Melatonin, the Sleep Hormone
Melatonin is a neurotransmitter, hormone, and antioxidant originally believed only to be produced and released by our pineal gland. Recent research indicates that our mitochondria are what have melatonin within the cell. Melatonin is important for overall health as both an antioxidant, neurotransmitter, and circadian rhythm regulator (most of the pineal produces melatonin between midnight and 8:00 am). Melatonin improves sleep quality and duration. Melatonin also reduces blood pressure and leptin levels (the hormone that inhibits hunger) during sleep. Finally, differing melatonin concentrations are found in other parts of our body outside of our brain, leading researchers to believe that our mitochondria and microbiome produce it.[1] [2] [3] [4]
Tryptophan is converted into 5-hydroxytryptophan, which is further converted into serotonin. Serotonin is converted into N-acetylserotonin by the enzyme arylalkylamine N-acetyltransferase. N-acetylserotonin is then converted into melatonin by the related limited enzyme hydroxyindole-O-methyltransferase (HIOMT). Melatonin is not stored within the pineal gland but diffuses into the capillary blood and cerebrospinal fluid. Cerebrospinal fluid melatonin levels are higher in the third ventricle than the lateral one, thus indicating that melatonin enters the cerebrospinal fluid through the pineal recess, even during the daytime, albeit in lesser amounts. [5] [6]
In plasma circulation, melatonin is partially bound to albumin and binds to hemoglobin. Circulating melatonin is metabolized mainly within the liver, where it is first hydroxylated by cytochrome P450 mono-oxygenases (CYP1B1, CYP1A2, CYP1A1). After melatonin is hydroxylated, it is then conjugated with sulfate and enters the bloodstream to be excreted by the kidneys as 6-sulfatoxymelatonin. In the brain, melatonin can be metabolized into 6-sulfatoxymelatonin and kynuramine derivatives. These kynuramine metabolites of melatonin, which are formed in the brain, namely, N 1-acetyl-N 2-formyl-5-methoxy kynuramine and N 1-acetyl-5-methoxykynuramine also contain antioxidant and anti-inflammatory properties. Finally, melatonin is an antagonist to dopamine.[7] [8] [9] [10]
Recent studies have shown that melatonin is also synthesized by our gut flora and rates at least four hundred times greater than our pineal gland. Large quantities of melatonin have been found within our vermiform appendix, which appears to be a safe house for probiotic flora during gastrointestinal infection. Like other lifeforms on Earth, bacteria have a circadian rhythm, so they also produce melatonin in the dark and possibly as a signaling hormone. Finally, just like bacteria that produce melatonin, our mitochondria have recently been discovered to produce melatonin.[11] [12] [13] [14]
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