r i o r i t i e s for their u t i l i z a t i o n . Two approaches have been taken. (1) Studies in vivo with rat pups reared by t h e i r mother, or reared a r t i f i c i a l l y [W.G. Hall, Science 190, 1313 (1975)] on rat milk substitutes, formulated s p e c i f i c a l l y to provide a normal or hypoketonemic condition, show the importance of ketone bodies for brain development. Pups reared on the hypoketonemic diet have reduced sulfatide in brain. There is a small but s i g n i f i cant reduction in the mass of brain cholesterol and a perturbation of the biosynthesis of cholesterol in s i t u is indicated by a reduction in the pool size of i t s precursor, desmosterol. (2-) Studies with g l i a l cell populations prepared from 2-day old rat brain [McCarthy and de V e l l i s , J. Cell Biol. 85, 890 (1980)] and maintained in primary culture for periods up to 30 days show that acetoacetate is an excellent substrate for both respiration and sterol synthesis; glucose by contrast was not a good substrate under comparable conditions but was used effectively in the pentose phosphate shunt. Supported in part by USPHS grants HD 06576, HD 05615 and HD I1496.
SY~IPOSIUM 3
Nutrient and Metabolic Requirements of the Developing Central Nervous System Edmond, J. Organizer, Biol. Chem., UCLA School of Medicine, I.os Angeles, CA
90024,USA
The metabolic capacity of the developing central nervous system for the major functions of energy production and lipogenesis is to be presented from several perspectives. Emphasis is to be placed on the development and regulation of enzymes which are critical to energy metabolism and to the biosynthesis of lipids, particularly of cholesterol. Complementary to the discussions of enzymic capacities which reflect metabolic potential will be presentations dealing with studies which identify the fuels of cerebral energy metabolism and the substrates which serve as significant carbon sources for lipogenesis during active myelination. Model systems which permit the study of metabolic capacity in a discrete way, and lead to the understanding of central nervous system function in terms of the metabolic specialization of specific cell populations., the metabolic function and capacity of discrete brain regions and the compartmentation of metabolic processes at the subcellular level will all be highlighted in delineating nutrient requirements for the course of development.
Development of enzymes of energy metabolism in mammalian brain Clark, J.B., Booth, R.F.G., Leong, S.F., Munday, L.A., Patel, T.B. Medical College of St. Bartholomew's Hospital, University of London, Biochemistry Department, Charterhouse Square, London, U.K. Our interests lie in the mechanisms whereby the mammalian brain develops the biochemical capability for the expression of full neurological competence. In particular, we have focussed on energy metabolism and the development of the activities of key enzymes involved in glucose and ketone body metabolism. The problem has been approached by studying enzyme development in two systems, a) in a precocial and non-precocial species - guinea pig and rat, b) in a number of different regions of a single species - rat. Our studies show that the enzyme complement of the guinea pig brain is much more highly developed at birth than that of the rat. Furthermore, within the rat brain, the enzyme complement of certain areas, e.g. medulla oblongata, develops much earlier than in other regions. This may correlate with the early development of neurological activity in this region and the need for a fully active aerobic glycolysis to be available for neurological maturity. This work has been supported by the MRC (R.F.G.B.), SERC (L.A.M.,T.B.P.) and the British Council (S.F.L.)
LIPOGENESIS FROMKETONEBODIESAND GLUCOSE IN DEVELOPING BRAIN J. Edmond, N.S. Auestad, J.D. Bergstrom, R.A. Cole, and J. de Vellis Mental Retardation Research Center, UCLA School of Medicine, Los Angeles, CA 90024 The ketone bodies, acetoacetate and D(-)-3-hydroxybutyrate in addition to glucose are available as substrates for lipogenesis and energy metabolism at a time of active growth and myelination in developing brain. Our research has focused on delineating the metabolic demands of brain for these metabolites to establish p r i o r i t i e s for their u t i l i z a t i o n . Two approaches have been taken. (1) Studies in vivo with rat pups reared by t h e i r mother, or reared a r t i f i c i a l l y [W.G. Hall, Science 190, 1313 (1975)] on rat milk substitutes, formulated s p e c i f i c a l l y to provide a normal or hypoketonemic condition, show the importance of ketone bodies for brain development. Pups reared on the hypoketonemic diet have reduced sulfatide in brain. There is a small but s i g n i f i cant reduction in the mass of brain cholesterol and a perturbation of the biosynthesis of cholesterol in s i t u is indicated by a reduction in the pool size of i t s precursor, desmosterol. (2-) Studies with g l i a l cell populations prepared from 2-day old rat brain [McCarthy and de V e l l i s , J. Cell Biol. 85, 890 (1980)] and maintained in primary culture for periods up to 30 days show that acetoacetate is an excellent substrate for both respiration and sterol synthesis; glucose by contrast was not a good substrate under comparable conditions but was used effectively in the pentose phosphate shunt. Supported in part by USPHS grants HD 06576, HD 05615 and HD I1496.