Monoamine oxidases

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Monoamine oxidases
Identifier
Gene name (s) MAOA , MAOB
Enzyme classification
EC, category 1.4.3.4 ,  oxidoreductase
Response type Redox reaction
Substrate Monoamine + H 2 O + O 2
Products Aldehyde + NH 3 + H 2 O 2
Occurrence
Parent taxon Eukaryotes

The monoamine oxidases ( MAO ) are mitochondrial enzymes that break down monoamines by deamination with the help of H 2 O and O 2 to the corresponding aldehydes , ammonia and hydrogen peroxide . These reactions are part of the biotransformation in eukaryotes and serve to break down toxic substances.

A distinction is made between monoamine oxidase-A ( MAO-A ), the distant homolog of which has also been detected in fungi, and paralogous monoamine oxidase-B ( MAO-B ), which is only found in mammals . MAOs are membrane proteins found in the outer mitochondrial membrane . Both MAO genes are located on the short arm of the X chromosome .

MAO-A and MAO-B are found in the brain in the astrocytes and neurons , but also outside the brain. Both MAO enzymes are mainly located in the outer membrane of the mitochondria.

Deamination by MAO-A and MAO-B

Deamination by MAO-A and MAO-B has both similarities and specializations. In detail:

The deamination of serotonin, adrenaline, noradrenaline and dopamine takes place with the formation of the following breakdown products:

Some degradation products of the catechol-O-methyltransferase are further broken down by the MAO-A:

MAO-A

In humans, MAO-A is found outside the brain, mainly in the nerve endings of the sympathetic nervous system , in the mucous membranes of the intestines and in the placenta . It breaks down the monoamine neurotransmitters serotonin, norepinephrine and dopamine, in descending order according to the influence of MAO-A on their breakdown. Mutations in the MAOA gene or in its promoter can lead to MAO-A deficiency and, if it fails completely, to Brunner syndrome, which is associated with mild intellectual disabilities. The direct association of MAO-A deficiency with addictive and aggressive behavior has not yet been proven in any study.

MAO-A variants and human behavior

The localization of the MAO genes in humans on the X chromosome makes it difficult, on the one hand, to make statements that are equally valid for men and women, and, on the other, to transfer results from animal experiments to humans. The reason is that men only wear one copy of the X and changes to the MAO-A gene have so different effects than if a normal copy were still present. Nevertheless, gene variants were found that were also associated with behavioral changes in studies with a large number of participants, albeit only under certain conditions. For example, it has been shown that an allele of the MAO-A gene that has a lower transcription efficiency is associated with higher debt.

The Brunner syndrome

A complete failure of monoamine oxidase A (monoamine oxidase A deficiency) can lead to Brunner syndrome .

The Dunedin MAO Study

The Dunedin Multidisciplinary Health and Development Study is a long-term cohort study that follows 1047 people born in Dunedin , New Zealand over a given year . In 2002, Caspi and co-authors examined the hypothesis of whether men who were abused as children deal differently with their pasts, and whether any differences in it depend on the level of MAO-A activity. It was known from previous studies that abused animal pups have similar changes in urine monoamine levels as under MAO-A deficiency.

Using a so-called VNTR in the promoter of the MAOA gene, Caspi, among others, estimated the MAO-A activity and classified it in two baskets: high and low. Furthermore, so-called antisocial behavior was determined by the occurrence of one of four symptoms, with each symptom being assessed independently according to a corresponding norm. In all four groups who experienced an antisocial symptom, low MAO-A levels were a clear risk factor for it. Taken as a whole, those abused with a low MAO-A score made up 12 percent of the total, but 44 percent of those convicted of violence. 85 percent of abused men with low MAO-A scores developed the antisocial behavior defined by the study.

Between 2004 and 2006, six further studies were published, some of which confirmed the results of the Dunedin Caspis study, but in some cases could not find any evidence of them. The work of Frazzetto and co-authors is noteworthy because of the number of participants Childhood are associated with an increased risk of later aggressive behavior.

Warrior Gene and the Māori

At the 73rd Conference of the American Association of Physical Anthropologists in 2004, Gibbons presented data on the MAOA gene in other primates and speculated on the possibility that certain variants of the gene might have given carriers an evolutionary advantage. He called these variants or the gene the warrior gene (German: warrior gene ). However, so far the only conclusive results of studies with a large number of participants have only been obtained with severe MAO deficiency or with child abuse.

