Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the enzyme prevents binding of the substrate and vice versa. HIV protease in a complex with the protease inhibitor ritonavir. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... For other uses, see Substrate. ...

Mechanism

In competitive inhibition, the inhibitor binds to the same active site as the normal enzyme substrate, without undergoing a reaction. The substrate molecule cannot enter the active site while the inhibitor is there, and the inhibitor cannot enter the site when the substrate is there. In this case, the maximum speed of the reaction is unchanged, while the apparent affinity of the substrate to the binding site is decreased (it means: the K_d dissociation constant is apparently increased). The change in K_m (Michaelis-Menten constant) is parallel to the alteration in K_d. Any given competitive inhibitor concentration can be overcome by increasing the substrate concentration in which case the substrate will outcompete the inhibitor in binding to the enzyme. The active site of an enzyme is the binding site where catalysis occurs. ...

Note that the inhibitor does not necessarily have to bind to the same active site that the substrate would bind to. As long as the binding of the inhibitor prevents the binding of the substrate (before it has done so), the inhibition mechanism is competitive. This can be observed by the binding of an inhibitor to a secondary site on the enzyme causing a conformational change in the structure such that the substrate cannot bind.

Equation

V_max remains the same because the presence of the inhibitor can be overcome by higher substrate concentrations.

where K_I is the inhibitors dissociation constant and [I] is the inhibitor concentration

Derivation

In the simplest case of a single-substrate enzyme obeying Michaelis-Menten kinetics, the typical scheme

E + S <==> ES ---> E + P

is modified to include binding of the inhibitor to the free enzyme:

EI + S <==> E + I + S <==> ES + I --> E + P + I

Note that the inhibitor does not bind to the ES complex and the substrate does not bind to the EI complex. It is generally assumed that this behavior is indicative of both compounds binding at the same site, but that is not strictly necessary. To derive the equation describing the kinetics, first assign microscopic rate constants to each step:
k₁ = E + S --> ES
k_-1 = ES --> E + S
k₂ = ES --> E + P
k₃ = E + I --> EI
k_-3 = EI --> E + I

Just as with the derivation of the Michaelis-Menten equation, assume that the system is at steady-state, that is that the concentration of each of the enzyme species is not changing.

=> dE/dt = dES/dt = dEI/dt = 0

Furthermore, the known total enzyme concentration is E_T = E + ES + EI, the velocity is measured under conditions in which the substrate and inhibitor concentrations do not change substantially and an insignificant amount of product has accumulated.
We can therefore set up a system of equations:
eq 1: E_T = E + ES + EI
eq 2: dE/dt = 0 = -_k1*E*S + k_-1*ES + k₂*ES -k₃*E*I + k_-3*EI
eq 3: dES/dt = 0 = k₁*E*S - k_-1*ES - k₂*ES
eq 4: dEI/dt = 0 = k₃*E*I - k_-3*EI

where S, I and E_T are known. The initial velocity is defined as v = dP/dt = k₂*ES, so we need to define the unknown "ES" in terms of the knowns S, I and E_T.

From eq 3, we can define E in terms of ES by rearranging to

k₁*E*S=(k_-1+k₂)*ES

Dividing by k₁*S gives E = (k_-1+k₂)*ES/(k₁*S)

As in the derivation of the Michaelis-Menten equation, the term (k_-1+k₂)/k₁ can be replaced by the macroscopic rate constant K_m:

eq 5: E = K_m*ES/S

Substituting eq 5 into eq 4, we have 0 = k₃*I*K_m*ES/S - k_-3*EI

Rearranging, we find that EI = k₃*I*K_m*ES/(S*k_-3).

At this point, we can define the dissociation constant for the inhibitor as K_i = k_-3/k₃, giving

eq 6: EI = I*K_m*ES/(S*K_i)

At this point, substitute eq 5 and eq 6 into eq 1:

E_T = K_m*ES/S + ES + I*K_m*ES/(S*K_i)

Rearranging to solve for ES, we find E_T = ES*(K_m/S + 1 + I*K_m/(S*K_i))= (K_m*K_i+S*K_i+I*K_m)/(S*K_i)

=> eq 7: ES = E_T*S*K_i/(K_m*K_i+S*K_i+I*K_m)

Returning to our expression for v, we now have v = k₂*ES = k₂*E_T*S*K_i/(K_m*K_i+S*K_i+I*K_m)

Rearranging and replacing k₂ with k_cat, we have v = k_cat*E_T*S/(K_m + S + K_m*(I/K_i))

Finally, we can replace k_cat*E_T with V_max and combine terms to yield the conventional form:

v = V_max*S/(S + K_m*(1 + I/K_i))

Pharmacology (in Greek: pharmakon (φάρμακον) meaning drug, and lego (λέγω) to tell (about)) is the study of how drugs interact with living organisms to produce a change in function. ... HIV protease in a complex with the protease inhibitor ritonavir. ... Uncompetitive inhibition takes place when an enzyme inhibitor binds only to the complex formed between the enzyme and the substrate (the E-S complex). ... Non-competitive inhibition is a type of inhibition that reduces the maximum rate of a chemical reaction (Vmax) without changing the apparent binding affinity of the enzyme for the substrate (Km). ... Suicide inhibition, also known as suicide inactivation and mechanism-based inactivation, is a form of irreversible enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms a complex with it during the normal catalysis reaction. ... Mixed inhibition refers to a combination of two different types of reversible enzyme inhibition--competitive inhibition and uncompetitive inhibition. ... A cholinesterase inhibitor or anticholinesterase is a chemical that inhibits a cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter acetylcholine. ... Aromatase inhibitors (AI) are a class of drugs used in the treatment of breast cancer in post- menopausal women. ... Wikipedia does not yet have an article with this exact name. ... Integrase inhibitors are a class of antiretroviral drug developed for the treatment of HIV infection. ... A kinase inhibitor is a type of enzyme inhibitor which specifically blocks the action of protein kinase. ... A Lipoxygenase inhibitor is a drug which slows down or stops the action of the lipoxygenase enzyme. ... MAOI redirects here. ... This article needs to be cleaned up to conform to a higher standard of quality. ... A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). ... In biology and biochemistry, protease inhibitors are molecules that inhibit the function of peptidases (old name: protease, hence the term protease inhibitor). ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... Trypsin inhibitors are chemicals that reduce the bio-availability of trypsin, an amino acid essential to nutrition of many animals, including humans. ...

see also

• Schild regression for ligand receptor inhibition
• Non-competitive inhibition