Serum glutathione reductase and cystic fibrosis.

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 milliliters 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 differences 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. 