Demonstration of an enzyme variant in a case of congenital methaemoglobinaemia.
Authors: C A West, B D Gomperts, E R Huehns, I Kessel, J R Ashby
Journal: BMJ (1967)

Serum yG-globulins-Tee and Watkins BRITrIS The experiments reported in this paper, conducted over a period of nine weeks, indicate that different electrophoretic fractions of yG-globulin possess different breakdown rates; the observed half-life of the entire yG-globulin preparation being a mean of the individual values.The overall breakdown rate is non-linear and the half-life values increase with time.However, mean half-life values measured over the nine-week period were 25 days (J.W.) and 18 days (patient) respectively.These half-life values are in good agreement with those of Cohen and Freeman (1960), who reported half-life values of 21-26 days for yG-globulins in the normal individual.The half-life values obtained from the present experiment appeared to be characteristic of the catabolism of the individual and to be independent of the source of the labelled yG- globulin.The difference in the half-life values found for yG-globulins in J. W. and the patient cannot be attributed to concentration dependence of yG-globulin catabolism, since it was found that their serum yG-globulin levels were 838 and 940 mg./100 ml.respectively.However, starch-gel electrophoresis experiments showed that in the patient the serum Y2'Y1 ratio was approxi- mately 2: 1, as compared with 1: 1 in J. W. The 2: 1 y-globulin ratio would be expected to predispose the overall yG-globulin catabolic rate in the cancer patient to be faster than that in the control subject with a 1: 1 ratio, since it has been shown (Fig. 2) that the Y2 fraction is broken down faster than the Yi fraction.The possibility that the catabolic rates are affected by allo- typic differences between the donor yG-globulins and those of the recipient cannot be overlooked.The patient had had several transfusions during the course of operations for removal of his neoplasms.However, J. W. carried out a similar experi- ment to that reported in this paper on himself a year previously using homologous yG-globulin from a normal individual.Two yG-globulin preparations were used for this particular experiment.One was obtained from the normal donor directly and labelled with 1251, the other was obtained from this donor after a "booster" injection of tetanus toxoid and labelled with 131I.Both labelled yG-globulin preparations showed the same heterogeneous breakdown pattern over a period of 15 weeks.The apparent biological half-life values were identical to those reported for J. W. in this paper.The results of this experiment (Watkins and Tee, 1966), together with the present observations, indicate that the observed catabolic phenomena are not artifacts produced by immune response to the injected homologous yG-globulin.This work is now being extended to study the catabolism of yG-globulins in other subjects,.including both normal volunteers and patients with various pathological conditions. SummaryThe survival of radioiodine-labelled serum yG-globulins was determined in a normal volunteer and in a cancer patient over a period of nine weeks.It was found that different electrophoretic fractions of the yG-globulin broke down at different rates.This catabolic heterogeneity of the yG-globulins gave rise to an apparent time dependence of the observed half-life value.Mean halflife values, as measured over the entire nine-week period, were 25 days for yG-globulins in the normal volunteer and 18 days for the same yG-globulin preparation in the cancer patient.The breakdown rates in both individuals appeared to be independent of the source of the labelled yG-globulins.