The term warrior gene first became popular in the mass media after Lea and co-authors published data at the thirteenth international Congress of Human Genetics in 2006 that were supposed to show that the South Pacific spread of the Māori was associated with a higher probability of low MAO-A values . Here, too, a direct connection with the behavior was suggested, which is not certain. In addition, the work by Caspi, to which Lea was referring, was carried out with participants of European descent, while Lea's data came from 17 Māori, of which 60 percent had lowered MAO-A values.

New Zealand and national media then circulated Lea's claims along with interview quotes. After publishing criticism from the scientific ranks, Lea responded with a specialist article in which he accused the Australian Press Association of misunderstandings and incorrect quotations. The establishment of an ethics committee with Māori participation was announced. Their comprehensive review was published in 2009 under the title “Warrior Genes and the Disease of Māori Being” and, in addition to the obvious scientific problems of the previous work, emphasizes that none of the mental illnesses associated with MAO-A deficiency in the literature for such a company as the colonization of the South Pacific or the military fitness of warriors are beneficial.

MAO-B

Effect of a TAAR1- ( English trace amine-associated receptor 1 ) agonists to a Neuron

The MAO-B breaks down in particular β- phenylethylamine (PEA) and benzylamine in the CNS , and like the MAO-A dopamine. Its role in breaking down the neurotransmitter dopamine makes drug-blocking MAO-B one of the possible options in the treatment of Parkinson's disease . The breakdown of PEA leads indirectly (presumably through lower TAAR1 activation) to a lower release of the neurotransmitter norepinephrine, which is broken down by the MAO-A. A drug-based (partial) blockade of both MAO enzymes therefore has a stronger effect on the norepinephrine level than the selective blockade of MAO-A.

Marvin Zuckerman examined biochemical correlates related to sensation seeking . Accordingly, MAO-B concentrations correlate negatively with self-assessed sensation seeking (but also aggressiveness and impulsiveness).

MAOIs

There are natural and artificially synthesized substances that inhibit this enzyme and are accordingly called monoamine oxidase inhibitors (MAOH). Some drugs with MAOH effects are used as antidepressants . The natural MAOH Harmalin is traditionally used by various South American Indian peoples in the drug preparation Ayahuasca .

further reading

  • DC Rowe: Biology and Crime. New York, Oxford University Press, 2007, ISBN 978-0-19-533009-0 .
  • RA Philibert, TD Gunter, SR Beach, GH Brody, A. Madan: MAOA methylation is associated with nicotine and alcohol dependence in women . In: Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B, no. 5 , July 2008, p. 565-570 , doi : 10.1002 / ajmg.b.30778 , PMID 18454435 .
  • DA Nielsen, V. Yuferov, S. Hamon et al .: Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts . In: Neuropsychopharmacology . tape 34 , no. 4 , March 2009, p. 867-873 , doi : 10.1038 / npp.2008.108 , PMID 18650805 .
  • MC Ho, CG Cherng, YP Tsai et al .: Chronic treatment with monoamine oxidase-B inhibitors decreases cocaine reward in mice . In: Psychopharmacology (Berl.) . tape 205 , no. 1 , July 2009, p. 141-149 , doi : 10.1007 / s00213-009-1524-5 , PMID 19343328 .
  • M. Rivera, B. Gutiérrez, E. Molina et al .: High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample . In: Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, no. 3 , April 2009, p. 395-402 , doi : 10.1002 / ajmg.b.30829 , PMID 18626920 .
  • AM Dlugos, AA Palmer, H. de Wit: Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans . In: J Neural Transm . tape 116 , no. 10 , October 2009, p. 1323-1334 , doi : 10.1007 / s00702-009-0281-2 , PMID 19657584 .

