The activities of delta-aminolaevulinic acid synthase and haem synthase in experimental sideroblastic anaemia. Effect of mitochondrial iron excess on the enzyme activity in peripheral red blood cells.

Experimental sideroblastic anaemia was produced in normal and in iron loaded guinea pigs by intraperitoneal (i.p.) administration of isoniazid and cycloserine. Subsequently, the activities of delta-aminolaevulinic acid synthase (ALA-S) and of haem synthase in peripheral red blood cells were measured and in particular the relationships of enzyme activities to the iron status were examined. The ALA-S activity showed a similar decrease in all animals with sideroblastic anaemia. The haem synthase activity was increased probably due to secondary induction, but it was significantly less increased in animals with the highest values for iron status. This finding indicates that mitochondrial iron accumulation may have limited the compensatory increase of haem synthase activity. It is likely that also in human sideroblastic anaemia mitochondrial iron overload may have a secondary limiting effect on the haem synthase activity in erythroid cells.