title: Red cell glutathione deficiency: clinical and biochemical investigations using sheep as an experimental model system.
abstract: The biochemical properties of red cells from normal sheep and sheep with three types of red cell glutathione (GSH)-deficiency were compared. One deficiency was due to an impaired transport system for amino acids (lesion 1), one was the result of a diminished activity of gamma-glutamyl cysteine synthetase (GC-S) (lesion 2) and the third was a combined deficiency produced by selective breeding to give animals with both lesions 1 and 2. Under normal husbandry conditions no clinical symptoms were apparent in sheep with lesion 2, but red cells from sheep with lesion 1 and lesions 1 + 2 showed an increased osmotic fragility, a greater tendency to form Heinz bodies and a shorter potential life span than normal. These deficiencies were not found in tissues other than blood. Normal and GSH-deficient red cells had the expected low concentrations of 5-oxoproline. The effects of the toxic agents phenylhydrazine, s-methylcysteine sulphoxide and nitrite in vivo were measured in sheep of the different types. GSH-deficient sheep responded earlier and more dramatically than normal sheep, showing greater methaemoglobin formation, and for phenylhydrazine and s-methylcysteine sulphoxide, more severe anaemia. Sheep with the combined lesions were in general the most susceptible, but even they had the ability to recover from moderately severe oxidative challenge.
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000097:blood; D005978:Glutathione / Q000097:blood / Q000172:deficiency*; D009573:Nitrites / Q000633:toxicity; D010659:Phenylhydrazines / Q000633:toxicity; D011761:Pyrrolidonecarboxylic Acid / Q000097:blood; D012756:Sheep; D013454:Sulfoxides / Q000633:toxicity
chemical_list: D009573:Nitrites; D010659:Phenylhydrazines; D013454:Sulfoxides; C008389:methiin; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003545:Cysteine; D011761:Pyrrolidonecarboxylic Acid