Dopamine, a Circadian Rhythm Neurotransmitter, What Is It and Why Is It Important?
Most people associate happiness with serotonin and the use of antidepressants, but serotonin is more of a neurotransmitter related to mood stabilization and wakefulness. Though both neurotransmitters are associated with alertness, dopamine is one of the main hormones which makes us feel happy and motivated. However, when dopamine homeostasis is disrupted, anxiety, mania, apathy, and depression occur depending on the fluctuation of the neurotransmitter. We are exposed to many dopamine manipulators within our modern life, from our Facebook addiction, excessive blue light exposure, gambling, to an epidemic of narcotics abuse. What is dopamine? What does proper dopamine regulation do with our circadian rhythm, and how can it be returned to homeostasis when needed?
What is Dopamine?
Dopamine is an organic catechol of the catecholamine and phenethylamine families that is needed by our body for many different crucial functions. Dopamine is an amine made by removing a carboxyl group from its precursor L-DOPA (which many people know is a popular medication for Parkison’s disease). L-DOPA is produced from the amino acid L-tyrosine from catalyzation by the rate-limiting enzyme tyrosine hydroxylase, using oxygen, iron, and tetrahydrobiopterin (BH4) as cofactors. L-DOPA is synthesized within the brain, nervous system, pancreas, and kidneys. L-phenylalanine must be metabolized into L-tyrosine using tyrosine hydroxylase to become L-DOPA. For the proper production of L-DOPA, pyridoxal phosphate (vitamin B6) is required. Finally, producing catecholamines from L-tyrosine, including dopamine, eventually traps the active-site iron in the Fe(III) state within the cell’s cytosol, inhibiting tyrosine hydroxylase. Inhibition of tyrosine hydroxylase temporarily reduces catecholamine production, maintaining proper homeostasis. Eventually, the body needs more catecholamines, and the active sites open back up from a reduction in circulating catecholamine leading to the production of tyrosine hydroxylase, increasing catecholamine production.[1] [2] [3]
Plants produce dopamine, and many foods that we consume contain it. Ingesting dopamine from food does not increase the dopamine within our brain; ingested dopamine is metabolized into dopamine sulfate within the mesentery, enters the bloodstream, is filtered by the kidneys, and is excreted. “Plasma dopamine sulfate derives mainly from sulfoconjugation of dopamine synthesized from L-DOPA in the gastrointestinal tract. Both dietary and endogenous determinants affect plasma dopamine sulfate. The findings suggest an enzymatic gut-blood barrier for detoxifying exogenous dopamine and delimiting autocrine/paracrine effects of endogenous dopamine generated in a third catecholamine system.”[4] [5]
Dopamine cannot cross the blood-brain barrier because it lacks a proper transporter and is not lipid-soluble (L-DOPA, however, can). What is needed by the brain must be produced within. Dopamine is also a precursor for synthesizing the neurotransmitters norepinephrine and epinephrine. Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase, which requires copper, oxygen, and ascorbic acid to be produced. Norepinephrine is converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl-L-methionine as the cofactor. Dopamine is broken down into homovanillic acid and catabolized by three enzymes, monoamine oxidase, catechol-O-methyltransferase, and aldehyde dehydrogenase, to be eliminated by the kidneys in urine. Any polymorphisms in the genes that code these enzymes (which cause a deficiency in those enzymes) can lead to improper dopamine homeostasis.[6] [7] [8]
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