THERMOLABILE 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE AS A CAUSE OF MILD HYPERHOMOCYSTEINEMIA

Thermolability of 5,10-methylenetetrahydrofolate reductase (MTHFR) was examined as a possible cause of mild hyperhomocysteinemia in patients with premature vascular disease. Control subjects and vascular patien ts with mild hyperhomocysteinemia and with normohomocysteinemia were s tudied. The mean (+/-SD) specific MTHFR activity in lymphocytes of 22 control subjects was 15.6 (+/-4.7) nmol CH2O/mg protein/h (range: 9.1- 26.6), and the residual activity (+/-SD) after heat inactivation for 5 min at 46 degrees C was 55.3 (+/-12.0)% (range: 35.9-78.3). By measur ement of MTHFR activity, two distinct subgroups of hyperhomocysteinemi c patients became evident. One group (n = 11) had thermolabile MTHFR w ith a mean (+/-SD) specific activity of 8.7 (+/-2.1) nmol CH2O/mg prot ein/h (range: 5.5-12.7) and a residual activity, after heat inactivati on, ranging from 0% to 33%. The other group (n = 28) had normal specif ic activity (+/-SD) of 21.5 (+/-7.2) nmol CH2O/mg protein/h (range: 10 .0-39.0) and a normal residual activity (+/-SD) of 53.8 (+/-9.2)% (ran ge: 33.1-71.5) after heat inactivation. The mean (+/-SD) specific acti vity of 29 normohomocysteinemic patients was 20.7 (+/-6.5) nmol CH2O/m g protein/h (range: 9.4-33.8), and the mean (+/-SD) residual activity after heat inactivation was 58.2 (+/-10.2)% (range: 43.0-82.0). Thus, in 28% of the hyperhomocysteinemic patients with premature vascular di sease, abnormal homocysteine metabolism could be attributed to thermol abile MTHFR.