Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2

Eur J Pharm Sci. 2008 Oct 2;35(3):161-74. doi: 10.1016/j.ejps.2008.06.015. Epub 2008 Jul 5.

Abstract

LAT1 and LAT2 are heterodimeric large amino acid transporters that are expressed in various tissues, including the intestinal wall, blood-brain barrier, and kidney. These transporters consist of membrane spanning light chain and heavy chain, and they act as 1:1 exchangers in concert with other amino acid transporters. Only a few drugs (less than 10) are substrates of LAT1 and LAT2, including L-DOPA, alpha-methyldopa, melphalan, and gabapentin. The mechanisms and substrates have been mostly elucidated using mammalian cells and Xenopus oocytes. The in vivo relevance of LAT1 and LAT2 in pharmacokinetics is obscure, because contradictory findings have been reported. It is difficult to make quantitative pharmacokinetic conclusions about LAT1 and LAT2. This is due to the possible involvement of other transporters (including cross-linked heterodimers of light chain with different heavy chains, other overlapping transporters, for example TAT1), competing endogenous amino acids, and saturation phenomena. This review presents the current functional knowledge on LAT1 and LAT2 with emphasis on their potential involvement in pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Amino Acid Transport System y+ / chemistry
  • Amino Acid Transport System y+ / classification
  • Amino Acid Transport System y+ / metabolism*
  • Animals
  • Biological Transport
  • Fusion Regulatory Protein 1, Light Chains / chemistry
  • Fusion Regulatory Protein 1, Light Chains / classification
  • Fusion Regulatory Protein 1, Light Chains / metabolism*
  • Humans
  • Kinetics
  • Large Neutral Amino Acid-Transporter 1 / chemistry
  • Large Neutral Amino Acid-Transporter 1 / classification
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Models, Biological
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Protein Conformation

Substances

  • Amino Acid Transport System y+
  • Fusion Regulatory Protein 1, Light Chains
  • Large Neutral Amino Acid-Transporter 1
  • Pharmaceutical Preparations
  • SLC7A8 protein, human