5-Hydroxyindoleacetaldehyde
5-Hydroxyindoleacetaldehyde, also known as 5-hydroxytryptaldehyde or as serotonin aldehyde, is an inactive metabolite and metabolic intermediate of the monoamine neurotransmitter serotonin.
5-HIAL is formed from serotonin by oxidative deamination via monoamine oxidase. MAO-mediated deamination is the primary metabolic pathway of serotonin inactivation. Monoamine oxidase A has about 120-fold higher affinity for serotonin than monoamine oxidase B. In relation to this, MAO-A is the main isozyme of MAO involved in serotonin degradation.
Following its formation, 5-HIAL is metabolized by aldehyde dehydrogenase to form 5-hydroxyindoleacetic acid. 5-HIAL can also be converted into small amounts of 5-hydroxytryptophol by either aldehyde reductase or alcohol dehydrogenase. However, brain concentrations of 5-HTOL are only 1 to 5% of those of 5-HIAA.
Use of ethanol can dramatically increase 5-HTOL formation by inhibiting ALDH and enhancing ADH activity. 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.
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 , and converted into certain other metabolites like 5-hydroxyindole thiazoladine carboxylic acid. However, these secondary metabolic pathways appear to play only a minor role in serotonin metabolism.
5-HIAL has been implicated in producing neurotoxicity and in the development and progression of neurodegenerative diseases.