Role of pentose-phosphate pathway in haemolytic crisis of chronic copper toxicity of sheep.

Although the rise in blood copper is associated with onset of the acute haemolytic crisis of chronic copper poisoning in sheep, the sudden fall in erythrocyte glutathione is apparently not due to a direct action of the copper. Moreover the reduced glutathione of the red cells is converted to some form that is not capable of regeneration by the pentose-phosphate mechanism. Only negligible inhibition of the pentose-phosphate enzymes occurs. As the haemolysis proceeds, there is a rapid recovery of erythrocyte glutathione levels, and a marked increase in pentose-phosphate enzyme activity, consistent with influx of young red cells. It seems that the release of copper into blood from liver at the haemolytic crisis is associated with an increase of the oxidative state of the blood, possibly by simultaneous release of other components from the liver.