Editing Kinase (section)

===Phosphatidylinositol kinases===
{{See also|Phosphatidylinositol phosphate kinases}}
[[File:PI3 Kinase.tif|thumb|upright=1|Insulin binding to its receptor leads allows PI3 kinase to dock at the membrane where it can phosphorylate PI lipids]]
Phosphatidylinositol kinases phosphorylate [[phosphatidylinositol]] species, to create species such as [[phosphatidylinositol 3,4-bisphosphate]] (PI(3,4)P<sub>2</sub>), [[phosphatidylinositol 3,4,5-trisphosphate]] (PIP<sub>3</sub>), and [[phosphatidylinositol 3-phosphate]] (PI3P). The kinases include [[phosphoinositide 3-kinase]] (PI3K), [[phosphatidylinositol-4-phosphate 3-kinase]], and [[phosphatidylinositol-4,5-bisphosphate 3-kinase]]. The phosphorylation state of phosphatidylinositol plays a major role in [[cellular signalling]], such as in the insulin signalling pathway, and also has roles in [[endocytosis]], [[exocytosis]] and other trafficking events.<ref>{{cite journal | vauthors = Sun Y, Thapa N, Hedman AC, Anderson RA | title = Phosphatidylinositol 4,5-bisphosphate: targeted production and signaling | journal = BioEssays | volume = 35 | issue = 6 | pages = 513–522 | date = June 2013 | pmid = 23575577 | pmc = 3882169 | doi = 10.1002/bies.201200171 }}</ref><ref>{{cite journal | vauthors = Heath CM, Stahl PD, Barbieri MA | title = Lipid kinases play crucial and multiple roles in membrane trafficking and signaling | journal = Histology and Histopathology | volume = 18 | issue = 3 | pages = 989–998 | date = July 2003 | pmid = 12792909 | doi = 10.14670/HH-18.989 }}</ref> Mutations in these kinases, such as PI3K, can lead to [[cancer]] or [[insulin resistance]].<ref>{{cite journal| vauthors = Cantley LC |title=PI 3-kinase and disease|journal=BMC Proceedings|year=2012|volume=6|issue=Suppl 3|pages=O2|doi=10.1186/1753-6561-6-S3-O2 |pmc=3395034 |doi-access=free}}</ref>

The kinase enzymes increase the rate of the reactions by making the inositol hydroxyl group more nucleophilic, often using the side chain of an amino acid residue to act as a general base and [[deprotonate]] the hydroxyl, as seen in the mechanism below.<ref name="PI" /> Here, a reaction between [[adenosine triphosphate|adenosine triphosphate (ATP)]] and phosphatidylinositol is coordinated. The end result is a phosphatidylinositol-3-phosphate as well as [[adenosine diphosphate|adenosine diphosphate (ADP)]]. The enzymes can also help to properly orient the ATP molecule, as well as the inositol group, to make the reaction proceed faster. Metal ions are often coordinated for this purpose.<ref name="PI" />

[[File:PI3kinase mechanism.png|thumb|upright=2.7|center|Mechanism of phosphatidylinositol-3 kinase. ATP and phosphatidylinositol react to form phosphatidylinositol-3-phosphate and ADP, with the help of general base ''B''.<ref name="PI">{{cite journal | vauthors = Miller S, Tavshanjian B, Oleksy A, Perisic O, Houseman BT, Shokat KM, Williams RL | title = Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34 | journal = Science | volume = 327 | issue = 5973 | pages = 1638–1642 | date = March 2010 | pmid = 20339072 | pmc = 2860105 | doi = 10.1126/science.1184429 | bibcode = 2010Sci...327.1638M }}</ref>]]