OXIDATION OF GLUCOSE and D-B-OH-BUTYRATE BY THE EARLY HUMAN FETAL BRAIN

Abstract. Adam, P. A. J., Räihä, N., Rahiala, E.-L. and Kekomäki, M. (Departments of Pediatrics, Case Western Reserve University at Cleveland Metropolitan General Hospital, Cleveland, Ohio USA, and the University of Helsinki at the Children's Hospital, Helsinki, Finland). Oxidation of glucose and D-B-OH-butyrate by the early human fetal brain. Acta Paediatr Scand, 64:17, 1975.–The isolated brains of 12 previable human fetuses obtained at 12 to 21 weeks' gestation, were perfused through the interval carotid artery with glucose (3 mM) and/or DL-B-OH-butyrate (DL-BOHB), 4.5 mM, plus tracer quantities of either glucose-6-¹⁴C (G6¹⁴C) or β-OH-butyrate-3-¹⁴C (BOHB3¹⁴C). Oxidative metabolism was demonstrated by serial collection of gaseous ¹⁴CO₂ from the closed perfusion system, and from the recirculating medium. Glucose and BOHB were utilized at physiological rates as indicated (mean ±SEM): G6¹⁴C at 0.10±0.01 μmoles/min g brain (n=7) or 17.5±1.9 μmoles/ min kg fetus; and BOHB3¹⁴C at 0.16±0.05 μmoles/min g (n=5) or 27.3±7.4 μmoles/ min kg. Based on fetal weight, glucose metabolism by brain apparently accounted for about 1/3 of basal glucose utilization in the fetus. On a molar basis BOHB3¹⁴C was taken up at 1.47 times the rate of G6¹⁴C. Both BOHB3¹⁴C and G6 ¹⁴C were converted to ¹⁴C0₂. The rate of BOHB3¹⁴C conversion to ¹⁴CO₂ was equal to its rate of consumption, and exceeded the conversion of glucose to CO₂ because 45% of the G6¹⁴C was incorporated into lactate-¹⁴C. Accordingly, both substrates support oxidative metabolism by brain; and BOHB is a major potential alternate fuel which can replace glucose early in human development.