Active involvement of catalase during hemolytic crises of favism

Abstract

The endemic occurrence of favism in certain Mediterranean regions provided an investigative opportunity for testing in vivo the validity of claims as to the role of catalase in protecting human erythrocytes against peroxidative injury. Reduced activity of catalase was found in the erythrocytes of six boys who were deficient in erythrocytic glucose- 6-phosphate dehydrogenase (G6PD) and who were studied while suffering hemolysis after ingesting fava beans. Activity of catalase was further reduced when their red blood cells were incubated with aminotriazole. In contrast, minimal reduction of catalase activity was found, both with and without incubation with aminotriazole, in erythrocytes of a G6PD-deficient boy who had ingested fava beans 7 days earlier and in erythrocytes of seven G6PD-deficient men with a past history of favism. These results confirmed earlier studies in vitro indicating that catalase is a major disposer of hydrogen peroxide in human erythrocytes and, like the glutathione peroxidase/reductase pathway, is dependent on the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The effect of divicine on purified catalase and on the catalase of intact G6PD-deficient erythrocytes was similar to the previously demonstrated effect on catalase of a known system for generating hydrogen peroxide. This effect of divicine strengthens earlier arguments that divicine is the toxic peroxidative component of fava beans.

Lipid peroxidation and antioxidant capacity of G6PD-deficient patients with A-(202G>A) mutation

“…Previous in vitro studies demonstrated the importance of NADPH in maintaining antioxidant enzymes, such as catalase (Scott et al, 1993). Gaetani et al (1996) reported a decrease in catalase levels and reduced glutathione in red blood cells with G6PD deficiency during hemolytic crises. Therefore, it was expected that erythrocyte with G6PD deficiency would show a greater susceptibility to damage caused by reactive oxygen species, since there would be less maintenance of NADPH-dependent enzymes, such as catalase and glutathione reductase in G6PDdeficient individuals without hemolytic crisis.…”

A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency

“…Glucose-6-phosphate dehydrogenase (G6PD, E.C. 1.1.1.49) is a metabolic enzyme that catalyzes the first and rate-limiting step of the pentose phosphate pathway, converting d -glucose-6-phosphate (G6P) to 6-phosphoglucono-δ-lactone and producing the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) [1] , which plays a critical role in protecting cells against oxidative stress by regulating the levels of reduced glutathione [2] . G6PD is particularly important in erythrocytes because it is the sole production source of reducing equivalents.…”

Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

“…The INS gene encodes insulin, which increases cell permeability to fatty acids and accelerates the pentose phosphate cycle for NADPH production in the liver ( 56 , 57 ). The CAT gene encodes catalase, a crucial scavenger of hydrogen peroxide in human erythrocytes, which is dependent on the availability of PPP-derived NADPH ( 58 ). NADPH is known to be tightly bound to mammalian catalase, and prevents inactivation of catalase by H 2 O 2 ( Fig.…”