Editing Dopamine (section)

===Degradation===
Dopamine is broken down into inactive [[metabolite]]s by a set of enzymes—[[monoamine oxidase]] (MAO), [[catechol-O-methyl transferase|catechol-''O''-methyl transferase]] (COMT), and [[aldehyde dehydrogenase]] (ALDH), acting in sequence.<ref name=Eisenhofer>{{cite journal | vauthors = Eisenhofer G, Kopin IJ, Goldstein DS | s2cid = 12825309 | title = Catecholamine metabolism: a contemporary view with implications for physiology and medicine | journal = Pharmacological Reviews | volume = 56 | issue = 3 | pages = 331–49 | date = September 2004 | pmid = 15317907 | doi = 10.1124/pr.56.3.1 }}</ref> Both [[protein isoform|isoforms]] of monoamine oxidase, [[Monoamine oxidase A|MAO-A]] and [[Monoamine oxidase B|MAO-B]], effectively metabolize dopamine.<ref name=Musacchio/> Different breakdown pathways exist but the main end-product is [[homovanillic acid]] (HVA), which has no known biological activity.<ref name=Eisenhofer/> From the bloodstream, homovanillic acid is filtered out by the kidneys and then excreted in the urine.<ref name=Eisenhofer/> The two primary metabolic routes that convert dopamine into HVA are:<ref>{{Cite book | vauthors = Zahoor I, Shafi A, Haq E | chapter = Pharmacological Treatment of Parkinson’s Disease: Figure 1: [Metabolic pathway of dopamine synthesis...] | veditors = Stoker TB, Greenland JC | title = Parkinson's Disease: Pathogenesis and Clinical Aspects [Internet]. | location = Brisbane (AU) | publisher = Codon Publications | date = December 2018 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK536726/figure/Ch7-f0001/ }}</ref>
* Dopamine → [[DOPAL]] → [[DOPAC]] → HVA&nbsp;– catalyzed by MAO, ALDH, and COMT respectively
* Dopamine → [[3-Methoxytyramine]] → HVA&nbsp;– catalyzed by COMT and MAO+ALDH respectively

In clinical research on schizophrenia, measurements of homovanillic acid in [[blood plasma|plasma]] have been used to estimate levels of dopamine activity in the brain. A difficulty in this approach however, is separating the high level of plasma homovanillic acid contributed by the metabolism of norepinephrine.<ref>{{cite journal | vauthors = Amin F, Davidson M, Davis KL | title = Homovanillic acid measurement in clinical research: a review of methodology | journal = Schizophrenia Bulletin | volume = 18 | issue = 1 | pages = 123–48 | year = 1992 | pmid = 1553492 | doi = 10.1093/schbul/18.1.123 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Amin F, Davidson M, Kahn RS, Schmeidler J, Stern R, Knott PJ, Apter S | title = Assessment of the central dopaminergic index of plasma HVA in schizophrenia | journal = Schizophrenia Bulletin | volume = 21 | issue = 1 | pages = 53–66 | date = 1995 | pmid = 7770741 | doi = 10.1093/schbul/21.1.53 | doi-access = free }}<!--|access-date=13 November 2015--></ref>

Although dopamine is normally broken down by an [[oxidoreductase]] enzyme, it is also susceptible to oxidation by direct reaction with oxygen, yielding [[quinone]]s plus various [[radical (chemistry)|free radicals]] as products.<ref name=Sulzer>{{cite journal | vauthors = Sulzer D, Zecca L | s2cid = 21892355 | title = Intraneuronal dopamine-quinone synthesis: a review | journal = Neurotoxicity Research | volume = 1 | issue = 3 | pages = 181–95 | date = February 2000 | pmid = 12835101 | doi = 10.1007/BF03033289 }}</ref> The rate of oxidation can be increased by the presence of [[ferric]] iron or other factors. Quinones and free radicals produced by autoxidation of dopamine can [[neurotoxicity|poison cells]], and there is evidence that this mechanism may contribute to the cell loss that occurs in [[Parkinson's disease]] and other conditions.<ref>{{cite journal | vauthors = Miyazaki I, Asanuma M | title = Dopaminergic neuron-specific oxidative stress caused by dopamine itself | journal = Acta Medica Okayama | volume = 62 | issue = 3 | pages = 141–50 | date = June 2008 | pmid = 18596830 | doi = 10.18926/AMO/30942 | url = http://www.lib.okayama-u.ac.jp/www/acta/pdf/62_3_141.pdf }}</ref>