Editing Enzyme (section)

=== Involvement in disease ===
[[File:Phenylalanine hydroxylase mutations.svg|thumb|upright=2|alt= Ribbon diagram of phenylalanine hydroxylase with bound cofactor, coenzyme and substrate|In [[phenylalanine hydroxylase]] over 300 different mutations throughout the structure cause [[phenylketonuria]]. [[Phenylalanine]] substrate and [[tetrahydrobiopterin]] coenzyme in black, and [[Iron|Fe<sup>2+</sup>]] cofactor in yellow. ({{PDB|1KW0}})]]
[[File:Autosomal recessive inheritance for affected enzyme.png|thumb|upright=1.4|Hereditary defects in enzymes are generally inherited in an [[autosomal inheritance|autosomal]] fashion because there are more non-X chromosomes than X-chromosomes, and a [[recessive inheritance|recessive]] fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers.]]
{{see also|Genetic disorder}}

Since the tight control of enzyme activity is essential for [[homeostasis]], any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The malfunction of just one type of enzyme out of the thousands of types present in the human body can be fatal. An example of a fatal genetic disease due to enzyme insufficiency is [[Tay–Sachs disease]], in which patients lack the enzyme [[hexosaminidase]].<ref>{{cite journal | vauthors = Okada S, O'Brien JS | title = Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component | journal = Science | volume = 165 | issue = 3894 | pages = 698–700 | date = August 1969 | pmid = 5793973 | doi = 10.1126/science.165.3894.698 | s2cid = 8473726 | bibcode = 1969Sci...165..698O }}</ref><ref>{{cite web | title = Learning About Tay–Sachs Disease | url = http://www.genome.gov/10001220 | publisher = U.S. National Human Genome Research Institute | access-date = 1 March 2015 }}</ref>

One example of enzyme deficiency is the most common type of [[phenylketonuria]]. Many different single amino acid mutations in the enzyme [[phenylalanine hydroxylase]], which catalyzes the first step in the degradation of [[phenylalanine]], result in build-up of phenylalanine and related products. Some mutations are in the active site, directly disrupting binding and catalysis, but many are far from the active site and reduce activity by destabilising the protein structure, or affecting correct oligomerisation.<ref name=pmid10527663>{{cite journal | vauthors = Erlandsen H, Stevens RC | title = The structural basis of phenylketonuria | journal = Molecular Genetics and Metabolism | volume = 68 | issue = 2 | pages = 103–125 | date = October 1999 | pmid = 10527663 | doi = 10.1006/mgme.1999.2922 }}</ref><ref>{{cite journal | vauthors = Flatmark T, Stevens RC | title = Structural Insight into the Aromatic Amino Acid Hydroxylases and Their Disease-Related Mutant Forms | journal = Chemical Reviews | volume = 99 | issue = 8 | pages = 2137–2160 | date = August 1999 | pmid = 11849022 | doi = 10.1021/cr980450y }}</ref> This can lead to [[intellectual disability]] if the disease is untreated.<ref>{{cite book | title = Genes and Disease [Internet] | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK22253/ | chapter = Phenylketonuria | publisher = National Center for Biotechnology Information (US) | location = Bethesda (MD) | year = 1998–2015 }}</ref> Another example is [[pseudocholinesterase deficiency]], in which the body's ability to break down choline ester drugs is impaired.<ref>{{cite web | title = Pseudocholinesterase deficiency | url = http://ghr.nlm.nih.gov/condition/pseudocholinesterase-deficiency | publisher = U.S. National Library of Medicine | access-date = 5 September 2013 }}</ref>
Oral administration of enzymes can be used to treat some functional enzyme deficiencies, such as [[pancreatic insufficiency]]<ref>{{cite journal | vauthors = Fieker A, Philpott J, Armand M | title = Enzyme replacement therapy for pancreatic insufficiency: present and future | journal = Clinical and Experimental Gastroenterology | volume = 4 | pages = 55–73 | date = 2011 | pmid = 21753892 | pmc = 3132852 | doi = 10.2147/CEG.S17634 | doi-access = free }}</ref> and [[lactose intolerance]].<ref>{{cite journal | vauthors = Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M | title = Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment | journal = United European Gastroenterology Journal | volume = 1 | issue = 3 | pages = 151–159 | date = June 2013 | pmid = 24917953 | pmc = 4040760 | doi = 10.1177/2050640613484463 }}</ref>

Another way enzyme malfunctions can cause disease comes from [[germline mutation]]s in genes coding for [[DNA repair]] enzymes. Defects in these enzymes cause cancer because cells are less able to repair mutations in their [[genome]]s. This causes a slow accumulation of mutations and results in the [[carcinogenesis|development of cancers]]. An example of such a hereditary [[cancer syndrome]] is [[xeroderma pigmentosum]], which causes the development of [[skin cancer]]s in response to even minimal exposure to [[ultraviolet light]].<ref>{{cite journal | vauthors = Cleaver JE | title = Defective repair replication of DNA in xeroderma pigmentosum | journal = Nature | volume = 218 | issue = 5142 | pages = 652–656 | date = May 1968 | pmid = 5655953 | doi = 10.1038/218652a0 | s2cid = 4171859 | bibcode = 1968Natur.218..652C }}</ref><ref name="Andrews">{{cite book | vauthors = James WD, Elston D, Berger TG | title = Andrews' Diseases of the Skin: Clinical Dermatology | date = 2011 | publisher = Saunders/ Elsevier | location = London | isbn = 978-1437703146 | edition = 11th | page = 567 }}</ref>