Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum glutathione reductase (NADPH-GSSG oxidoreductase, EC. 1.6.4.2 (GR)) has been examined in cystic fibrosis subjects (CF), obligate CF heterozygotes, and control subjects. Serum protein concentration was similar in the three groups. Regardless of the units used to express activity (milligrams of protein or milliters of serum) or whether or not samples were dialyzed against water or phosphate buffer, mean serum GR in CF was greater than in control subjects (P less than or equal to 0.002) in all series over several years. Under the above assay conditions no difference in serum GR between control subjects and carriers was detected. Calculated and assayed values of combined control and CF sera agreed as did expected and observed 50% activity in 1:2 sera dilutions in CF, control subjects, and carriers. Addition of FAD to incubation media did not effect enzyme activity in the three groups. Differences between CF and control subjects persisted after dialysis in membranes permitting passage of molecules of approximately 12,000 mol wt or less. These findings would tend to exclude the effect of extraneous serum factors in explaining the diffferences between CF and control subjects. The percentage of initial GR activity after four days storage (0-4 degrees) was significantly greater in CF than in control subjects (P less than 0.025). The effect of heparin on serum GR was recorded as the percentage of activity after incubation with heparin vs. activity in the standard assay for individual subjects. The effect of incubation with 5 mug/ml heparin on serum GR activity was greater in control subjects than in carriers (P less than 0.0005) and CF (P less than 0.0005). Mean serum GR activity in CF and carriers was unaffected by heparin, whereas mean activity in control subjects was decreased. In no control was the percentage of initial activity with heparin greater than the mean of CF and carrier groups. Only 3 of 20 CF and 4 of 20 carrier individuals had percentages lower than the control mean. The CF and carrier distributions were clearly different from the control distribution. Serum GR was determined in seven non-CF individuals with chronic obstructive pulmonary disease (COPD). Activity in the COPD was different from CF and no different from control subjects. In none of these controls or COPD was serum GR as great as the CF mean. Serum GR in no CF was as low as the mean of control subjects or COPD. It is concluded that serum GR activity is greater in CF than in control subjects, carriers, and non-CF COPD subjects; that the difference in activity is not attributable to an extraneous serum factor, that the activity difference is not secondary to chronic respiratory disease; that in comparison with control subjects, GR from CF serum behaves differently after storage; and that serum GR from CF and carriers behaves differently from control GR in the presence of heparin.
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PMID:Serum glutathione reductase and cystic fibrosis. 119 5

The quorum sensor and signalling molecule pyocyanin (PYO) contributes significantly to the pathophysiology of Pseudomonas aeruginosa infections. Comparison to phenothiazine drugs suggests that the antimalarial compound methylene blue (MB) can be regarded as a sulfur analog of PYO. This working hypothesis would explain why the synthetic drug MB behaves as a compound shaped in biological evolution. Here we report on redox-associated biological and biochemical properties of PYO in direct comparison to its synthetic analog MB. We quantitatively describe the reactivity of both compounds toward cellular reductants, the reactivity of their reduced leuco-forms towards O2, and their interactions with FAD-containing disulfide reductases. Furthermore, the interaction of PYO with human glutathione reductase was studied in structural detail by x-ray crystallography, showing that a single PYO molecule binds to the intersubunit cavity of the enzyme. Like MB, also PYO was also found to be active against blood schizonts of the malaria parasite P. falciparum in vitro. Furthermore, both compounds were active against the disease transmitting gametocyte forms of the parasites, which was systematically studied in vitro. As shown for mice, PYO is too toxic to be used as a drug. It may, however, have antimalarial activity in numerous human patients with concomitant Pseudomonas infections. MB, in contrast to PYO, is well tolerated and represents a promising agent for MB-based combination therapies against malaria. Current and future clinical studies can be guided by the comparisons between MB and PYO reported here. Additionally, it is of interest to study if and to what extent the protection from malaria in patients with cystic fibrosis or with severe wound infections is based on PYO produced by Pseudomonas species.
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PMID:The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. 2188 66