COMT

Catechol-O-methyltransferase (COMT) is an enzyme that degrades catecholamines such as dopamine, epinephrine, and norepinephrine.

Norepinephrine degradation. Catechol-O-methyltransferase is shown in green boxes. Specific reactions catalyzed by COMT include: Dopamine → 3-Methoxytyramine DOPAC → HVA (homovanillic acid) Norepinephrine → Normetanephrine Epinephrine → Metanephrine Dihydroxyphenylethylene glycol (DOPEG) → Methoxyhydroxyphenylglycol (MOPEG) 3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid (VMA) Dopamine degradation. The COMT gene is located on human chromosome 22 where it codes for multiple proteins including a membrane-bound form (MB-COMT) and a soluble form (S-COMT) which are expressed in the brain. These proteins are involved in the termination of dopaminergic neurons in the prefrontal cortex.

The Val108/158Met polymorphism

In addition to coding for multiple isoforms, the COMT gene itself is also polymorphic. There is a common single nucleotide polymorphism (SNP) located on codon 108 of the soluble form and codon 158 of the membrane bound form (Val108/158Met). This polymorphism results in the substitution of Valine (Val) for Methionine (Met). Individuals who are homozygous for the Met allele exhibit preserved levels of dopamine compared to individuals who are homozygous for the Val allele.

Associations have been reported between the Val108/158Met polymorphism and performance on the Wisconsin Card Sorting Test (WCST) in healthy adults. Individuals who have more copies of the Met allele make fewer preservative errors on the Wisconsin Card Sorting Test but are more likely to suffer from borderline personality disorder. 9% of Kenyans, 31% of Caucasians and 27% of South-west Asians are homozygous for the Met allele.