Diamine oxidase
Diamine oxidase dimer, Human
Identifiers
EC no.1.4.3.22
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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Diamine oxidase (DAO), also known "amine oxidase, copper-containing, 1" (AOC1), formerly called histaminase,[1] is an enzyme (EC 1.4.3.22) involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermidine. The enzyme belongs to the amine oxidase (copper-containing) (AOC) family of amine oxidase enzymes.

The enzyme is expressed in bilateria, a biological group of animals. The enzyme is encoded by the AOC1 gene. This gene is highly conserved across the bilateria group which includes mammals, birds, reptiles, fish and insects, to name a few.

Chemical activity

DAO catalyzes the oxidative deamination of polyamines, such as histamine and putrescine, to produce aminoaldehydes, hydrogen peroxide, and ammonia.

DAO metabolizes histamine into imidazole-4-acetaldehyde.

Biological role

DAO is involved in the physiology of digestion and other physiological processes, such as inflammation, immune response, and wound healing. Dysfunction of DAO has been associated with various diseases, including allergies, autoimmune disorders, and cancer. DAO also plays a role in healthy pregnancy in placental mammals.

In case of a shortage or low enzymatic activity of diamine oxidase in the human body, it may appear as an allergy or histamine intolerance.[2][3][4]

Expression

In placental mammals, including humans, the highest levels of DAO expression are observed in the digestive tract (intestinal mucosa) and the placenta. DAO expression is also observed in kidney of various species.

DAO is also expressed in eosinophils.[5][6]

The role in human pregnancy

In humans, a certain subtype of cells of the placenta, namely the extravillous trophoblasts, express the enzyme and secrete it into the blood stream of a pregnant woman.[7]

During pregnancy, DAO plays a crucial role in maintaining fetal growth and development by regulating histamine levels.[7] DAO levels in the blood circulation increases vastly in pregnant women suggesting a protective mechanism against adverse histamine.[8] Histamine is a potent vasodilator and can cause uterine contractions, which can lead to premature labor. DAO in the placenta breaks down histamine to prevent its accumulation and maintain a healthy pregnancy. Low levels of DAO in the placenta may contribute to preeclampsia, a pregnancy-related disorder characterized by mother's high blood pressure and damage to mother's organs such as the liver and kidneys; the baby may also be affected if the condition is severe or left untreated, but it is not the primary target of the disorder.

Lowered diamine oxidase values in maternal blood in early pregnancy might be an indication for trophoblast-related pregnancy disorders like early-onset preeclampsia.[8]

Research

Exogenous DAO (supplements) are being studied as complementary treatment[9] for the relief of histamine intolerance symptoms, and other conditions, such as migraine[10] or fibromyalgia.[11] However, the results are inconclusive because studies to date have involved small study populations and short intervention periods.[12][13][14]

Although DAO supplements may have some benefits, research is limited. DAO supplements are available over the counter but are not FDA-approved.[15]

References

  1. ↑ Wolvekamp MC, de Bruin RW (1994). "Diamine oxidase: an overview of historical, biochemical and functional aspects". Digestive Diseases. 12 (1): 2–14. doi:10.1159/000171432. PMID 8200121.
  2. ↑ Arih K, Đorđević N, Košnik M, Rijavec M (October 2023). "Evaluation of Serum Diamine Oxidase as a Diagnostic Test for Histamine Intolerance". Nutrients. 15 (19): 4246. doi:10.3390/nu15194246. PMC 10574399. PMID 37836530.
  3. ↑ Manzotti G, Breda D, Di Gioacchino M, Burastero SE (March 2016). "Serum diamine oxidase activity in patients with histamine intolerance". International Journal of Immunopathology and Pharmacology. 29 (1): 105–11. doi:10.1177/0394632015617170. PMC 5806734. PMID 26574488.
  4. ↑ Music E, Silar M, Korosec P, Kosnik M, Rijavec M (2011). "Serum diamine oxidase (DAO) activity as a diagnostic test for histamine intolerance". Clinical and Translational Allergy. 1 (Suppl 1): P115. doi:10.1186/2045-7022-1-S1-P115. PMC 3354134.
  5. ↑ Zeiger RS, Colten HR (February 1977). "Histaminase release from human eosinophils". Journal of Immunology. 118 (2): 540–3. doi:10.4049/jimmunol.118.2.540. PMID 402420. S2CID 36128339.
  6. ↑ Agúndez JA, Ayuso P, Cornejo-García JA, Blanca M, Torres MJ, Doña I, et al. (2012). "The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs". PLOS ONE. 7 (11): e47571. Bibcode:2012PLoSO...747571A. doi:10.1371/journal.pone.0047571. PMC 3495953. PMID 23152756.
  7. 1 2 Maintz L, Schwarzer V, Bieber T, van der Ven K, Novak N (2008). "Effects of histamine and diamine oxidase activities on pregnancy: a critical review". Hum Reprod Update. 14 (5): 485–95. doi:10.1093/humupd/dmn014. PMID 18499706.
  8. 1 2 Velicky P, Windsperger K, Petroczi K, Pils S, Reiter B, Weiss T, et al. (April 2018). "Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia". Scientific Reports. 8 (1): 6342. Bibcode:2018NatSR...8.6342V. doi:10.1038/s41598-018-24652-0. PMC 5910386. PMID 29679053.
  9. ↑ Hakl R, Litzman J (2023). "Histamine intolerance". Vnitr Lek. 69 (1): 37–40. doi:10.36290/vnl.2023.005. PMID 36931880. S2CID 257604532.
  10. ↑ Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, Vidal-Carou MC (February 2019). "Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial". Clin Nutr. 38 (1): 152–158. doi:10.1016/j.clnu.2018.01.013. hdl:2445/162978. PMID 29475774. S2CID 3511305.
  11. ↑ Okutan G, Sánchez Niño GM, Terrén Lora A, López Oliva S, San Mauro Martín I (October 2023). "Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial". J Clin Med. 12 (20): 6449. doi:10.3390/jcm12206449. PMC 10607251. PMID 37892588.
  12. ↑ Schnedl WJ, Enko D (April 2021). "Histamine Intolerance Originates in the Gut". Nutrients. 13 (4): 1262. doi:10.3390/nu13041262. PMC 8069563. PMID 33921522.
  13. ↑ Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MC (August 2020). "Histamine Intolerance: The Current State of the Art". Biomolecules. 10 (8): 1181. doi:10.3390/biom10081181. PMC 7463562. PMID 32824107.
  14. ↑ Hrubisko M, Danis R, Huorka M, Wawruch M (June 2021). "Histamine Intolerance-The More We Know the Less We Know. A Review". Nutrients. 13 (7): 2228. doi:10.3390/nu13072228. PMC 8308327. PMID 34209583.
  15. ↑ "regulations.gov search for diamine oxidase".
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