Editing Enzyme (section)

=== Control of activity ===

There are five main ways that enzyme activity is controlled in the cell.<ref name = "Stryer_2002" />{{rp|30.1.1}}

====Regulation====
Enzymes can be either [[enzyme activator|activated]] or [[enzyme inhibitor|inhibited]] by other molecules. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a [[negative feedback|negative feedback mechanism]], because the amount of the end product produced is regulated by its own concentration.<ref name = "Suzuki_2015_8"/>{{rp|141–48}} Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps with effective allocations of materials and energy economy, and it prevents the excess manufacture of end products. Like other [[homeostasis|homeostatic devices]], the control of enzymatic action helps to maintain a stable internal environment in living organisms.<ref name = "Suzuki_2015_8"/>{{rp|141}}

====Post-translational modification====
Examples of [[post-translational modification]] include [[phosphorylation]], [[myristoylation]] and [[glycosylation]].<ref name = "Suzuki_2015_8">{{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 | chapter = Chapter 8: Control of Enzyme Activity | pages = 141–69 }}</ref>{{rp|149–69}} For example, in the response to [[insulin]], the [[phosphorylation]] of multiple enzymes, including [[glycogen synthase]], helps control the synthesis or degradation of [[glycogen]] and allows the cell to respond to changes in [[blood sugar]].<ref name = "Doble_2003">{{cite journal | vauthors = Doble BW, Woodgett JR | title = GSK-3: tricks of the trade for a multi-tasking kinase | journal = Journal of Cell Science | volume = 116 | issue = Pt 7 | pages = 1175–1186 | date = April 2003 | pmid = 12615961 | pmc = 3006448 | doi = 10.1242/jcs.00384 }}</ref> Another example of post-translational modification is the cleavage of the polypeptide chain. [[Chymotrypsin]], a digestive protease, is produced in inactive form as [[chymotrypsinogen]] in the [[pancreas]] and transported in this form to the [[stomach]] where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a [[zymogen]]<ref name = "Suzuki_2015_8"/>{{rp|149–53}} or proenzyme.

====Quantity====
Enzyme production ([[Transcription (genetics)|transcription]] and [[Translation (genetics)|translation]] of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of [[regulation of gene expression|gene regulation]] is called [[enzyme induction]]. For example, bacteria may become [[antibiotic resistance|resistant to antibiotics]] such as [[penicillin]] because enzymes called [[beta-lactamase]]s are induced that hydrolyse the crucial [[Beta-lactam|beta-lactam ring]] within the penicillin molecule.<ref name="pmid8452343">{{cite journal | vauthors = Bennett PM, Chopra I | title = Molecular basis of beta-lactamase induction in bacteria | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 2 | pages = 153–158 | date = February 1993 | pmid = 8452343 | pmc = 187630 | doi = 10.1128/aac.37.2.153 }}</ref> Another example comes from enzymes in the [[liver]] called [[cytochrome P450 oxidase]]s, which are important in [[drug metabolism]]. Induction or inhibition of these enzymes can cause [[drug interaction]]s.<ref name = "Skett_Gibson_2001">{{cite book |vauthors=Skett P, Gibson GG | title = Introduction to Drug Metabolism | date = 2001 | publisher = Nelson Thornes Publishers | location = Cheltenham, UK | isbn = 978-0748760114 | pages = 87–118 | edition = 3 | chapter = Chapter 3: Induction and Inhibition of Drug Metabolism }}</ref> Enzyme levels can also be regulated by changing the rate of enzyme [[catabolism|degradation]].<ref name="Stryer_2002" />{{rp|30.1.1}} The opposite of enzyme induction is [[enzyme repression]].

====Subcellular distribution====
Enzymes can be compartmentalized, with different metabolic pathways occurring in different [[cellular compartment]]s. For example, [[fatty acid]]s are synthesized by one set of enzymes in the [[cytosol]], [[endoplasmic reticulum]] and [[golgi apparatus|Golgi]] and used by a different set of enzymes as a source of energy in the [[mitochondrion]], through [[β-oxidation]].<ref>{{cite journal | vauthors = Faergeman NJ, Knudsen J | title = Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling | journal = The Biochemical Journal | volume = 323 | issue = Pt 1 | pages = 1–12 | date = April 1997 | pmid = 9173866 | pmc = 1218279 | doi = 10.1042/bj3230001 }}</ref> In addition, [[protein targeting|trafficking]] of the enzyme to different compartments may change the degree of [[protonation]] (e.g., the neutral [[cytoplasm]] and the acidic [[lysosome]]) or oxidative state (e.g., oxidizing [[periplasm]] or reducing [[cytoplasm]]) which in turn affects enzyme activity.<ref name = "Suzuki_2015_4">{{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 | chapter = Chapter 4: Effect of pH, Temperature, and High Pressure on Enzymatic Activity | pages = 53–74 }}</ref> In contrast to partitioning into membrane bound organelles, enzyme subcellular localisation may also be altered through polymerisation of enzymes into macromolecular cytoplasmic filaments.<ref>{{cite journal | vauthors = Noree C, Sato BK, Broyer RM, Wilhelm JE | title = Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster | journal = The Journal of Cell Biology | volume = 190 | issue = 4 | pages = 541–551 | date = August 2010 | pmid = 20713603 | pmc = 2928026 | doi = 10.1083/jcb.201003001 }}</ref><ref>{{cite journal | vauthors = Aughey GN, Liu JL | title = Metabolic regulation via enzyme filamentation | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 51 | issue = 4 | pages = 282–293 | date = 2015 | pmid = 27098510 | pmc = 4915340 | doi = 10.3109/10409238.2016.1172555 }}</ref>

====Organ specialization====
In [[multicellular]] [[eukaryote]]s, cells in different [[organ (anatomy)|organs]] and [[tissue (biology)|tissues]] have different patterns of [[gene expression]] and therefore have different sets of enzymes (known as [[isozyme]]s) available for metabolic reactions. This provides a mechanism for regulating the overall metabolism of the organism. For example, [[hexokinase]], the first enzyme in the [[glycolysis]] pathway, has a specialized form called [[glucokinase]] expressed in the liver and [[pancreas]] that has a lower [[affinity (pharmacology)|affinity]] for glucose yet is more sensitive to glucose concentration.<ref>{{cite journal | vauthors = Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y | title = Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase | journal = Structure | volume = 12 | issue = 3 | pages = 429–438 | date = March 2004 | pmid = 15016359 | doi = 10.1016/j.str.2004.02.005 | doi-access = free }}</ref> This enzyme is involved in sensing [[blood sugar]] and regulating insulin production.<ref>{{cite journal | vauthors = Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P | title = Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus | journal = The New England Journal of Medicine | volume = 328 | issue = 10 | pages = 697–702 | date = March 1993 | pmid = 8433729 | doi = 10.1056/NEJM199303113281005 | doi-access = free }}</ref>