Document Detail


The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport.
MedLine Citation:
PMID:  21501141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H(+) -coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (K(m) 1-10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid-based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (K(m) 0.1-0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high-affinity (K(m) 2-3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid-based drugs by mediating transport in both the small intestine and kidney.
Authors:
David T Thwaites; Catriona M H Anderson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  British journal of pharmacology     Volume:  164     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-03-19     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1802-16     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Epithelial Research Group, Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. d.t.thwaites@ncl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems / genetics,  metabolism*
Amino Acids / metabolism
Animals
Biological Transport
Humans
Intestine, Small / metabolism
Kidney / metabolism
Pharmaceutical Preparations / metabolism
Tissue Distribution
Grant Support
ID/Acronym/Agency:
078640/Z/05/Z//Wellcome Trust
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Amino Acids; 0/Pharmaceutical Preparations
Comments/Corrections

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