Leukocyte methylmalonyl-CoA mutase. I. Vitamin B12 deficiency

Abstract

The leukocyte activity of the 5’ deoxyadenosyl B12-linked enzyme, methylmalonyl-CoA mutase, was measured in vitro in seven patients with vitamin B12 deficiency (group I), six patients with anemia not due to vitamin B12 lack (group II), and nine normal healthy adult controls (group III). Assay was based on the rate of utilization of enzymatically prepared, chromatographically purified 14C carboxy-labeled racemic methylmalonyl-CoA. The time course of the assay as described was linear over a 1-hr period at activities of 0.013 to 0.34 nmole/hr of methylmalonyl-CoA utilized. Leukocyte mutase activities were measured without (basal) and with added dAB12. Mutase activities were: group I basal, mean 0.034 (0.005 to 0.099); group II, mean 0.114 (0.017 to 0.309); group III, mean 0.286 ± 0.079 (0.170 to 0.459) nmole/mg leukocyte protein per hr. In the presence of added dAB12 (100 to 500 ng) activities were: group I, 0.091 (0.018 to 0.190), group II, 0.093 (0.005 to 0.308), and group III, 0.232 ± 0.135 (0.090 to 0.510) nmole/mg leukocyte protein per hr. All seven vitamin B12-deficient subjects showed enhanced leukocyte methylmalonyl-CoA mutase activity in the presence of added dAB12. No correlation was apparent between leukocyte mutase ativities of the vitamin B12-deficient subjects and the excretion of urinary methylmalonate, the severity of the anemia, or the presence of neurological impairment of the vitamin B12-deficiency state.