The human body relies on enzymes like Catechol-O-methyltransferase (COMT) to maintain proper function. COMT helps break down chemical messengers in the body, including those in the brain.
A common genetic variation, Val158Met, alters COMT’s efficiency. This slight difference in the COMT gene sequence is a normal part of human diversity and can subtly influence brain function.
The COMT Enzyme’s Core Function
The primary role of the COMT enzyme involves the breakdown of a group of neurotransmitters known as catecholamines. These include dopamine, norepinephrine, and epinephrine, which are chemical messengers that transmit signals between nerve cells throughout the body and brain. COMT acts by adding a methyl group to these compounds, effectively deactivating them.
This enzymatic activity helps regulate the levels of these neurotransmitters in various tissues. COMT is active in several parts of the body, including the brain, liver, and kidneys. In the brain, its function is particularly relevant for maintaining appropriate levels of dopamine in specific regions.
COMT’s breakdown process prevents excessive catecholamine accumulation, which could overstimulate neural pathways. By regulating these neurotransmitter levels, COMT helps ensure the nervous system operates within a balanced range and contributes to the orderly flow of information in the brain.
Understanding the Val and Met Variations
The Val158Met polymorphism is a common genetic change in the COMT gene that results in two distinct versions of the enzyme. At position 158 in the enzyme’s protein structure, individuals can have either the amino acid valine (Val) or methionine (Met). This seemingly small difference leads to a significant change in how quickly the COMT enzyme works.
The Val version of the enzyme is more stable at body temperature and has higher enzymatic activity, meaning it breaks down catecholamines at a faster rate. In contrast, the Met version is less stable and exhibits lower enzymatic activity, leading to a slower breakdown of these neurotransmitters. Individuals inherit two copies of each gene, one from each parent, resulting in three possible genetic combinations for COMT Val158Met.
These combinations are Val/Val, Met/Met, and Val/Met. Individuals with the Val/Val genotype possess two copies of the high-activity version of the enzyme, leading to the fastest breakdown of catecholamines. Those with the Met/Met genotype have two copies of the low-activity version, resulting in the slowest breakdown. Individuals with the Val/Met genotype have one copy of each version, leading to an intermediate level of COMT activity.
How COMT Val158Met Influences Brain Function
The differing COMT enzyme activities stemming from the Val158Met variations can influence brain chemistry, particularly dopamine levels in the prefrontal cortex. This brain region is involved in executive functions, which include planning, decision-making, working memory, and attention. The Met version, with its slower dopamine breakdown, tends to result in higher dopamine levels in this area.
For cognitive function, a “Goldilocks” principle applies to dopamine levels. Both too little and too much dopamine can impair performance in prefrontal cortex-dependent tasks. Individuals with the Met/Met genotype, having higher prefrontal dopamine, may show advantages in certain cognitive tasks. Conversely, those with the Val/Val genotype, with lower prefrontal dopamine, perform differently.
The COMT Val158Met polymorphism also affects an individual’s response to stress. Higher prefrontal dopamine levels, linked to the Met allele, are associated with a more efficient coping mechanism. Optimal dopamine signaling in the prefrontal cortex helps regulate physiological and psychological responses to challenging situations. The Val allele, leading to lower dopamine, is associated with different stress reactivity patterns.
Variations in COMT activity influence emotional processing and stability. While precise mechanisms are complex, the enzyme’s influence on dopamine and norepinephrine levels affects neural circuits involved in reward, motivation, and emotional resilience. COMT genotypes are associated with variations in mood and emotional experiences.