Inactive metabolite of the neurotransmitter serotonin
5-Hydroxyindoleacetaldehyde Names IUPAC name 2-(5-hydroxy-1H -indol-3-yl)acetaldehyde
Other names5-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
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 as5-hydroxytryptaldehyde or asserotonin aldehyde , is aninactive metabolite andmetabolic intermediate of themonoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT).[ 2] [ 3] [ 1]
5-HIAL is formed from serotonin byoxidative deamination viamonoamine oxidase (MAO).[ 2] [ 3] metabolic pathway of serotonin inactivation.[ 2] Monoamine oxidase A (MAO-A) has about 120-fold higheraffinity for serotonin thanmonoamine oxidase B (MAO-B).[ 2] isozyme of MAO involved in serotonin degradation.[ 2]
Following its formation, 5-HIAL is metabolized byaldehyde dehydrogenase (ALDH) to form5-hydroxyindoleacetic acid (5-HIAA).[ 2] [ 3] 5-hydroxytryptophol (5-HTOL; also known as 5-hydroxyindolethanol or 5-HIET) by eitheraldehyde reductase (ALR/ALDR) oralcohol dehydrogenase (ADH).[ 2] [ 4] [ 2] [ 4]
Use ofethanol (alcohol) can dramatically increase 5-HTOL formation by inhibiting ALDH and enhancing ADH activity.[ 2] [ 5] 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 beconjugated byglucuronidation viaglucuronyltransferases , conjugated bysulfation viasulfotransferases ,acetylated and thenmethylated intomelatonin (N -acetyl-5-methoxytryptamine) (which occurs mainly in thepineal gland ), and converted into certain other metabolites like5-hydroxyindole thiazoladine carboxylic acid (5-HITCA).[ 2] [ 2]
5-HIAL has been implicated in producingneurotoxicity and in the development and progression ofneurodegenerative diseases .[ 6] [ 7] [ 8]
^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′-NH2 -MPTP (2′-amino-MPTP) 2,4-DCA 2,4,5-THA 2,4,5-THMA 3-CA 3,4-DCA 4-CAB (α-ethyl-PCA) 4-CMA 4-HO-5-MeO-T 4,5-DHT 5-IAI 5-MAPB 5-MeO-DiPT 5,6-DHT 5,7-DHT 6,7-DHT αET ETAI Fenfluramine Haloperidol HHA (α-methyldopamine) HHMA (α-methylepinine, α,N -dimethyldopamine) HPP+ HPTP MBDB MDA (tenamfetamine) MDMA (midomafetamine) Mephedrone Methamphetamine Methylone Norfenfluramine PBA PBMA PCA PCMA PIA TAI Unsorted
