Chemistry:5-Hydroxyindoleacetaldehyde

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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).[1][2][3]

5-HIAL is formed from serotonin by oxidative deamination via monoamine oxidase (MAO).[1][2] MAO-mediated deamination is the primary metabolic pathway of serotonin inactivation.[1] Monoamine oxidase A (MAO-A) has about 120-fold higher affinity for serotonin than monoamine oxidase B (MAO-B).[1] In relation to this, MAO-A is the main isozyme of MAO involved in serotonin degradation.[1]

Following its formation, 5-HIAL is metabolized by aldehyde dehydrogenase (ALDH) to form 5-hydroxyindoleacetic acid (5-HIAA).[1][2] 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).[1][4] However, brain concentrations of 5-HTOL are only 1 to 5% of those of 5-HIAA.[1][4]

Use of ethanol (alcohol) can dramatically increase 5-HTOL formation by inhibiting ALDH and enhancing ADH activity.[1][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.[1][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).[1] However, these secondary metabolic pathways appear to play only a minor role in serotonin metabolism.[1]

5-HIAL has been implicated in producing neurotoxicity and in the development and progression of neurodegenerative diseases.[6][7][8]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Bortolato, Marco; Chen, Kevin; Shih, Jean C. (2010). "The Degradation of Serotonin: Role of MAO". Handbook of Behavioral Neuroscience. 21. Elsevier. pp. 203–218. doi:10.1016/s1569-7339(10)70079-5. ISBN 978-0-12-374634-4. 
  2. ↑ 2.0 2.1 2.2 "Tryptophan hydroxylase as novel target for the treatment of depressive disorders". Pharmacology 85 (2): 95–109. 2010. doi:10.1159/000279322. PMID 20130443. 
  3. ↑ "The serotonin aldehyde, 5-HIAL, oligomerizes alpha-synuclein". Neurosci Lett 590: 134–137. March 2015. doi:10.1016/j.neulet.2015.01.064. PMID 25637699. 
  4. ↑ 4.0 4.1 "Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence". Int Rev Neurobiol. International Review of Neurobiology 100: 13–42. 2011. doi:10.1016/B978-0-12-386467-3.00002-9. ISBN 978-0-12-386467-3. PMID 21971001. 
  5. ↑ 5.0 5.1 "5-hydroxytryptophol as a marker for recent alcohol intake". Addiction 98 Suppl 2: 63–72. December 2003. doi:10.1046/j.1359-6357.2003.00583.x. PMID 14984243. 
  6. ↑ "Biogenic Aldehyde-Mediated Mechanisms of Toxicity in Neurodegenerative Disease". Curr Opin Toxicol 13: 16–21. February 2019. doi:10.1016/j.cotox.2018.12.002. PMID 31304429. Bibcode: 2019COTox..13...16C. 
  7. ↑ "Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine". Cell Mol Neurobiol 42 (1): 225–242. January 2022. doi:10.1007/s10571-021-01078-3. PMID 33839994. 
  8. ↑ "Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors". Molecules 26 (12): 3724. June 2021. doi:10.3390/molecules26123724. PMID 34207264. 

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