Alanine metabolism, transport, and cycling in the brain.
Article Details
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Broer S, Broer A, Hansen JT, Bubb WA, Balcar VJ, Nasrallah FA, Garner B, Rae C
Alanine metabolism, transport, and cycling in the brain.
J Neurochem. 2007 Sep;102(6):1758-70. Epub 2007 May 14.
- PubMed ID
- 17504263 [ View in PubMed]
- Abstract
Brain glutamate/glutamine cycling is incomplete without return of ammonia to glial cells. Previous studies suggest that alanine is an important carrier for ammonia transfer. In this study, we investigated alanine transport and metabolism in Guinea pig brain cortical tissue slices and prisms, in primary cultures of neurons and astrocytes, and in synaptosomes. Alanine uptake into astrocytes was largely mediated by system L isoform LAT2, whereas alanine uptake into neurons was mediated by Na(+)-dependent transporters with properties similar to system B(0) isoform B(0)AT2. To investigate the role of alanine transport in metabolism, its uptake was inhibited in cortical tissue slices under depolarizing conditions using the system L transport inhibitors 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and cycloleucine (1-aminocyclopentanecarboxylic acid; cLeu). The results indicated that alanine cycling occurs subsequent to glutamate/glutamine cycling and that a significant proportion of cycling occurs via amino acid transport system L. Our results show that system L isoform LAT2 is critical for alanine uptake into astrocytes. However, alanine does not provide any significant carbon for energy or neurotransmitter metabolism under the conditions studied.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Alanine Large neutral amino acids transporter small subunit 2 Protein Humans UnknownNot Available Details - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions L-Glutamine Large neutral amino acids transporter small subunit 2 Protein Humans UnknownSubstrateDetails