Defective molecular variants of glucose-6-phosphate dehydrogenase and methaemoglobin reductase.

Unlike any other living cell, the mature erythrocyte is unable to divide and synthesize proteins. It must therefore sustain a relatively long life (about 100 days) without renewing its stock of enzymes. If this stock is genetically altered the red cell will be more likely than any other to suffer. Also the metabolic pathways are greatly simplified in the red cell as its essential metabolites are derived only from anaerobic glycolysis. Therefore it is not surprising that about a dozen genetically determined enzyme defects have already been identified in this cell. Of these two are selected for discussion: glucose-6-phosphate dehydrogenase (G6PD) deficiency, which alters the cell viability, and methaemoglobin reductase deficiency, which impairs its function. In both examples, it can be demonstrated that the basic defect is a structural modification of the enzyme molecule. The phenotypic consequence of the genetic lesion-probably a point mutation in most cases-is the production of an abnormal allele which decreases catalytic capability and/or in vivo stability.