Catechol-O-methyltransferase: Thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity

Low catechol-O-methyltransferase (COMT) activity (<8 units per milliliter) in the human erythrocyte is inherited as an autosomal recessive trait (COMT^L). The average half-life of COMT in erythrocyte lysates incubated at 48°C was significantly shorter in lysates from three subjects with low enzyme activity than in lysates from three subjects with high enzyme activity (12.5±0.9 minutes compared with 21.2±1.4 minutes, P<.01). When the ratios of COMT activities in lysates heated at 48°C for 15 minutes to enzyme activities in unheated samples were used as a measure of enzyme thermostability in blood samples from 316 randomly selected subjects, the ratios were significantly less for subjects with low enzyme activity than for subjects with higher enzyme activity. The presence of thermolabile COMT in blood of individuals homozygous for COMT^L raises the possibility that the locus COMT may represent the structural gene for the human enzyme.