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 ]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 ...
(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 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. 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 ''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 ...
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 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 ...
, 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 ...
or 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 ''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 found in the bloodstream of patients with chronic trypanosomiasis. For that reason, it may be 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 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 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, 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 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 ...
have been shown to inhibit the conversion of exogenous tryptophol to 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 ...
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.
See also
*Wine chemistry
Wine is a complex mixture of chemical compounds in a hydro-alcoholic solution with a pH around 4.
The chemistry of wine and its resultant quality depend on achieving a balance between three aspects of the berries used to make the wine: their sugar ...
*Indole-3-carbinol
Indole-3-carbinol ( C9 H9 N O), sometimes referred to as I3C, is produced by the breakdown of the glucosinolate glucobrassicin, which can be found at relatively high levels in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussel ...
* Indole-3-butyric acid
References
{{Alcohols
Auxins
Human drug metabolites
Hypnotics
Indoles
Primary alcohols