Editing Catalase (section)

== Function ==

=== Molecular mechanism ===
While the complete mechanism of catalase is not currently known,<ref name=Boon_b/> the [[chemical reaction|reaction]] is believed to occur in two stages:

: H<sub>2</sub>O<sub>2</sub> + Fe(III)-E → H<sub>2</sub>O + O=Fe(IV)-E(.+)

: H<sub>2</sub>O<sub>2</sub> + O=Fe(IV)-E(.+) → H<sub>2</sub>O + Fe(III)-E + O<sub>2</sub><ref name=Boon_b>{{cite web |vauthors=Boon EM, Downs A, Marcey D | title = Proposed Mechanism of Catalase | work = Catalase: H<sub>2</sub>O<sub>2</sub>: H<sub>2</sub>O<sub>2</sub> Oxidoreductase: Catalase Structural Tutorial | url = http://biology.kenyon.edu/BMB/Chime/catalase/frames/cattx.htm#Proposed%20Mechanism%20of%20Catalase | access-date = 2007-02-11}}</ref>

Here Fe()-E represents the [[iron]] center of the [[heme]] group attached to the enzyme. Fe(IV)-E(.+) is a mesomeric form of Fe(V)-E, meaning the iron is not completely oxidized to +V, but receives some stabilising electron density from the heme ligand, which is then shown as a radical cation (.+).

As hydrogen peroxide enters the [[active site]], it does not interact with the [[amino acid]]s Asn148 ([[asparagine]] at position 148) and [[histidine|His75]], causing a [[proton]] (hydrogen [[ion]]) to transfer between the oxygen atoms. The free oxygen atom coordinates, freeing the newly formed water molecule and Fe(IV)=O. Fe(IV)=O reacts with a second hydrogen peroxide molecule to reform Fe(III)-E and produce water and oxygen.<ref name=Boon_b /> The reactivity of the iron center may be improved by the presence of the phenolate [[ligand]] of [[tyrosine|Tyr358]] in the fifth coordination position, which can assist in the [[oxidation]] of the Fe(III) to Fe(IV). The efficiency of the reaction may also be improved by the interactions of His75 and Asn148 with [[reaction intermediates]].<ref name=Boon_b /> The decomposition of hydrogen peroxide by catalase proceeds according to first-order kinetics, the rate being proportional to the hydrogen peroxide concentration.<ref>{{cite book | vauthors = Aebi H | title = Oxygen Radicals in Biological Systems | chapter = Catalase in vitro | series = Methods in Enzymology | volume = 105 | pages = 121–126 | date = 1984 | pmid = 6727660 | doi = 10.1016/S0076-6879(84)05016-3 | isbn = 9780121820053 }}</ref>

Catalase can also catalyze the oxidation, by [[hydrogen peroxide]], of various metabolites and toxins, including [[formaldehyde]], [[formic acid]], [[phenols]], [[acetaldehyde]] and [[alcohols]]. It does so according to the following reaction:

: H<sub>2</sub>O<sub>2</sub> + H<sub>2</sub>R → 2H<sub>2</sub>O + R

The exact mechanism of this reaction is not known.

Any heavy metal ion (such as copper cations in [[copper(II) sulfate]]) can act as a [[noncompetitive inhibitor]] of catalase.  However, "Copper deficiency can lead to a reduction in catalase activity in tissues, such as heart and liver."<ref>{{cite journal | vauthors = Hordyjewska A, Popiołek Ł, Kocot J | title = The many "faces" of copper in medicine and treatment | journal = Biometals | volume = 27 | issue = 4 | pages = 611–621 | date = August 2014 | pmid = 24748564 | pmc = 4113679 | doi = 10.1007/s10534-014-9736-5 }}</ref> Furthermore, the poison [[cyanide]] is a noncompetitive inhibitor<ref>{{cite journal | vauthors = Kremer ML | title = Nonstationary inhibition of enzyme action. The cyanide inhibition of catalase. | journal = The Journal of Physical Chemistry | date = April 1981 | volume = 85 | issue = 7 | pages = 835–839 | doi = 10.1021/j150607a021 }}</ref> of catalase at high concentrations of [[hydrogen peroxide]].<ref>{{cite journal | vauthors = Ogura Y, Yamazaki I | title = Steady-state kinetics of the catalase reaction in the presence of cyanide | journal = Journal of Biochemistry | volume = 94 | issue = 2 | pages = 403–408 | date = August 1983 | pmid = 6630165 | doi = 10.1093/oxfordjournals.jbchem.a134369 }}</ref>
[[Arsenate]] acts as an [[Enzyme activator|activator]].<ref>{{cite journal | vauthors = Kertulis-Tartar GM, Rathinasabapathi B, Ma LQ | title = Characterization of glutathione reductase and catalase in the fronds of two Pteris ferns upon arsenic exposure | journal = Plant Physiology and Biochemistry | volume = 47 | issue = 10 | pages = 960–965 | date = October 2009 | pmid = 19574057 | doi = 10.1016/j.plaphy.2009.05.009 | bibcode = 2009PlPB...47..960K }}</ref>  Three-dimensional [[protein structure]]s of the peroxidated catalase intermediates are available at the [[Protein Data Bank]].

