Editing Hexokinase (section)

==Types of mammalian hexokinase==
There are four important [[mammal]]ian hexokinase isozymes ({{EC number|2.7.1.1}}) that vary in subcellular locations and kinetics with respect to different substrates and conditions, and physiological function. They were designated hexokinases A, B, C, and D on the basis of their electrophoretic mobility.<ref>{{cite journal | doi= 10.1016/0006-291X(64)90038-5 | title = Multiple molecular forms of ATP:hexose 6-phosphotransferase from rat liver | last1=González | first1 = C. | last2 = Sánchez  | first2 = R. | last3 = Ureta | first3 = T. | last4 = Niemeyer | first4 = H. |journal = Biochemical and Biophysical Research Communications  | volume= 16 | number = 4 | year=1964 | pages=347-352| pmid = 5871820 }}</ref> The alternative names hexokinases I, II, III, and IV (respectively)<ref>{{cite journal | doi= 10.1016/0006-291X(65)90472-9 |journal = Biochemical and Biophysical Research Communications  | last1 = Katzen  | first1 = H. M. | last2 = Sodermann |first2 = D. D.  | last3 = Nitowsky | first3 = H. M. | volume=19  | number = 3 | pages = 377–382 | title = Kinetic and electrophoretic evidence for multiple forms of glucose–ATP phosphotransferase activity from human cell cultures and rat liver|year = 1965 |pmid = 14317406 }}</ref> proposed later are widely used.

===Hexokinases I, II, and III===
Hexokinases I, II, and III are referred to as low-''K''<sub>m</sub> isoenzymes because of a high affinity for glucose (below 1 mM). Hexokinases I and II follow [[Michaelis-Menten kinetics]] at physiological concentrations of substrates.{{citation needed|date=April 2016}} All three are strongly [[Enzyme inhibitor|inhibited]] by their product, [[glucose-6-phosphate]]. [[Molecular mass]]es are around 100 kDa. Each consists of two similar 50kDa halves, but only in hexokinase II do both halves have functional active sites.

* Hexokinase I/A is found in all mammalian tissues, and is considered a "housekeeping enzyme," unaffected by most physiological, hormonal, and metabolic changes.
* Hexokinase II/B constitutes the principal regulated isoenzyme in many cell types and is increased in many cancers. It is the hexokinase found in muscle and heart. Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP.<ref>{{cite web|url=https://www.uniprot.org/uniprot/P52789#subcellular_location|website=uniprot.org|title=Hexokinase data on Uniprot}}</ref> The relative specific activity of hexokinase II increases with pH at least in a pH range from 6.9 to 8.5.<ref name = "Šimčíková_2019">{{cite journal | vauthors = Šimčíková D, Heneberg P | title = Identification of alkaline pH optimum of human glucokinase because of ATP-mediated bias correction in outcomes of enzyme assays | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 11422 | date = August 2019 | pmid = 31388064 | pmc = 6684659 | doi = 10.1038/s41598-019-47883-1 | bibcode = 2019NatSR...911422S }}</ref>
* Hexokinase III/C is substrate-inhibited by glucose at physiological concentrations. Little is known about the regulatory characteristics of this isoenzyme.

===Hexokinase IV ("glucokinase")===
{{Main|Glucokinase}}

Mammalian hexokinase IV, also referred to as [[glucokinase]], differs from other hexokinases in kinetics and functions.

The location of the [[phosphorylation]] on a subcellular level occurs when glucokinase translocates between the [[cytoplasm]] and [[Cell nucleus|nucleus]] of [[liver]] cells.  Glucokinase can only phosphorylate glucose if the concentration of this substrate is high enough; it does not follow [[Michaelis–Menten kinetics|Henri–Michaelis–Menten kinetics]], and has no ''K''<sub>m</sub>; It is half-saturated at glucose concentrations 100 times higher than those of hexokinases I, II, and III.

Hexokinase IV is monomeric, about 50kDa, displays positive cooperativity with glucose, and is not [[allosterically]] inhibited by its product, glucose-6-phosphate.<ref name="Cardenas1998" />

Hexokinase IV is present in the [[liver]], [[pancreas]], [[hypothalamus]], [[small intestine]], and perhaps certain other [[neuroendocrine]] cells, and plays an important regulatory role in [[carbohydrate metabolism]]. In the [[beta cell|β cells]] of the pancreatic [[islets of Langerhans|islet]]s, it serves as a glucose sensor to control [[insulin]] release, and similarly controls [[glucagon]] release in the [[alpha cell|α cells]]. In [[hepatocyte]]s of the liver, glucokinase responds to changes of ambient glucose levels by increasing or reducing glycogen synthesis.