Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of

ethanol fermentation Ethanol fermentation, also called alcoholic fermentation, is a biological process which converts sugars such as glucose, fructose, and sucrose into cellular energy, producing ethanol and carbon dioxide as by-products. Because yeasts perform this ...

. It was first described by

Felix Ehrlich Felix Ehrlich (16 June 1877 in Harriehausen (today incorporated into Bad Gandersheim) – 23 January 1942 in Obernigk near Breslau) was a German chemist and biochemist. Life and work Felix Ehrlich studied in Berlin and Munich. After receiving h ...

in 1912. It is also produced by the trypanosomal parasite in sleeping sickness. It forms in the liver as a side-effect of

disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects o ...

treatment.

Natural occurrences

Tryptophol can be found in ''

Pinus sylvestris ''Pinus sylvestris'', the Scots pine (UK), Scotch pine (US) or Baltic pine, is a species of tree in the pine family Pinaceae that is native to Eurasia. It can readily be identified by its combination of fairly short, blue-green leaves and or ...

'' needles or seeds. It is produced by the trypanosomal parasite (''

Trypanosoma brucei ''Trypanosoma brucei'' is a species of parasitic kinetoplastid belonging to the genus '' Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extrace ...

'') in sleeping sickness (

African trypanosomiasis African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species '' Trypanosoma brucei''. Humans are infected by two t ...

). Tryptophol is found in wine and beer as a secondary product of

(a product also known as congener) by ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...

''. It is also an

autoantibiotic Autotoxicity, meaning self-toxicity, is a biological phenomenon whereby a species inhibits growth or reproduction of other members of its same species through the production of chemicals released into the environment. Like allelopathy, it is a type ...

produced by the fungus ''

Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...

. It can also be isolated from the marine sponge '' Ircinia spiculosa''.

Metabolism

Biosynthesis

It was first described by

in 1912. Ehrlich demonstrated that yeast attacks the natural amino acids essentially by splitting off carbon dioxide and replacing the amino group with hydroxyl. By this reaction,

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. 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 ...

gives rise to tryptophol. Tryptophan is first deaminated to 3-indolepyruvate. It is then decarboxylated to indole acetaldehyde by indolepyruvate decarboxylase. This latter compound is transformed to tryptophol by

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NA ...

. It is formed from tryptophan, along with

indole-3-acetic acid Indole-3-acetic acid (IAA, 3-IAA) is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, con ...

in rats infected by ''

gambiense''. An efficient conversion of tryptophan to indole-3-acetic acid and/or tryptophol can be achieved by some species of fungi in the genus ''

Rhizoctonia ''Rhizoctonia'' is a genus of fungi in the order Cantharellales. Species form thin, effused, corticioid basidiocarps (fruit bodies), but are most frequently found in their sterile, anamorphic state. ''Rhizoctonia'' species are saprotrophic, bu ...

''.

Biodegradation

In '' Cucumis sativus'' (cucumber), the enzymes indole-3-acetaldehyde reductase (NADH) and indole-3-acetaldehyde reductase (NADPH) use tryptophol to form (indol-3-yl)acetaldehyde.

Glycosides

The unicellular alga ''

Euglena gracilis ''Euglena gracilis'' is a freshwater species of single-celled alga in the genus '' Euglena''. It has secondary chloroplasts, and is a mixotroph able to feed by photosynthesis or phagocytosis. It has a highly flexible cell surface, allowing it ...

'' converts exogenous tryptophol to two major metabolites: tryptophol galactoside and an unknown compound (a tryptophol ester), and to minor amounts of

, tryptophol acetate, and tryptophol glucoside.

Biological effects

Tryptophol and its derivatives 5-hydroxytryptophol and 5-methoxytryptophol, induce

sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited Perception, sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefuln ...

in mice. It induces a sleep-like state that lasts less than an hour at the 250 mg/kg dose. These compounds may play a role in physiological sleep mechanisms. It may be a functional analog of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrat ...

, compounds involved in sleep regulation. Tryptophol shows

genotoxicity Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic ...

''in vitro''. Tryptophol is a

quorum sensing In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...

molecule for the yeast ''

''. It is also found in the bloodstream of patients with chronic trypanosomiasis. For that reason, it may be a

molecule for the trypanosome parasite. In the case of trypanosome infection, tryptophol decreases the immune response of the host. As it is formed in the liver after

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

ingestion or

treatment, it is also associated with the study of

alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...

Pyrazole Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with p''K''b 11.5 ( ...

and

have been shown to inhibit the conversion of exogenous tryptophol to

and to potentiate the sleep-inducing hypothermic effects of tryptophol in mice. It is a growth promoter of cucumber

hypocotyl The hypocotyl (short for "hypocotyledonous stem", meaning "below seed leaf") is the stem of a germinating seedling, found below the cotyledons (seed leaves) and above the radicle ( root). Eudicots As the plant embryo grows at germination, it ...

segments. The auxinic action in terms of embryo formation is even better for tryptophol arabinoside on ''

Cucurbita pepo ''Cucurbita pepo'' is a cultivated plant of the genus ''Cucurbita''. It yields varieties of winter squash and pumpkin, but the most widespread varieties belong to the subspecies ''Cucurbita pepo'' subsp. ''pepo'', called summer squash. It has b ...

'' hypocotyl fragments.

References

{{Alcohols Auxins Human drug metabolites Hypnotics Indoles Primary alcohols