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Eosinophilia–myalgia syndrome is a rare, sometimes fatal neurological condition linked to the ingestion of the dietary supplement L-tryptophan. [1] [2] The risk of developing EMS increases with larger doses of tryptophan and increasing age. [3]
Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B 3 (niacin). [4] It is encoded by the codon UGG.
Droxidopa (L-DOPS) is a synthetic precursor or prodrug of norepinephrine used orally in the treatment of certain types of hypotension and other conditions. [ 6 ] [ 7 ] Dipivefrine is a synthetic precursor or prodrug of epinephrine used as an ophthalmic medication .
l-Kynurenine is a metabolite of the amino acid l-tryptophan used in the production of niacin. Kynurenine is synthesized by the enzyme tryptophan dioxygenase , which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygenase , which is made in many tissues in response to immune activation. [ 1 ]
But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the toxic oil syndrome in Spain in 1981.
l-DOPA, also known as l-3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants [2] and animals, including humans. Humans, as well as a portion of the other animals that utilize l -DOPA, make it via biosynthesis from the amino acid l -tyrosine .
Some β-carbolines, notably tetrahydro-β-carbolines, may be formed naturally in plants and the human body with tryptophan, serotonin and tryptamine as precursors. Altogether, eight plant families are known to express 64 different kinds of β-carboline alkaloids.
Metabolites involved in the kynurenine pathway include tryptophan, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, and 3-hydroxykynurenine. [2] [3] The kynurenine pathway is responsible for about 95% of total tryptophan catabolism. [4] Disruption in the pathway is associated with certain genetic and psychiatric disorders. [5] [2 ...