Editing Enzyme (section)

==Kinetics==

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 | image1 = Enzyme mechanism 2.svg
 | alt1 = Schematic reaction diagrams for uncatalzyed (Substrate to Product) and catalyzed (Enzyme + Substrate to Enzyme/Substrate complex to Enzyme + Product)
 | caption1 = A chemical reaction mechanism with or without [[enzyme catalysis]]. The enzyme (E) binds [[substrate (chemistry)|substrate]] (S) to produce [[product (chemistry)|product]] (P).

 | image2 = Michaelis Menten curve 2.svg
 | alt2 = A two dimensional plot of substrate concentration (x axis) vs. reaction rate (y axis). The shape of the curve is hyperbolic. The rate of the reaction is zero at zero concentration of substrate and the rate asymptotically reaches a maximum at high substrate concentration.
 | caption2 = [[Michaelis–Menten kinetics|Saturation curve]] for an enzyme reaction showing the relation between the substrate concentration and reaction rate.
 }}

{{main|Enzyme kinetics}}

Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products.<ref>{{Cite book|title=Enzyme kinetics : principles and methods | vauthors = Bisswanger H | year = 2017 |isbn=9783527806461|edition= Third, enlarged and improved |location=Weinheim, Germany | publisher = Wiley-VCH |oclc=992976641}}</ref> The rate data used in kinetic analyses are commonly obtained from [[enzyme assay]]s. In 1913 [[Leonor Michaelis]] and [[Maud Leonora Menten]] proposed a quantitative theory of enzyme kinetics, which is referred to as [[Michaelis–Menten kinetics]].<ref>{{cite journal | vauthors = Michaelis L, Menten M | year = 1913 | title = Die Kinetik der Invertinwirkung | journal = Biochem. Z. | volume = 49 | pages = 333–369 | language = de | trans-title = The Kinetics of Invertase Action }}; {{cite journal | vauthors = Michaelis L, Menten ML, Johnson KA, Goody RS | title = The original Michaelis constant: translation of the 1913 Michaelis-Menten paper | journal = Biochemistry | volume = 50 | issue = 39 | pages = 8264–8269 | date = October 2011 | pmid = 21888353 | pmc = 3381512 | doi = 10.1021/bi201284u }}</ref> The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis–Menten complex in their honor. The enzyme then catalyzes the chemical step in the reaction and releases the product. This work was further developed by [[George Edward Briggs|G.&nbsp;E. Briggs]] and [[J.&nbsp;B.&nbsp;S. Haldane]], who derived kinetic equations that are still widely used today.<ref>{{cite journal | vauthors = Briggs GE, Haldane JB | title = A Note on the Kinetics of Enzyme Action | journal = The Biochemical Journal | volume = 19 | issue = 2 | pages = 338–339 | year = 1925 | pmid = 16743508 | pmc = 1259181 | doi = 10.1042/bj0190338 }}</ref>

Enzyme rates depend on [[Solution (chemistry)|solution]] conditions and substrate [[concentration]]. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex. At the maximum reaction rate (''V''<sub>max</sub>) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme.<ref name = "Stryer_2002"/>{{rp|8.4}}

''V''<sub>max</sub> is only one of several important kinetic parameters. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the [[Michaelis–Menten constant]] (''K''<sub>m</sub>), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate; generally, each enzyme has a characteristic ''K''<sub>M</sub> for a given substrate. Another useful constant is ''k''<sub>cat</sub>, also called the ''turnover number'', which is the number of substrate molecules handled by one active site per second.<ref name = "Stryer_2002"/>{{rp|8.4}}

The efficiency of an enzyme can be expressed in terms of ''k''<sub>cat</sub>/''K''<sub>m</sub>. This is also called the specificity constant and incorporates the [[rate constant]]s for all steps in the reaction up to and including the first irreversible step. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 10<sup>8</sup> to 10<sup>9</sup> (M<sup>−1</sup> s<sup>−1</sup>). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called ''[[catalytically perfect enzyme|catalytically perfect]]'' or ''kinetically perfect''. Example of such enzymes are [[triosephosphateisomerase|triose-phosphate isomerase]], [[carbonic anhydrase]], [[acetylcholinesterase]], [[catalase]], [[fumarase]], [[β-lactamase]], and [[superoxide dismutase]].<ref name = "Stryer_2002"/>{{rp|8.4.2}} The turnover of such enzymes can reach several million reactions per second.<ref name = "Stryer_2002"/>{{rp|9.2}} But most enzymes are far from perfect: the average values of <math>k_{\rm cat}/K_{\rm m}</math> and <math>k_{\rm cat}</math> are about <math> 10^5 {\rm s}^{-1}{\rm M}^{-1}</math> and <math>10 {\rm s}^{-1}</math>, respectively.<ref name="Bar-Even_2011">{{cite journal | vauthors = Bar-Even A, Noor E, Savir Y, Liebermeister W, Davidi D, Tawfik DS, Milo R | title = The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters | journal = Biochemistry | volume = 50 | issue = 21 | pages = 4402–4410 | date = May 2011 | pmid = 21506553 | doi = 10.1021/bi2002289 }}</ref>

Michaelis–Menten kinetics relies on the [[law of mass action]], which is derived from the assumptions of free [[diffusion]] and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of [[macromolecular crowding]] and constrained molecular movement.<ref>{{cite journal | vauthors = Ellis RJ | title = Macromolecular crowding: obvious but underappreciated | journal = Trends in Biochemical Sciences | volume = 26 | issue = 10 | pages = 597–604 | date = October 2001 | pmid = 11590012 | doi = 10.1016/S0968-0004(01)01938-7 }}</ref> More recent, complex extensions of the model attempt to correct for these effects.<ref>{{cite journal | vauthors = Kopelman R | title = Fractal reaction kinetics | journal = Science | volume = 241 | issue = 4873 | pages = 1620–1626 | date = September 1988 | pmid = 17820893 | doi = 10.1126/science.241.4873.1620 | s2cid = 23465446 | bibcode = 1988Sci...241.1620K }}</ref>