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 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 of ...

treatment.

Natural occurrences

Tryptophol can be found in '' Pinus sylvestris'' 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 exclus ...

'') 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 typ ...

). Tryptophol is found in wine and beer as a secondary product of ethanol fermentation (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 been o ...

''. 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. 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 Indole-3-acetaldehyde belongs to the class of organic compounds known as indoles. These are compounds containing an indole moiety, which consists of pyrrole ring fused to benzene to form 2,3-benzopyrrole. Indole-3-acetaldehyde is a substrate fo ...

indolepyruvate decarboxylase The enzyme indolepyruvate decarboxylase () catalyzes the chemical reaction :3-(indol-3-yl)pyruvate \rightleftharpoons 2-(indol-3-yl)acetaldehyde + CO2 This enzyme belongs to the family of lyases, specifically the carboxy-lyases, which cleave ca ...

. This latter compound is transformed to tryptophol by alcohol dehydrogenase. It is formed from tryptophan, along with indole-3-acetic acid 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''.

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 to ...

'' converts exogenous tryptophol to two major metabolites: tryptophol galactoside and an unknown compound (a tryptophol ester), and to minor amounts of indole-3-acetic acid, 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 sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...

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 vas ...

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 vertebrates ...

, 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 sub ...

''in vitro''. Tryptophol is a quorum sensing molecule for the yeast ''

''. It is also found in the bloodstream of patients with chronic trypanosomiasis. For that reason, it may be a quorum sensing 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 (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

ingestion or

treatment, it is also associated with the study of

alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...

. Pyrazole and

have been shown to inhibit the conversion of exogenous tryptophol to indole-3-acetic acid 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'' hypocotyl fragments.

References

{{Alcohols Auxins Human drug metabolites Hypnotics Indoles Primary alcohols