Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier.
Regulation of neutral amino acid transport was studied using isolated plasma membrane vesicles derived from the bovine blood-brain barrier. Neutral amino acids cross the blood-brain barrier by facilitative transport system L1, which may allow both desirable and undesirable amino acids to enter the brain. The sodium-dependent amino acid systems A and Bo,+ are located exclusively on abluminal membranes, in a position to pump unwanted amino acids out. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle, is an integral protein of the luminal membrane of the blood-brain barrier. We demonstrate that oxoproline, an intracellular product of the gamma-glutamyl cycle, stimulates the sodium-dependent systems A and Bo,+ by 70 and 20%, respectively. Study of system A showed that 2 mM oxoproline increased the affinity for its specific substrate N-methylaminoisobutyrate by 50%. This relationship between the activity of the gamma-glutamyl cycle and system A transport may provide a short term regulatory mechanism by which the entry of potentially deleterious amino acids (i.e. neurotransmitters or their precursors) may be retarded and their removal from brain accelerated.
Lee
W J
WJ
Department of Physiology and Biophysics, Finch University of Health Science/The Chicago Medical School, North Chicago, Illinois 60064-3095, USA.
Hawkins
R A
RA
Peterson
D R
DR
Viña
J R
JR
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D011392:Proline / Q000031:analogs & derivatives* / Q000502:physiology
D000596:Amino Acids; C036784:4-ketoproline; D011392:Proline