Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-6-8
pubmed:abstractText
The role of organic anion transporters in the mitochondrial uptake of glutathione (GSH) was investigated by assessing competition with substrates or inhibition with inhibitors of specific carriers and modulation of mitochondrial energetics. Potential artifacts in the transport methodology, including contamination of matrix space with extramitochondrial fluid, changes in matrix volume during incubations, efflux of transported GSH during sample processing, induction of the membrane permeability transition, contamination of the mitochondrial preparation with plasma membranes and GSH degradation, were corrected or eliminated. Substrates (i.e., malate, succinate) and an inhibitor (i.e., butylmalonate) of the dicarboxylate carrier, an inhibitor (i.e., phenylsuccinate) of the 2-oxoglutarate carrier, and glutamate produced significant inhibition of GSH uptake whereas substrates and inhibitors of the mono- and tricarboxylate carriers were generally without effect. Phosphoenolpyruvate, which is a substrate for the tricarboxylate carrier, inhibited GSH uptake, but this was due to induction of the membrane permeability transition and not to competition for uptake. Although glutamate inhibited GSH uptake, the converse did not occur. GSH uptake was pH-independent and aspartate had no effect, which suggest that the glutamate and glutamate-aspartate carriers are not involved in GSH uptake but that the glutamyl residue of GSH may be important in its transport. GSH uptake was dependent on phosphate and ATP generation. Hence, we conclude that both the dicarboxylate and 2-oxoglutarate carriers of the inner membrane can catalyze uptake of GSH into the matrix. The function of an additional, novel transporter cannot be excluded at present. This is the first study to define the function of mitochondrial anion carriers in GSH transport.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
608-18
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9580605-Adenosine Triphosphate, pubmed-meshheading:9580605-Animals, pubmed-meshheading:9580605-Antimycin A, pubmed-meshheading:9580605-Biological Transport, pubmed-meshheading:9580605-Carrier Proteins, pubmed-meshheading:9580605-Dicarboxylic Acid Transporters, pubmed-meshheading:9580605-Glutamic Acid, pubmed-meshheading:9580605-Glutathione, pubmed-meshheading:9580605-Hydrogen-Ion Concentration, pubmed-meshheading:9580605-Intracellular Membranes, pubmed-meshheading:9580605-Male, pubmed-meshheading:9580605-Membrane Transport Proteins, pubmed-meshheading:9580605-Mitochondria, pubmed-meshheading:9580605-Oxygen Consumption, pubmed-meshheading:9580605-Permeability, pubmed-meshheading:9580605-Rats, pubmed-meshheading:9580605-Rats, Inbred F344, pubmed-meshheading:9580605-Substrate Specificity
pubmed:year
1998
pubmed:articleTitle
Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers.
pubmed:affiliation
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.