Question

Describe the pharmacological importance of the enzymes COMT, and MAO.

Answer 1

COMT stands for Catechol-O-methyltransferase and MAO stands for Monoamine oxidase

COMT: This enzyme incorporates methyl group in the catecholamine family of neurotransmitters. Catecholamines are a group of neurotransmitters and chemically have single amino group along with catechol ring. These are the synthesized from phenylalanine or tyrosine amino acids and function in transmission of nerve impulse across synapse. Some examples are Dopamine, Adrenaline, Noradrenaline etc. The enzyme COMT is involved in degradation of catecholamines by introducing methyl group in its structure and thus causing their inactivation.

Reaction catalyzed by COMT

MAO enzyme is also involved in damaging these catecholamines but its reaction involves the use of oxygen to remove the amino group of the catecholamine to form ketone derivative and hence inactivating the neurotransmitter.

Reaction catalyzed by MAO

The pharmacological importance of these enzyme lie in the fact that as soon as a neurotransmitter reaches the post synaptic receptor, it should be degraded or inactivated so as to prevent the repeated stimulation and hence excess of action potential in the post synaptic neuron which can even lead to permanent damaging of the neuron. These enzymes thus prevent this by destroying the neurotransmitter. The patients suffering from Schizophrenia are known to have high level of dopamine in their systems and it is expected that the improper functioning of these two enzymes or some problem in the gene responsible of these.

Another importance of these enzymes is their involvement in treating diseases caused due to low level of neurotransmitters. Inhibiting this enzyme can help curing diseases like Parkinson's. In this disease the dopamine producing cells have either died or are less active. So, the dopamine levels in these patients are low and so they are not able to regulate their movements. When the medicines containing Dopamine or its precursor are given to them, these are substrates for COMT and MAO enzymes which degrade them and the action of medicine is decreased. To increase the efficiency of such medicines, COMT and MAO inhibitors are given so as to inactivate the enzyme and hence improve the condition of patients by making required amount of catecholamine neurotransmitters available for action. Similar is the case with those suffering from Alzheimer’s disease and hence require the inhibitors of these enzymes to cure the symptoms of the disease.