Remarques sur les enzymopathies génétiques du globule rouge

Abstract

Summary The mature red cell has lost all capability to divide and to synthetize proteins. It is therefore more exposed than any other cells to suffer from genetically determined enzyme defects. A good number of these have now been identified in the red cell. Only those which impair the erythrocyte viability or function will be considered and their contribution to molecular pathology be discussed. o 1) The intrinsic nature of the defect, i. e. a qualitative abnormality of the enzyme molecule, has been approached in several enzyme defects, such as glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase and NADH diaphorase deficiency. In some cases, the qualitative abnormality may also have a quantitative effect. 2) The consequence of the enzyme defects on the red cell metabolism is susprisingly poorly understood. If the correlation between the lack of methemoglobin reductase and methemoglobinemia is easy to assume, no ready explanation can be given to the drug-induced hemolysis associated to the enzyme defects involving NADPH-production and/or glutathione metabolism, nor to the chronic shortage of the red cell life span seen in defects of glycolytic enzymes. Knowing the defective enzyme does not provide an immediate clue to the mechanism of the disorder. 3) The extension of the enzyme defect to other blood cells or tissues is variable. In some cases the defect is not shared by the white blood cells (G6PD A-, pyruvate kinase, « regularNADH-diaphorase deficiency, PGM1 deficiency). Sometimes it can be detected in other cells, without extra-hematological signs (G6PD B-, phosphohexose isomerase). At last it can be present in other tissues and give rise to a generalized disease (triose phosphate isomerase deficiency, phosphoglycerate kinase, NADH-diaphorase deficiency with mental retardation). These differences are due to separate genetic control of the enzyme in the red cell (pyruvate kinase), or more often to differences of the in vivo instability of the abnormal enzyme molecule (G6PD, NADH-diaphorase). In this respect the red cell represents a unique tool for investigating molecular ageing of enzymes in eukaryotes.