=== Cellular role ===
Hydrogen peroxide is a harmful byproduct of many normal [[metabolism|metabolic]] processes; to prevent damage to cells and tissues, it must be quickly converted into other, less dangerous substances. To this end, catalase is frequently used by cells to rapidly catalyze the [[Chemical decomposition|decomposition]] of hydrogen peroxide into less-reactive [[gas]]eous [[oxygen]] and water molecules.<ref name=Gaetani_1996>{{cite journal | vauthors = Gaetani GF, Ferraris AM, Rolfo M, Mangerini R, Arena S, Kirkman HN | title = Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes | journal = Blood | volume = 87 | issue = 4 | pages = 1595–1599 | date = February 1996 | pmid = 8608252 | doi = 10.1182/blood.V87.4.1595.bloodjournal8741595 | doi-access = free }}</ref>

Mice genetically engineered to lack catalase are initially phenotypically normal.<ref name=Ho_2004>{{cite journal | vauthors = Ho YS, Xiong Y, Ma W, Spector A, Ho DS | title = Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury | journal = The Journal of Biological Chemistry | volume = 279 | issue = 31 | pages = 32804–32812 | date = July 2004 | pmid = 15178682 | doi = 10.1074/jbc.M404800200 | doi-access = free }}</ref> However, catalase deficiency in mice may increase the likelihood of developing [[obesity]], fatty liver,<ref name="pmid27939935">{{cite journal | vauthors = Heit C, Marshall S, Singh S, Yu X, Charkoftaki G, Zhao H, Orlicky DJ, Fritz KS, Thompson DC, Vasiliou V | title = Catalase deletion promotes prediabetic phenotype in mice | journal = Free Radical Biology & Medicine | volume = 103 | pages = 48–56 | date = February 2017 | pmid = 27939935 | pmc = 5513671 | doi = 10.1016/j.freeradbiomed.2016.12.011 }}</ref> and [[Diabetes mellitus type 2|type 2 diabetes]].<ref name="Góth_2012">{{cite journal | vauthors = Góth L, Nagy T | title = Acatalasemia and diabetes mellitus | journal = Archives of Biochemistry and Biophysics | volume = 525 | issue = 2 | pages = 195–200 | date = September 2012 | pmid = 22365890 | doi = 10.1016/j.abb.2012.02.005 }}</ref> Some humans have very low levels of catalase ([[acatalasia]]), yet show few ill effects.

The increased [[oxidative stress]] that occurs with [[ageing|aging]] in mice is alleviated by [[gene expression|over-expression]] of catalase.<ref name="pmid27575890">{{cite journal | vauthors = Selvaratnam J, Robaire B | title = Overexpression of catalase in mice reduces age-related oxidative stress and maintains sperm production | journal = Experimental Gerontology | volume = 84 | pages = 12–20 | date = November 2016 | pmid = 27575890 | doi = 10.1016/j.exger.2016.08.012 | s2cid = 2416413 }}</ref>  Over-expressing mice do not exhibit the age-associated loss of [[spermatozoon|spermatozoa]], [[testicle|testicular]] [[germ cell|germ]] and [[Sertoli cell]]s seen in wild-type mice.  Oxidative stress in [[wild-type]] mice ordinarily induces oxidative [[DNA damage (naturally occurring)|DNA damage]] (measured as [[8-Oxo-2'-deoxyguanosine|8-oxodG]]) in [[sperm]] with aging, but these damages are significantly reduced in aged catalase over-expressing mice.<ref name="pmid27575890" />   Furthermore, these over-expressing mice show no decrease in age-dependent number of pups per litter.  Overexpression of catalase targeted to mitochondria extends the lifespan of mice.<ref name="pmid15879174">{{cite journal | vauthors = Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS | title = Extension of murine life span by overexpression of catalase targeted to mitochondria | journal = Science | volume = 308 | issue = 5730 | pages = 1909–1911 | date = June 2005 | pmid = 15879174 | doi = 10.1126/science.1106653 | s2cid = 38568666 | bibcode = 2005Sci...308.1909S }}</ref>

In [[eukaryote]]s, catalase is usually located in a cellular [[organelle]] called the [[peroxisome]].<ref name="MBOC">{{cite book |vauthors=Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | title = Molecular Biology of the Cell | edition = 4th | publisher = Garland Science | location = New York | year = 2002 | chapter = Peroxisomes | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26858/ | isbn = 978-0-8153-3218-3 }}</ref> Peroxisomes in plant cells are involved in [[photorespiration]] (the use of oxygen and production of carbon dioxide) and symbiotic [[nitrogen fixation]] (the breaking apart of [[diatomic]] [[nitrogen]] (N<sub>2</sub>) to reactive nitrogen atoms). Hydrogen peroxide is used as a potent antimicrobial agent when cells are infected with a pathogen. Catalase-positive pathogens, such as ''[[Mycobacterium tuberculosis]]'', ''[[Legionella pneumophila]]'', and ''[[Campylobacter jejuni]]'', make catalase to deactivate the peroxide radicals, thus allowing them to survive unharmed within the [[Host (biology)|host]].<ref name="pmid12949187">{{cite journal | vauthors = Srinivasa Rao PS, Yamada Y, Leung KY | title = A major catalase (KatB) that is required for resistance to H2O2 and phagocyte-mediated killing in Edwardsiella tarda | journal = Microbiology | volume = 149 | issue = Pt 9 | pages = 2635–2644 | date = September 2003 | pmid = 12949187 | doi = 10.1099/mic.0.26478-0 | doi-access = free }}</ref>

Like [[alcohol dehydrogenase]], catalase converts ethanol to acetaldehyde, but it is unlikely that this reaction is physiologically significant.<ref name="lieb97">{{cite journal | vauthors = Lieber CS | title = Ethanol metabolism, cirrhosis and alcoholism | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 257 | issue = 1 | pages = 59–84 | date = January 1997 | pmid = 9028626 | doi = 10.1016/S0009-8981(96)06434-0 }}</ref>