Biochemical Studies of Erythrocytes in a Patient with Pyroglutamic Acidemia (5-Oxoprolinemia)

Abstract An adult with pyroglutamic acidemia was investigated biochemically in efforts to explain his overproduction of pyroglutamate and his neurologic disease. The patient's erythrocytes contained no detectable glutathione, and their glutathione synthetase activity was less than 2 per cent of normal. These cells were loaded with free amino acids, most of them in concentrations five to 100 times normal. The erythrocytes also contained the unusual compound methionine sulfoxide. In skeletal muscle, in which glutathione was only reduced to 3 per cent of normal, there was no amino acid accumulation. The patient's overproduction of pyroglutamate is probably caused by increased in vivo activity of γ-glutamyl-cysteine synthetase due to absence of normal feedback inhibition by glutathione, with a resulting abundance of substrates available for γ-glutamyl cyclotransferase. Although lack of glutathione is apparently tolerable in short-lived erythrocytes, it could be disastrous in non-renewable neurons. Glutathione...

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