Glutathione reductase deficiency

Glutathione reductase deficiency (OMIM 138300) is an autosomal disease and, except when very severe, is not associated with hemolysis. The disease has been associated with drug-sensitive hemolysis and favism. ... 

Loos et al. (L2) described a leukocytic glutathione reductase deficiency in three children of one family. The PMN glutathione-reductase activity was 10-15% of normal controls. 

Genetic Glucose-6-phosphate dehydrogenase deficiency, glutathione deficiency, glutathione reductase deficiency, thalassemia, tyrosinemia, Wilson s disease, 6-aminolevulinic acid dehydratase deficiency... 

An en2ymatic method for assessing riboflavin deficiency in humans has been developed (74). It is based on the fact that NADPH-dependent glutathione reductase of red cells reflects riboflavin fluctuations. 

Although riboflavin is fundamentally involved in metabolism, and deficiencies are found in most countries, it is not fatal as there is very efficient conservation of tissue riboflavin. Riboflavin deficiency is characterized by cheilosis, lingual desquamation and a seborrheic dermatitis. Riboflavin nutritional status is assessed by measurement of the activation of erythrocyte glutathione reductase by FAD added in vitro. 

Lll. Loos, H., Roos, D., Weening, R and Houwerzijl, J., Familial deficiency of glutathione reductase in human blood cells. Blood 48,53-62 (1976). GR4... 

Today, biochemical deficiency of riboflavin is accepted in the absence of clinical signs of deficiency. Biochemical signs of deficiency include change in the amount of the vitamin which is excreted in the urine, or change in the level of activity of a red blood cell (erythrocyte) enzyme, which is known as the erythrocyte glutathione reductase. Requirements for the vitamin are defined as that amount which will prevent both clinical and biochemical signs of deficiency. 

In pregnant women, there is a progressive increase in the erythrocyte glutathione reductase activation coefficient (an index of functional riboflavin nutritional status Section 7.5.2), which resolves on parturition despite the daily secretion of 200 to 400 /rg (0.5 to 1 /rmol) of riboflavin into milk. This suggests that the estrogen-induced riboflavin binding protein can sequester the vitamin for fetal uptake at the expense of causing functional deficiency in the mother. 

Tissue concentrations of flavin coenzymes in hypothyroid animals may be as low as in those fed a riboflavin-deficient diet, in hypothyroid patients, erythrocyte glutathione reductase (EGR) activity may be as low, and its activation by FAD added in vitro (Section 7.5.2) as high, as in riboflavin-deficient subjects. Tissue concentrations of flavin coenzymes and EGR are normalized by the administration of thyroid hormones, with no increase in riboflavin intake (Cimino et al., 1987). 

In addition to the role of flavoproteins in iron metabolism, it is possible that the anemia associated with riboflavin deficiency is a consequence of the impairment of vitamin Be metabolism in riboflavin deficiency. Pyridoxine oxidase is a flavoprotein and, like glutathione reductase, is very sensitive to riboflavin depletion (McCormick, 1989). Vitamin Be deficiency can result in hypochromic anemia as a result of impaired porphyrin synthesis. Although riboflavin depletion decreases the oxidation of dietary vitamin Be to pyridoxal (Section 9.2), it is not clear to what extent there is secondary vitamin Be deficiency in riboflavin deficiency This is partly because vitamin Be nutritional status is commonly... 

Glutathione reductase is especially sensitive to riboflavin depletion, in deficient animals, the activity of glutathione reductase responds earlier and more markedly than any other index of riboflavin stams apart from liver concentrations of flavin coenzymes and the activity of hepatic flavokinase (Prentice and Bates, 1981a, 1981b). The activity of the enzyme in erythrocytes can therefore be used as an index of riboflavin status. 

Like glutathione reductase, pyridoxine oxidase is sensitive to riboflavin depletion. In normal subjects and in experimental animals, the EGR and pyridoxine oxidase activation coefficients are correlated, and both reflect riboflavin nutritional status. In subjects with glucose 6-phosphate dehydrogenase deficiency, there is an apparent protection of EGR, so that even in riboflavin deficiency it does not lose its cofactor, and the EGR activation coefficient remains within the normal range. The mechanism of this protection is unknown. In such subjects, the erythrocyte pyridoxine oxidase activation coefficient gives a response that mirrors riboflavin nutritional status (Clements and Anderson, 1980). 

Dubick MA, Gretz D, and Majumdar AP (1995) Overt vitamin B-6 deficiency affects rat pancreatic digestive enzyme and glutathione reductase activities./oMrttfl/of Nutrition 125, 20-5. 

Prentice AM and Bates CJ (1981a) A biochemical evaluation of the erythrocyte glutathione reductase (EC 1.6.4.2) test for riboflavin status. 1. Rate and specificity of response in acute deficiency. British Journal of Nutrition 45,37-52. 

---