Tryptophol is an

aromatic alcohol In organic chemistry, the aromatic alcohols or aryl-alcohols are a class of chemical compounds containing a hydroxyl group (− O H) bonded indirectly to an aromatic hydrocarbon group, in contrast to the phenols, where the hydroxyl group is bonded ...

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 in 1912. It is also produced by the trypanosomal parasite in

sleeping sickness African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species '' Trypanosoma b ...

. 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 Enzyme inhibition, inhibiting the enzyme aldehyde dehydrogenase (specifically ALD ...

treatment.

Natural occurrences

Tryptophol can be found in ''

Pinus sylvestris ''Pinus sylvestris'', the Scots pine (UK), Scotch pine (US), Baltic pine, or European red pine is a species of tree in the pine family Pinaceae that is native plant, native to Eurasia. It can readily be identified by its combination of fairly s ...

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

Trypanosoma brucei ''Trypanosoma brucei'' is a species of parasitic Kinetoplastida, 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 excl ...

'') in sleeping sickness (

African trypanosomiasis African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species ''Trypanosoma bru ...

). 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 fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

''. 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 species through the production of chemicals released into the environment. Like allelopathy, it is a type of i ...

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 Felix Ehrlich 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 aromat ...

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 N ...

. 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 family Ceratobasidiaceae. Species form thin, effused, corticioid basidiocarps (fruit bodies), but are most frequently found in their sterile, anamorph state. ''Rhizoctonia'' species are saprotrophic, ...

''.

Biodegradation

In ''

Cucumis sativus The cucumber (''Cucumis sativus'') is a widely-cultivated creeping vine plant in the family Cucurbitaceae that bears cylindrical to spherical fruits, which are used as culinary vegetables.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 euglenid, a microscopic type of algae, 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 surf ...

'' 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 Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of ethanol fermentation. It was first described by Felix Ehrlich in 1912. It is also produced by the trypanosomal parasite in sleeping si ...

Biological effects

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

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

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 (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

, compounds involved in sleep regulation. Tryptophol shows

genotoxicity Genotoxicity is the chemical property, 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, bu ...

''in vitro''. Tryptophol is a

quorum sensing In biology, quorum sensing or quorum signaling (QS) is the process of cell-to-cell communication that allows bacteria to detect and respond to cell population density by gene regulation, typically as a means of acclimating to environmental disadv ...

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 (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

ingestion or

treatment, it is also associated with the study of

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

Pyrazole Pyrazole is an organic compound with the chemical formula, formula . It is a heterocycle characterized as an azole with a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in Arene substitution pattern, ortho-substi ...

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 send ...

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 Hydroxyethyl compounds