Dopamine Metabolism

Dopamine is a neurotransmitter used in many brain circuits.

Dopamine is a neurotransmitter used to communicate in many different areas of the brain. It is synthesized by enzymatic modification of the amino acid tyrosine. Tyrosine is found in several dietary protein sources, including eggs, cheese and fish. Once dopamine has been released by a neuron into a synapse (the space used by neurons for intercellular communication), it remains there for a short time before it is removed by re-uptake and/or degraded by enzymes.

Re-uptake

Once dopamine reaches a synapse, a specialized protein called dopamine transporter, or DAT, picks it up. The dopamine-protein complex then travels a short distance back into the cytoplasm of the cell that released it. The dopamine may then be stripped from the DAT protein and re-packaged into small vesicles for later use.

Degradation

Dopamine that is not recycled can be broken down both in the synapse and after re-uptake into the cell. The enzymes responsible for degrading dopamine are monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). The product of dopamine degradation by either MAO or COMT is homovanillic acid (HVA).

Monoamine Oxidase

Inside of the cell, MAO is found in the outer membrane of the mitochondria--the energy producing organs of the cell. Two different forms of MAO, known as MAOA and MAOB, are known to exist. The genes for both are located on the X chromosome. The two forms differ slightly in their localization and their ability to metabolize dopamine and related neurotransmitters. Because MAO is responsible for degrading dopamine, MAO deficiency results in an increase in dopamine activity. There is a class of anti-depressants known as MAOIs (monoamine oxidase inhibitors) that work by reducing the activity of MAO. Interestingly, defects in the genes encoding the two forms of MAO have been associated with mental retardation and impulsive aggressive behavior.

Catecholamine-O-methyltransferase

Catecholamine-O-methyltransferase (COMT) plays a relatively small role in dopamine metabolism and seems to be most important in degrading dopamine in the prefrontal cortex area of the brain. COMT exists as both a soluble protein and a membrane bound protein. Defects in the gene encoding the COMT protein have been associated with psychiatric disorders, including schizophrenia and bipolar disorder.

Psychostimulants and DAT

Cocaine is a psychostimulant that increases dopamine activity by blocking its re-uptake by DAT. It also blocks the re-uptake of two other neurotransmitters, norepinephrine and serotonin. A similar class of drugs, the amphetamines, increases the amount of dopamine in the synapse by stimulating DAT to "reverse-transport" dopamine.

References

• "Molecular Neuropharmacology" ; Nestler, Hyman and Malenka; 2009
• "Science"; Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A; Brunner et al; October 1993
• "Molecular Psychiatry"; The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons; Craddock, Owen and O'Donovan; February 2006

Resources

• Read this Article in Spanish
• KCI The Anti-Meth Site: Dopamine, Methamphetamines, and You