Document Detail

Substrate specificity of the amino acid transporter PAT1.
MedLine Citation:
PMID:  16699824     Owner:  NLM     Status:  MEDLINE    
The proton coupled amino acid transporter PAT1 expressed in intestine, brain, and other organs accepts L- and D-proline, glycine, and L-alanine but also pharmaceutically active amino acid derivatives such as 3-amino-1-propanesulfonic acid, L-azetidine-2-carboxylic acid, and cis-4-hydroxy-D-proline as substrates. We systematically analyzed the structural requirements for PAT1 substrates by testing 87 amino acids, proline homologs, indoles, and derivatives. Affinity data and effects on membrane potential were determined using Caco-2 cells. For aliphatic amino acids, a blocked carboxyl group, the distance between amino and carboxyl group, and the position of the hydroxyl group are affinity limiting factors. Methylation of the amino group enhances substrate affinity. Hetero atoms in the proline template are well tolerated. Aromatic alpha-amino acids display low affinity. PAT1 interacts strongly with heterocyclic aromatic acids containing an indole scaffold. The structural requirements of PAT1 substrates elucidated in this study will be useful for the development of prodrugs.
L Metzner; K Neubert; M Brandsch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-15
Journal Detail:
Title:  Amino acids     Volume:  31     ISSN:  0939-4451     ISO Abbreviation:  Amino Acids     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-14     Completed Date:  2007-10-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  111-7     Citation Subset:  IM    
Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
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MeSH Terms
Amino Acid Transport Systems / drug effects,  metabolism*
Caco-2 Cells
Membrane Potentials
Substrate Specificity
Symporters / drug effects,  metabolism*
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/SLC36A1 protein, human; 0/Symporters

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