Editing Metabolism (section)

==Xenobiotics and redox metabolism==
{{further|Xenobiotic metabolism|Drug metabolism|Alcohol metabolism|Antioxidant}}
All organisms are constantly exposed to compounds that they cannot use as foods and that would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called [[xenobiotic]]s.<ref>{{cite journal | vauthors = Testa B, Krämer SD | title = The biochemistry of drug metabolism--an introduction: part 1. Principles and overview | journal = Chemistry & Biodiversity | volume = 3 | issue = 10 | pages = 1053–101 | date = October 2006 | pmid = 17193224 | doi = 10.1002/cbdv.200690111 | s2cid = 28872968 }}</ref> Xenobiotics such as [[drug|synthetic drugs]], [[poison|natural poisons]] and [[antibiotic]]s are detoxified by a set of xenobiotic-metabolizing enzymes. In humans, these include [[cytochrome P450|cytochrome P450 oxidases]],<ref>{{cite journal | vauthors = Danielson PB | title = The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans | journal = Current Drug Metabolism | volume = 3 | issue = 6 | pages = 561–97 | date = December 2002 | pmid = 12369887 | doi = 10.2174/1389200023337054 }}</ref> [[Glucuronosyltransferase|UDP-glucuronosyltransferases]],<ref>{{cite journal | vauthors = King CD, Rios GR, Green MD, Tephly TR | title = UDP-glucuronosyltransferases | journal = Current Drug Metabolism | volume = 1 | issue = 2 | pages = 143–61 | date = September 2000 | pmid = 11465080 | doi = 10.2174/1389200003339171 }}</ref> and [[glutathione S-transferase|glutathione ''S''-transferases]].<ref>{{cite journal | vauthors = Sheehan D, Meade G, Foley VM, Dowd CA | title = Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily | journal = The Biochemical Journal | volume = 360 | issue = Pt 1 | pages = 1–16 | date = November 2001 | pmid = 11695986 | pmc = 1222196 | doi = 10.1042/0264-6021:3600001 }}</ref> This system of enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The modified water-soluble xenobiotic can then be pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III). In [[ecology]], these reactions are particularly important in microbial [[biodegradation]] of pollutants and the [[bioremediation]] of [[contaminated land]] and oil spills.<ref>{{cite journal | vauthors = Galvão TC, Mohn WW, de Lorenzo V | title = Exploring the microbial biodegradation and biotransformation gene pool | journal = Trends in Biotechnology | volume = 23 | issue = 10 | pages = 497–506 | date = October 2005 | pmid = 16125262 | doi = 10.1016/j.tibtech.2005.08.002 }}</ref> Many of these microbial reactions are shared with multicellular organisms, but due to the incredible diversity of types of microbes these organisms are able to deal with a far wider range of xenobiotics than multicellular organisms, and can degrade even [[persistent organic pollutant]]s such as [[organochloride]] compounds.<ref>{{cite journal | vauthors = Janssen DB, Dinkla IJ, Poelarends GJ, Terpstra P | title = Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities | journal = Environmental Microbiology | volume = 7 | issue = 12 | pages = 1868–82 | date = December 2005 | pmid = 16309386 | doi = 10.1111/j.1462-2920.2005.00966.x | url = https://pure.rug.nl/ws/files/3623678/2005EnvironMicrobiolJanssen.pdf | doi-access = free | bibcode = 2005EnvMi...7.1868J | access-date = 11 November 2019 | archive-date = 11 November 2019 | archive-url = https://web.archive.org/web/20191111195543/https://pure.rug.nl/ws/files/3623678/2005EnvironMicrobiolJanssen.pdf | url-status = live }}</ref>

A related problem for [[aerobic organism]]s is [[oxidative stress]].<ref name="Davies-1995">{{cite journal | vauthors = Davies KJ | title = Oxidative stress: the paradox of aerobic life | journal = Biochemical Society Symposium | volume = 61 | pages = 1–31 | year = 1995 | pmid = 8660387 | doi = 10.1042/bss0610001 }}</ref> Here, processes including [[oxidative phosphorylation]] and the formation of [[disulfide bond]]s during [[protein folding]] produce [[reactive oxygen species]] such as [[hydrogen peroxide]].<ref>{{cite journal | vauthors = Tu BP, Weissman JS | title = Oxidative protein folding in eukaryotes: mechanisms and consequences | journal = The Journal of Cell Biology | volume = 164 | issue = 3 | pages = 341–6 | date = February 2004 | pmid = 14757749 | pmc = 2172237 | doi = 10.1083/jcb.200311055 }}</ref> These damaging oxidants are removed by [[antioxidant]] metabolites such as [[glutathione]] and enzymes such as [[catalase]]s and [[peroxidase]]s.<ref name="Sies-1997">{{cite journal | vauthors = Sies H | title = Oxidative stress: oxidants and antioxidants | journal = Experimental Physiology | volume = 82 | issue = 2 | pages = 291–5 | date = March 1997 | pmid = 9129943 | doi = 10.1113/expphysiol.1997.sp004024 | s2cid = 20240552 | doi-access = free }}</ref><ref name="Vertuani-2004">{{cite journal | vauthors = Vertuani S, Angusti A, Manfredini S | title = The antioxidants and pro-antioxidants network: an overview | journal = Current Pharmaceutical Design | volume = 10 | issue = 14 | pages = 1677–94 | year = 2004 | pmid = 15134565 | doi = 10.2174/1381612043384655 | s2cid = 43713549 }}</ref>