Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Monoamine Oxidase-A Deficiency (MAO-A)
Homo sapiens
Disease Pathway
Momoamine oxidase A (MAO-A) deficiency, or Brunner syndrome, is an X-linked recessive genetic disorder caused by a mutation in the MAOA gene that encodes for monoamine oxidase A. As such it is almost exclusively found in men. MAO-A is an enzyme that catalyzes the deamination of amines such as epinephrine, dopamine and tyramine, as part of the tyrosine metabolism pathway. In this disorder, some neurotransmitters such as serotonin and dopamine build up in the brain due to their inability to be properly metabolized. Since serotonin helps to regulate emotions and mood, with epinephrine and norepinephrine regulating stress, the unnecessary presence of the chemicals in the brain can lead to poor impulse control, aggression and other effects. The buildup of chemicals may also damage the brain, leading to a lower IQ in individuals with this disorder. In addition, foods containing the compounds that cannot be broken down, such as tyramine, can cause episodes of increased symptoms in the patients. In the subpathway that converts dopamine to homovanillic acid, there are two instances of MAO-A that are inactivated in this disorder, both in different branches. The first reaction converts dopamine to 3,4-dihydroxyphenylacetaldehyde, while the second converts 3-methoxytyramine to homovanillin. With the inactivation of MAO-A, 3-methoxytyramine builds up as there are no reactions that use it, and both of these paths lead to a decrease in the concentration of homovanillic acid, as there are no other reactions present that produce it. Another reaction, this time converting tyramine to homovanillin, is also prevented by the lack of MAO-A, which leads to an accumulation of tyramine in the body. In another branch of tyrosine metabolism, the absence of MAO-A prevents the oxidation of norepinephrine and epinephrine into 3,4-dihydroxymandelaldehyde. Its absence also prevents the oxidative deamination of metanephrine and normetanephrine into 3-methoxy-4-hydroxyphenylglycolaldehyde. As this is no longer produced, it leads to a decrease in the concentration of vanillylmandelic acid, which is produced from 3-methoxy-4-hydroxyphenylglycolaldehyde in a reaction catalyzed by aldehyde dehydrogenase.
References
Monoamine Oxidase-A Deficiency (MAO-A) References
Chen K, Holschneider DP, Wu W, Rebrin I, Shih JC: A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem. 2004 Sep 17;279(38):39645-52. doi: 10.1074/jbc.M405550200. Epub 2004 Jul 22.
Pubmed: 15272015
Palmer EE, Leffler M, Rogers C, Shaw M, Carroll R, Earl J, Cheung NW, Champion B, Hu H, Haas SA, Kalscheuer VM, Gecz J, Field M: New insights into Brunner syndrome and potential for targeted therapy. Clin Genet. 2016 Jan;89(1):120-7. doi: 10.1111/cge.12589. Epub 2015 Apr 19.
Pubmed: 25807999
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Yang YS, Wang CC, Chen BH, Hou YH, Hung KS, Mao YC: Tyrosine sulfation as a protein post-translational modification. Molecules. 2015 Jan 28;20(2):2138-64. doi: 10.3390/molecules20022138.
Pubmed: 25635379
Westmuckett AD, Thacker KM, Moore KL: Tyrosine sulfation of native mouse Psgl-1 is required for optimal leukocyte rolling on P-selectin in vivo. PLoS One. 2011;6(5):e20406. doi: 10.1371/journal.pone.0020406. Epub 2011 May 25.
Pubmed: 21633705
Ruzzene M, Donella-Deana A, Marin O, Perich JW, Ruzza P, Borin G, Calderan A, Pinna LA: Specificity of T-cell protein tyrosine phosphatase toward phosphorylated synthetic peptides. Eur J Biochem. 1993 Jan 15;211(1-2):289-95. doi: 10.1111/j.1432-1033.1993.tb19897.x.
Pubmed: 7678807
Honova E, Miller SA, Ehrenkranz RA, Woo A: Tyrosine transaminase: development of daily rhythm in liver of neonatal rat. Science. 1968 Nov 29;162(3857):999-1001. doi: 10.1126/science.162.3857.999.
Pubmed: 4387001
Bartesaghi S, Valez V, Trujillo M, Peluffo G, Romero N, Zhang H, Kalyanaraman B, Radi R: Mechanistic studies of peroxynitrite-mediated tyrosine nitration in membranes using the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester. Biochemistry. 2006 Jun 6;45(22):6813-25. doi: 10.1021/bi060363x.
Pubmed: 16734418
Goldstein S, Czapski G, Lind J, Merenyi G: Tyrosine nitration by simultaneous generation of (.)NO and O-(2) under physiological conditions. How the radicals do the job. J Biol Chem. 2000 Feb 4;275(5):3031-6. doi: 10.1074/jbc.275.5.3031.
Pubmed: 10652282
Radi R: Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res. 2013 Feb 19;46(2):550-9. doi: 10.1021/ar300234c. Epub 2012 Nov 16.
Pubmed: 23157446
Sherry DM, Kanan Y, Hamilton R, Hoffhines A, Arbogast KL, Fliesler SJ, Naash MI, Moore KL, Al-Ubaidi MR: Differential developmental deficits in retinal function in the absence of either protein tyrosine sulfotransferase-1 or -2. PLoS One. 2012;7(6):e39702. doi: 10.1371/journal.pone.0039702. Epub 2012 Jun 22.
Pubmed: 22745813
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings