5-Hydroxyindoleacetaldehyde
Inactive metabolite of the neurotransmitter serotonin
5-Hydroxyindoleacetaldehyde
Names
IUPAC name
2-(5-hydroxy-1H -indol-3-yl)acetaldehyde
Other names
5-Hydroxyindole-acetaldehyde; 5-HIAL; 5-HIAAL; 5-Hydroxytryptaldehyde; 5-Hydroxyindole-3-acetaldehyde; Serotonin aldehyde
[ 1]
Identifiers
ChEBI
ChemSpider
KEGG
UNII
InChI=1S/C10H9NO2/c12-4-3-7-6-11-10-2-1-8(13)5-9(7)10/h1-2,4-6,11,13H,3H2
Key: OBFAPCIUSYHFIE-UHFFFAOYSA-N
C1=CC2=C(C=C1O)C(=CN2)CC=O
Properties
C 10 H 9 N O 2
Molar mass
175.18 g/mol
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
5-Hydroxyindoleacetaldehyde (5-HIAL ), also known as 5-hydroxytryptaldehyde or as serotonin aldehyde , is an inactive metabolite and metabolic intermediate of the monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT).[ 2] [ 3] [ 1]
5-HIAL is formed from serotonin by oxidative deamination via monoamine oxidase (MAO).[ 2] [ 3] MAO-mediated deamination is the primary metabolic pathway of serotonin inactivation.[ 2] Monoamine oxidase A (MAO-A) has about 120-fold higher affinity for serotonin than monoamine oxidase B (MAO-B).[ 2] In relation to this, MAO-A is the main isozyme of MAO involved in serotonin degradation.[ 2]
Following its formation, 5-HIAL is metabolized by aldehyde dehydrogenase (ALDH) to form 5-hydroxyindoleacetic acid (5-HIAA).[ 2] [ 3] 5-HIAL can also be converted into small amounts of 5-hydroxytryptophol (5-HTOL; also known as 5-hydroxyindolethanol or 5-HIET) by either aldehyde reductase (ALR/ALDR) or alcohol dehydrogenase (ADH).[ 2] [ 4] However, brain concentrations of 5-HTOL are only 1 to 5% of those of 5-HIAA.[ 2] [ 4]
Use of ethanol (alcohol) can dramatically increase 5-HTOL formation by inhibiting ALDH and enhancing ADH activity.[ 2] [ 5] As a result, the ratio of 5-HTOL to 5-HIAA is a sensitive and reliable marker of recent ethanol ingestion and has been suggested for use in clinical and forensic contexts.[ 2] [ 5]
Besides oxidative deamination by MAO into 5-HIAL, serotonin can also be conjugated by glucuronidation via glucuronyltransferases , conjugated by sulfation via sulfotransferases , acetylated and then methylated into melatonin (N -acetyl-5-methoxytryptamine) (which occurs mainly in the pineal gland ), and converted into certain other metabolites like 5-hydroxyindole thiazoladine carboxylic acid (5-HITCA).[ 2] However, these secondary metabolic pathways appear to play only a minor role in serotonin metabolism.[ 2]
5-HIAL has been implicated in producing neurotoxicity and in the development and progression of neurodegenerative diseases .[ 6] [ 7] [ 8]
See also
References
^ a b Jinsmaa Y, Cooney A, Sullivan P, Sharabi Y, Goldstein DS (March 2015). "The serotonin aldehyde, 5-HIAL, oligomerizes alpha-synuclein" . Neurosci Lett . 590 : 134–137. doi :10.1016/j.neulet.2015.01.064 . PMC 4755587 . PMID 25637699 .
^ a b c d e f g h i j k l Bortolato, Marco; Chen, Kevin; Shih, Jean C. (2010). "The Degradation of Serotonin: Role of MAO". Handbook of Behavioral Neuroscience . Vol. 21. Elsevier. pp. 203–218. doi :10.1016/s1569-7339(10)70079-5 . ISBN 978-0-12-374634-4 .
^ a b c Matthes S, Mosienko V, Bashammakh S, Alenina N, Bader M (2010). "Tryptophan hydroxylase as novel target for the treatment of depressive disorders". Pharmacology . 85 (2): 95–109. doi :10.1159/000279322 . PMID 20130443 .
^ a b Bortolato M, Shih JC (2011). "Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence" . Int Rev Neurobiol . International Review of Neurobiology. 100 : 13–42. doi :10.1016/B978-0-12-386467-3.00002-9 . ISBN 978-0-12-386467-3 . PMC 3371272 . PMID 21971001 .
^ a b Beck O, Helander A (December 2003). "5-hydroxytryptophol as a marker for recent alcohol intake". Addiction . 98 Suppl 2: 63–72. doi :10.1046/j.1359-6357.2003.00583.x . PMID 14984243 .
^ Cagle BS, Crawford RA, Doorn JA (February 2019). "Biogenic Aldehyde-Mediated Mechanisms of Toxicity in Neurodegenerative Disease" . Curr Opin Toxicol . 13 : 16–21. Bibcode :2019COTox..13...16C . doi :10.1016/j.cotox.2018.12.002 . PMC 6625780 . PMID 31304429 .
^ Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, Todd KG, Wood PL, Baker GB (January 2022). "Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine" . Cell Mol Neurobiol . 42 (1): 225–242. doi :10.1007/s10571-021-01078-3 . PMC 8732914 . PMID 33839994 .
^ Behl T, Kaur D, Sehgal A, Singh S, Sharma N, Zengin G, Andronie-Cioara FL, Toma MM, Bungau S, Bumbu AG (June 2021). "Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors" . Molecules . 26 (12): 3724. doi :10.3390/molecules26123724 . PMC 8234097 . PMID 34207264 .
Dopaminergic Noradrenergic Serotonergic
2'-Amino-MPTP
2,4-DCA
2,4,5-THA
2,4,5-THMA
3-CA
3,4-DCA
4-CAB (α-ethyl-PCA)
5-IAI
5,6-DHT
5,7-DHT
α-Me-DA (3,4-DHA)
α,N -Dimethyldopamine
αET
DCA
Fenfluramine
Haloperidol
HPP+
HPTP
MBDB
MDA (tenamfetamine)
MDAI
MDEA
MDMA (midomafetamine)
Methamphetamine
MMAI
Norfenfluramine
PBA
PCA
PCMA
PIA
Unsorted