Acetate transport and utilization in the rat brain.
Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brain in vivo during infusion of [2-13C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMR(ace)) increased progressively and reached close to saturation for plasma acetate concentration > 2-3 mM, whereas brain acetate concentration continued to increase. The Michaelis-Menten constant for brain acetate utilization (K(M)(util) = 0.01 +/- 0.14 mM) was much smaller than for acetate transport through the blood-brain barrier (BBB) (K(M)(t) = 4.18 +/- 0.83 mM). The maximum transport capacity of acetate through the BBB (V(max)(t) = 0.96 +/- 0.18 micromol/g/min) was nearly twofold higher than the maximum rate of brain acetate utilization (V(max)(util) = 0.50 +/- 0.08 micromol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2-3 mM. At such high plasma acetate concentration, the rate-limiting step for glial acetate metabolism is not the BBB, but occurs after entry of acetate into the brain.
Deelchand
Dinesh K
DK
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. dinesh@cmrr.umn.edu
Shestov
Alexander A
AA
Koski
Dee M
DM
Uğurbil
Kâmil
K
Henry
Pierre-Gilles
PG
D000085:Acetates / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000465:Algorithms; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D001711:Biotransformation; D001923:Brain Chemistry / Q000502:physiology*; D002952:Citric Acid Cycle / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007262:Infusions, Intravenous; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D000596:Amino Acids; D005973:Glutamine; D018698:Glutamic Acid; D011766:Pyruvate Carboxylase