Glutathione reductase coenzyme

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

Perham, R. N., Scrutton, N.S. Berry, A. (1991)- New enzymes for old redesigning the coenzyme and substrate specificities of glutathione reductase. Bioessays, 13, 515-25. 

How the stereospecificity arises (a) Reactions involving flavin coenzymes (i) Glutathione reductase (EC 1.6.4.2)... 

Glutathione reductase amino acid composition, 102,104,105 cystine residues, 104 kinetic studies, 138-141 mechanism, 94, 97-98,134 metabolic functions, 129-133 reaction catalyzed, 92 reduction of, 112, 113 specificity of, 92-93 coenzymes and, 94 thiol groups, 141-142 two-electron-reduced enzyme, properties, 133-138... 

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). 

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. 

Fig. 10. Hydrogen donor systems for ribonucleotide reduction. Enzyme reactions are I thioredoxin reductase (EC 1.6.4.5) II ribonucleotide reductase (EC 1.17.4) III glutathione reductase (EC 1.6.4.2). GSH, GSSG reduced and oxidized glutathione NADPH, NADP reduced and oxidized nicotinamide adenine dinucleotide phosphate coenzymes. The hydrogen transfer chain is continued in Fig. II...

The coenzyme activity of Alg-NADP was determined enzymatically by the glutathione reductase system (38). The assay mixture consisted of 250 pmol Tris-HCl buffer (pH 8.0), 2.7 [xmol EDTA, 13.2 pmol GSSG, an appropriate amount of Alg-NADP", and 20 units of GR in a total volume of 2.87 ml. The reaction was started by the addition of the enzyme and the reaction mixture was incubated at 30°C. Absorbance at 340 nm was measured with a double beam spectrophotometer. The reference contained all components except for Alg-NADP. In the calculation of the amount of Alg-NADPH produced, a molar absorption coefficient for NADPH of 6.22 X 10 l-mol -cm was used. 

As mentioned earlier, nearly all tissues require riboflavin. The free vitamin is trapped as one of its phosphorylated coenzyme forms, which then become specifically associated (and in a few cases covalently linked) to the protein chains of catalytic flavoenzymes. If not already covalently linked, the flavin coenzyme can often be liberated by extremes of pH or by other nonphysiological maneuvers. In a few biological locations, such as the mature red cell, flavoenzymes such as glutathione reductase (NADPH oxidized glutathione oxidoreductase EC 1.6.4.2) may exist partly in their apoenzyme form, i.e., without the flavin coenzyme and therefore without enzyme activity. An increased supply of riboflavin will permit the depleted coenzyme (in this case FAD) to be synthesized so that enzyme activity can be restored. 

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