Enzyme (source code)
= Enzyme
{wiki}
An <enzyme> is a biological <catalyst>: it accelerates a <chemical reaction> and is regenerated after a successful catalytic cycle. Most <enzymes> are <proteins>, but catalytic <RNA> molecules, called <ribozymes>, also exist. Many reactions needed by a <biological cell> would proceed too slowly under its ordinary conditions without <enzymes>. See https://www.ncbi.nlm.nih.gov/books/NBK9921/[Cooper, The Cell: the central role of enzymes as biological catalysts].
The biological beauty is selective speed. A <biological cell> contains many possible <reactants>; its <enzymes> help determine which transformations happen on a useful timescale. In <metabolism>, one step's <reaction product> can become another step's <substrate>, so selective catalysts support an organized flow of material.
The <ribosome> is a striking biological example: the machinery that builds <proteins> has <RNA> at its catalytic centre. The complete <ribosome> contains both <RNA> and <proteins>, but its bond-forming <active site> is built from <RNA>. Structural evidence established this distinction in https://pubmed.ncbi.nlm.nih.gov/10937990/[Nissen et al., The structural basis of ribosome activity in peptide bond synthesis, Science 289, 920–930 (2000)].
Selection occurs at an <active site>, the region where <substrate> binding and catalytic chemistry take place. Shape and chemical interactions favour some <substrates> over others; binding can also reshape the <enzyme>, an <induced fit>. Recognition alone is insufficient: holding a <substrate> extremely tightly need not make it react quickly. Catalysis requires a favourable route through the <transition state>, the high-barrier configuration between <reactants> and <reaction products>. Positioning reactive groups and stabilizing this configuration relative to the bound <substrate> can lower that barrier. Specificity is often strong, but need not mean exactly one acceptable <substrate>. See https://www.ncbi.nlm.nih.gov/books/NBK9921/[Cooper, The Cell: mechanisms of enzymatic catalysis].
\Image[/enzyme-catalysis-energy.png]
{title=<Enzymes> lower reaction barriers while leaving the overall <Gibbs free energy> difference unchanged}
{description=Original illustrative profiles, with the free <enzyme> included in both endpoint states. The horizontal coordinate orders configurations along each route; it is neither elapsed time nor a measured distance. Actual catalytic mechanisms can have several intermediates and barriers.}
Read the diagram numerically. Its chosen <Gibbs free energies> are $0$ for the <reactants> and $-10\,\mathrm{kJ\,mol^{-1}}$ for the <reaction products>. The uncatalysed peak is $60\,\mathrm{kJ\,mol^{-1}}$, whereas the catalysed peak is $40\,\mathrm{kJ\,mol^{-1}}$. The forward free-energy barriers are therefore $60$ and $40\,\mathrm{kJ\,mol^{-1}}$; viewed from the <reaction products>, the reverse barriers are $70$ and $50\,\mathrm{kJ\,mol^{-1}}$. Both decrease by $20\,\mathrm{kJ\,mol^{-1}}$, while the endpoint difference stays $-10\,\mathrm{kJ\,mol^{-1}}$. These are constructed values, not measurements of a particular <enzyme>.
This separates <chemical kinetics> from <chemical equilibrium>. An <enzyme> changes how rapidly the system approaches <chemical equilibrium>; it does not change the <equilibrium constant> for the same overall <chemical reaction> under the same conditions. Faster catalysis therefore supplies no extra driving <energy>. In a <biological cell>, continuing supply of <reactants> and removal of <reaction products> can nevertheless sustain a net flow: the surroundings keep that system away from <chemical equilibrium>. See https://iubmb.qmul.ac.uk/kinetics/ek1t3.html[IUBMB, Symbolism and terminology in enzyme kinetics: basic definitions].
Some <enzymes> require a <cofactor (biochemistry)>, an additional nonprotein component such as a metal <ion> or a small organic molecule. Organic helpers are often called <coenzymes>; they can assist transfers that the <protein> alone cannot readily perform. The <cofactor (biochemistry)> may remain bound or exchange with the surroundings, depending on the system. A <coenzyme> can be chemically changed in one reaction and regenerated by another: regeneration of the <enzyme> does not mean every helper is unchanged in that individual reaction. Some <enzymes> need no additional <cofactor (biochemistry)>. See https://www.ncbi.nlm.nih.gov/books/NBK26911/[Alberts et al., Molecular Biology of the Cell: small molecules associated with proteins] and https://www.ncbi.nlm.nih.gov/books/NBK26838/[Alberts et al., activated carriers and their regeneration].
How much faster does adding <substrate> make a reaction? <Enzyme kinetics> gives a quantitative answer when a model's assumptions fit. For an illustrative reaction obeying <Michaelis-Menten kinetics>, use the <Michaelis-Menten equation> with <substrate> <concentration> $s$, limiting <reaction rate> $V_{\max}$ and <Michaelis constant> $K_M$. At $s/K_M=0.1$, substitution gives $v/V_{\max}=0.1/1.1=1/11\approx0.0909$. At $s/K_M=1$, it gives $1/2$; at $s/K_M=10$, it gives $10/11\approx0.9091$. Thus a hundredfold increase in <substrate> between the first and last examples yields only a tenfold increase in <reaction rate>.
\Image[/enzyme-substrate-saturation.png]
{title=Illustrative <Michaelis-Menten kinetics>: $s/K_M=0.1,1,10$ gives $v/V_{\max}=1/11,1/2,10/11$}
{description=Original normalized curve and computed examples, with a logarithmic concentration axis to separate the three values. The dashed upper line is a limiting rate approached at high <substrate> <concentration>, not reached at a finite concentration in this model.}
For a chosen $V_{\max}=110\,\mathrm{\mu M\,min^{-1}}$, those fractions mean <reaction rates> of $10$, $55$ and $100\,\mathrm{\mu M\,min^{-1}}$. Doubling <substrate> from $10K_M$ to $20K_M$ raises the normalized rate only from $10/11$ to $20/21\approx0.9524$, a relative increase of about $4.76\%$. In this simplest model, the catalytic machinery is already nearly fully occupied. Doubling the amount of active <enzyme> instead doubles $V_{\max}$ and the predicted <reaction rates> at fixed free <substrate> <concentration>, provided the other conditions are unchanged. This distinction helps decide whether additional <substrate> or additional catalytic capacity could improve throughput.
The interpretation has limits. The simplest <Michaelis-Menten kinetics> assumes a single <substrate>, fixed active <enzyme> amount, a suitable <quasi-steady-state approximation>, and initial measurements with negligible reverse reaction from accumulated <reaction product>. Substantial depletion, interacting binding sites, or inhibition by excess <substrate> can invalidate this model. Within it, $K_M$ is the <substrate> <concentration> giving half the limiting <reaction rate>; it is not generally the binding <dissociation constant> $K_d$. See https://iubmb.qmul.ac.uk/kinetics/ek1t3.html[IUBMB, enzyme kinetics: steady-state approximation and substrate dissociation] and https://iubmb.qmul.ac.uk/kinetics/ek4t6.html[IUBMB, Michaelis-Menten and non-Michaelis-Menten kinetics]. Measuring activity also requires specified <temperature>, <pH> and necessary <cofactor (biochemistry)> availability: a weak signal can reflect unsuitable conditions rather than little <enzyme>. See https://www.ncbi.nlm.nih.gov/books/NBK92007/[Brooks et al., Assay Guidance Manual: basics of enzymatic assays for HTS].
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