gamma-Glutamyl amino acids. Transport and conversion to 5-oxoproline in the kidney
Transport of gamma-glutamyl amino acids, a step in the proposed glutathione-gamma-glutamyl transpeptidase-mediated amino acid transport pathway, was examined in mouse kidney. The transport of gamma-glutamyl amino acids was demonstrated in vitro in studies on kidney slices. Transport was followed by measuring uptake of /sup 35/S after incubation of the slices in media containing gamma-glutamyl methionine (/sup 35/S)sulfone. The experimental complication associated with extracellular conversion of the gamma-glutamyl amino acid to amino acid and uptake of the latter by slices was overcome by using 5-oxoproline formation (catalyzed by intracellular gamma-glutamyl-cyclotransferase) as an indicator of gamma-glutamyl amino acid transport. This method was also successfully applied to studies on transport of gamma-glutamyl amino acids in vivo. Transport of gamma-glutamyl amino acids in vitro and in vivo is inhibited by several inhibitors of gamma-glutamyl transpeptidase and also by high extracellular levels of glutathione. This seems to explain urinary excretion of gamma-glutamylcystine by humans with gamma-glutamyl transpeptidase deficiency and by mice treated with inhibitors of this enzyme. Mice depleted of glutathione by treatment with buthionine sulfoximine (which inhibits glutathione synthesis) or by treatment with 2,6-dimethyl-2,5-heptadiene-4-one (which effectively interacts with tissue glutathione) exhibited significantly less transport of gamma-glutamyl amino acids than did untreated controls. The findings suggest that intracellular glutathione functions in transport of gamma-glutamyl amino acids. Evidence was also obtained for transport of gamma-glutamyl gamma-glutamylphenylalanine into kidney slices.
- OSTI ID:
- 6380874
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 12
- Country of Publication:
- United States
- Language:
- English
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AMINO ACIDS
MEMBRANE TRANSPORT
ALANINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
CYSTINE
ENZYME INHIBITORS
GLUTATHIONE
IN VITRO
KIDNEYS
METHIONINE
MICE
PEPTIDE HYDROLASES
PROLINE
STRUCTURE-ACTIVITY RELATIONSHIPS
SULFONES
SULFUR 35
TRACER TECHNIQUES
AMINES
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DISULFIDES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
PYRROLES
PYRROLIDINES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
SULFUR ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques