Question

Briefly describe the role of MAO-B, COMT, DAT, and L-DOPA in the synthesis and metabolism of dopamine.

Answer 1

Dopamine is a catecholamine synthesized from the amino acid tyrosine in the brain. Tyrosine is metabolized to dihydroxyphenylalanine DOPA) by the enzyme tyrosine hydroxylase and then DOPA is metabolized to dopamine via aromatic amino acid decarboxylase. Dopamine is mainly metabolized by MAO-B and COMT. Therefore, inhibition of tyrosine hydroxylase or decarboxylase or both of these enzymes would decrease dopamine metabolism and result in increased levels of dopamine in the brain MAO-B present in glial cells and involved in inactivation of dopamine, epinephrine and nor epinephrine and cellular degeneration by producing hydrogen peroxides that are converted by iron to highly toxic oxygen free radicals and leads to cell death. COMT (Cathecol O methyl transferase) is located intracellularly in the central nervous system (CNS). COMT are the enzymes which inactivates the dopamine, epinephrine and nor epinephrine by introducing a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM) DAT (Dopamine transporter) transports the dopamine and plays an important role in extracellular dopamine homeostasis LDOPA (L-3, 4-dihydroxyphenylalanine) is produced from the amino acid L-tyrosine by the enzyme tyrosine hydroxylase. It is also the precursor for catecholamine neurotransmitters dopamine, nor epinephrine and epinephrine. Dopamine is formed by the decarboxylation of L- DOPA. L DOPA is a precursor for the pigment melanin (coloring pigment of the skin)