Individual evidence

  1. ↑ a b UniProt P21397 , UniProt P27338 .
  2. ↑ a b c N. P. Nair, SK Ahmed, NM Kin: Biochemistry and pharmacology of reversible inhibitors of MAO-A agents. Focus on moclobemide . In: Journal of psychiatry & neuroscience. JPN . tape 18 , no. 5 , November 1993, pp. 214-225 , PMID 7905288 , PMC 1188542 (free full text).
  3. ↑ Genes: MAOB monoamine oxidase B (human). Retrieved January 23, 2014 .
  4. ↑ AS Kalgutkar, DK Dalvie, N. Castagnoli, TJ Taylor: Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrate and inhibitor . In: Chem. Res. Toxicol. tape 14 , no. 9 , September 2001, p. 1139-1162 , doi : 10.1021 / tx010073b , PMID 11559028 .
  5. ^ Brunner syndrome.  In: Online Mendelian Inheritance in Man . (English).
  6. ^ Valerie Ross: Born into Debt: Gene Linked to Credit-Card Balances. In: Scientific American Mind. July 2010, accessed August 16, 2010 .
  7. ↑ Jan-Emmanuel De Neve, James H. Fowler: Credit Card Borrowing and the Monoamine Oxidase A (MAOA) Gene . In: Journal of Economic Behavior and Organization, Forthcoming . Rochester, NY February 27, 2014, doi : 10.2139 / ssrn.1457224 (English).
  8. ↑ JD Bremne, E. Vermetten: Stress and development: behavioral and biological consequences . In: Development and Psychopathology . tape 13 , no. 3 , 2001, p. 473-489 , PMID 11523844 .
  9. ↑ a b Avshalom Caspi, Joseph McClay, Terrie E. Moffitt, Jonathan Mill, Judy Martin, Ian W. Craig, Alan Taylor, Richie Poulton: Role of genotype in the cycle of violence in maltreated children . In: Science . tape 297 , no. 5582 , August 2002, p. 851-854 , doi : 10.1126 / science.1072290 , PMID 12161658 .
  10. ↑ G. Frazzetto, G. Di Lorenzo, V. Carola et al .: Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype . In: PLoS ONE . tape 2 , no. 5 , 2007, p. e486 , doi : 10.1371 / journal.pone.0000486 , PMID 17534436 , PMC 1872046 (free full text).
  11. ^ A. Gibbons: American Association of Physical Anthropologists meeting. Tracking the evolutionary history of a “warrior” gene . In: Science . tape 304 , no. 5672 , May 2004, p. 818 , doi : 10.1126 / science.304.5672.818a , PMID 15131284 .
  12. ^ D. Hall, M. Green, G. Chambers, R. Lea: Tracking the evolutionary history of the warrior gene in the South Pacific. 11th International Human Genetics Meeting, Brisbane, Australia; August 6-10; 2006. (Abstract) ( Memento from September 1, 2007 in the Internet Archive )
  13. ↑ a b Tony Merriman, Vicky Cameron: Risk-taking: behind the warrior gene story . In: The New Zealand Medical Journal . tape 120 , no. 1250 , 2007, p. U2440 , PMID 17339896 . - nzma.org.nz ( Memento of April 27, 2011 in the Internet Archive ).
  14. ↑ Maori 'warrior' gene linked to aggression . In: New Zealand Herald.
  15. ^ Peter Crampton, Chris Parkin: Warrior genes and risk-taking science . In: The New Zealand Medical Journal . tape 120 , no. 1250 , 2007, p. U2439 , PMID 17339895 . - nzma.org.nz ( Memento from May 23, 2010 in the Internet Archive ).
  16. ↑ Rod Lea, Geoffrey Chambers: Monoamine oxidase, addiction, and the "warrior" gene hypothesis . In: The New Zealand Medical Journal . tape 120 , no. 1250 , 2007, p. U2441 , PMID 17339897 . - nzma.org.nz ( Memento from April 16, 2010 in the Internet Archive ).
  17. ↑ GR Hook: ( Page no longer available , search in web archives: “Warrior genes” and the disease of being Māori. ) In: MAI Review. 2009, 2.@1@ 2Template: Dead Link / www.review.mai.ac.nz
  18. ↑ Yuji Kitaichi, Takeshi Inoue, Shin Nakagawa, Shuken Boku, Takeshi Izumi, Tsukasa Koyama: Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in beta-phenylethylamine . In: European Journal of Pharmacology . tape 637 , no. 1–3 , July 10, 2010, pp. 77-82 , doi : 10.1016 / j.ejphar.2010.04.014 , PMID 20406628 .
  19. ↑ Jens Asendorpf: Psychology of Personality. 4th, revised. and actual Edition. Springer, Heidelberg et al. 2007, ISBN 978-3-540-71684-6 , p. 186.