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1 Department of Physiology and Biophysics, Rosalind Franklin University School of Medicine and Science, The Chicago Medical School, North Chicago, IL, USA
2 Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain
3 Department of Neural and Behavioral Science, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA, USA
* To whom correspondence should be addressed. E-mail: Richard.Hawkinsr{at}rosalindfranklin.edu.
Four Na+-dependent transporters of neutral amino acids (NAA) are known to exist in the abluminal membranes (brain side) of the blood-brain barrier (BBB). This article describes the kinetic characteristics of systems A, ASC and N that together with the recently described Na+-dependent system for large NAA (Na+- LNAA) provide a basis to understand the functional organization of the BBB. The data demonstrate that system A is voltage dependent (3 positive charges accompany each molecule of substrate). Systems ASC and N are not voltage dependent. Each NAA is a putative substrate for at least one system, and several NAA are transported by as many as three. System A transports: Pro, Ala, His, Asn, Ser and Gln; system ASC transports Ser, Gly, Met, Val, Leu, Ile, Cys and Thr; system N transports Gln, His, Ser and Asn; Na+-LNAA transports Leu, Ile, Val, Trp, Tyr, Phe, Met, Ala, His, Thr, and Gly. Together these four systems have the capability to actively transfer every naturally occurring NAA from the ECF to endothelial cells and thence to the circulation. The existence of facilitative transport for NAA (L1) on both membranes provides the brain access to essential NAA. The presence of Na+-dependent carriers on the abluminal membrane provide a mechanism by which NAA concentrations in the extracellular fluid of brain are maintained at about 10% those of the plasma.
This article has been cited by other articles:
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  R. L. O'Kane, J. R. Vina, I. Simpson, R. Zaragoza, A. Mokashi, and R. A. Hawkins Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+ Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E412 - E419. [Abstract] [Full Text] [PDF]
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 R. A. Hawkins, R. L. O'Kane, I. A. Simpson, and J. R. Vina Structure of the Blood-Brain Barrier and Its Role in the Transport of Amino Acids J. Nutr., January 1, 2006; 136(1): 218S - 226S. [Abstract] [Full Text] [PDF]
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