Editing Bilirubin (section)

== Function ==
Bilirubin is created by the activity of [[biliverdin reductase]] on [[biliverdin]], a green tetrapyrrolic bile pigment that is also a product of heme [[catabolism]]. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin,<ref name="PMID 3029864">{{cite journal | vauthors = Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN | title = Bilirubin is an antioxidant of possible physiological importance | journal = Science | volume = 235 | issue = 4792 | pages = 1043–6 | date = February 1987 | pmid = 3029864 | doi = 10.1126/science.3029864 | bibcode = 1987Sci...235.1043S }}</ref> has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.<ref name="pmid12456881">{{cite journal | vauthors = Baranano DE, Rao M, Ferris CD, Snyder SH | title = Biliverdin reductase: a major physiologic cytoprotectant | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 25 | pages = 16093–8 | date = December 2002 | pmid = 12456881 | pmc = 138570 | doi = 10.1073/pnas.252626999 | bibcode = 2002PNAS...9916093B | jstor = 3073913 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH | title = Bilirubin and glutathione have complementary antioxidant and cytoprotective roles | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 13 | pages = 5171–6 | date = March 2009 | pmid = 19286972 | pmc = 2664041 | doi = 10.1073/pnas.0813132106 | bibcode = 2009PNAS..106.5171S | jstor = 40455167 | doi-access = free }}</ref> Consistent with this, animal studies suggest that eliminating bilirubin results in endogenous oxidative stress.<ref name="PMID 29195835">{{cite journal | vauthors = Chen W, Maghzal GJ, Ayer A, Suarna C, Dunn LL, Stocker R | title = Absence of the biliverdin reductase-a gene is associated with increased endogenous oxidative stress | journal = Free Radical Biology & Medicine | volume = 115 | pages = 156–165 | date = February 2018 | pmid = 29195835 | doi = 10.1016/j.freeradbiomed.2017.11.020 | s2cid = 25089098 }}</ref> Bilirubin's antioxidant activity may be particularly important in the brain, where it prevents excitotoxicity and neuronal death by scavenging superoxide during N-methyl-D-aspartic acid neurotransmission.<ref name="PMID 31353321">{{cite journal | vauthors = Vasavda C, Kothari R, Malla AP, Tokhunts R, Lin A, Ji M, Ricco C, Xu R, Saavedra HG, Sbodio JI, Snowman AM, Albacarys L, Hester L, Sedlak TW, Paul BD, Snyder SH | display-authors = 6 | title = Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide | journal = Cell Chemical Biology | volume = 26 | issue = 10 | pages = 1450–1460.e7 | date = October 2019 | pmid = 31353321 | doi = 10.1016/j.chembiol.2019.07.006 | pmc = 6893848 | doi-access = free }}</ref>