Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier

J Biol Chem. 1996 Aug 9;271(32):19129-33. doi: 10.1074/jbc.271.32.19129.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Biological Transport
  • Blood-Brain Barrier*
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cattle
  • Cell Membrane / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Kinetics
  • Proline / analogs & derivatives*
  • Proline / physiology


  • Amino Acids
  • 4-ketoproline
  • Proline