Name: competitive vs noncompetitive inhibitors
Uploaded: 2025-10-23T11:48:34.000Z
Duration: 1 min 30 s
Channel: JoVE

特定の化学物質は酵素の機能を 抑制またはブロックすることで酵素の活性を制御します。酵素阻害物剤には2つの異なる形があります。競合的阻害剤と非競合阻害剤です。競合的阻害剤は酵素の特殊な基質に非常に類似しており 活性部位への結合が可能であり また、基質を結合から阻害します。この働きは基本的に、基質に結合可能な酵素の数を 減少します。その一方で、非競合阻害剤は 活性部位ではない、しかし依然として影響を及ぼす部位に結合し 例えば酵素の形を変えて 基質の活性部位への結合における 親和性を大きく減少し 酵素の正常な機能を妨げます。さらに、両タイプの阻害剤は特異的に 化学反応の割合に影響を及ぼします。標準的な酵素反応率であるコントロールと比較して 競合的阻害剤の反応は Vmax(最大反応速度)への到達速度が低下し 活性部位にアクセスするために 常に阻害剤を打ち負かすことが可能な 基質が十分に必要となることから より多くの基質の結合が求められます。これに対し、非競合阻害剤は 結合可能な酵素の数を減少させるため Vmaxに到達することができません。

「アルコール依存症の薬物療法-なぜ、何を、そしてなぜ」 Alimentary Pharmacology & Therapeutics 45, no. 7 (2017): 865-882.[<a href="https://doi.org/10.1111/apt.13965">ソース</a>]

酵素の阻害

Enzyme Inhibition

阻害剤とは、酵素に結合して酵素の活性を低下させる分子のことです。正常に機能している細胞では、酵素はさまざまな阻害剤によって制御されています。また、薬物やその他の毒素も酵素を阻害します。阻害剤には、酵素の活性部位に結合するものと、タンパク質構造上の他の部位に結合して酵素活性を阻害するものがあります。
 
 競合的阻害剤は、酵素の活性部位を占有し、基質を収容できなくします。その結果、競合阻害剤は酵素の初期反応速度を低下させますが、酵素の最大反応速度には影響を与えません。競合的阻害剤の一例として、慢性アルコール中毒の治療に使用されるジスルフィラムという薬があります。アルコールが摂取されると、通常はアセトアルデヒドに変換され、アセトアルデヒド脱水素酵素によってアセチル補酵素Aに変換されます。ジスルフィラムは、アセトアルデヒド脱水素酵素の活性部位に結合してこれを占有し、酵素がこの変換を行うことができなくなります。その結果、ジスルフィラムを服用した患者は、すぐに頭痛などの二日酔いのような症状が現れ、アルコール摂取量が減少します。
 
 非競合阻害剤は、酵素の活性部位から離れた別の部位に結合します。この部位はアロステリックサイトと呼ばれ、分子が結合すると活性部位の形状が変化し、酵素が基質との親和性を低下させます。非競合阻害剤は活性部位を占有しないため、基質が追加されても非競合阻害を克服することができず、酵素は最大の反応速度を得ることができません。
 
 阻害剤と酵素の間の共有結合は、いくつかの毒素の場合と同様に、通常は不可逆的です。通常、細胞内で活性化している調節性阻害剤の多くは、弱い相互作用によって酵素と相互作用します。このタイプの結合は可逆的で、代謝プロセスの調節に有用です。癌の細胞増殖を制御する酵素を競合的および非競合的に阻害する新しい分子の探索は、活発な研究分野です。

阻害剤は、酵素に結合することで酵素の活性を低下させる分子です。正常に機能している細胞では、酵素はさまざまな...

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生物学

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細胞プロセス

Metabolism

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KEY TERMS AND CONCEPTS

主要用語と概念

competitive vs noncompetitive inhibitors

Enzyme inhibitors are molecules that reduce enzyme activity by binding to enzymes. Cells use these inhibitors to help regulate normal enzyme function. Drugs and toxins can also block enzymes and change how they work.

Some inhibitors bind at the active site, which is the part of the enzyme where the substrate normally fits. Competitive inhibitors do this by occupying the active site and preventing the substrate from binding. If the substrate concentration becomes high enough, it can outcompete the inhibitor. For that reason, competitive inhibitors slow the initial reaction rate but do not change the enzyme’s maximum rate.

A clear example is disulfiram, a drug used to treat chronic alcoholism. Alcohol is normally converted to acetaldehyde and then to acetyl coenzyme A by acetaldehyde dehydrogenase. Disulfiram binds to the active site of acetaldehyde dehydrogenase and blocks this conversion. This causes hangover-like symptoms, such as headache, and helps decrease alcohol consumption.

Noncompetitive inhibitors bind at a different part of the enzyme. These binding sites are called allosteric sites. When a noncompetitive inhibitor binds, it changes the shape of the active site and lowers the enzyme’s affinity for the substrate. Extra substrate cannot overcome this effect, so the enzyme cannot reach its maximum reaction rate.

Some inhibitors form covalent bonds with enzymes. This binding is usually irreversible, as with some toxins. Most inhibitors that regulate metabolism in cells bind more weakly. That weak binding is reversible and helps control metabolic processes. Researchers also study enzyme inhibitors as possible treatments for cancers that involve cell growth.

Competitive vs Noncompetitive Inhibitors

what is metabolism?

Metabolism, Energy, and Cell Reactions

Metabolism is the set of chemical reactions that happen in a cell. It includes anabolism, which builds molecules, and catabolism, which breaks them down. These reactions help cells manage energy and keep life processes running. Cells use metabolism to turn food into energy, make cell parts, and remove waste products. Food stores potential energy in the bonds between atoms. Catabolic pathways break large food molecules into smaller ones and release that energy. Anabolic pathways use that energy...

first law of thermodynamics

Energy Flow in a Food Web

Energy flow in a food web shows the First Law of Thermodynamics in action. Energy cannot be created or destroyed. It can only change form as it moves through living things and the environment. Sunlight is the starting point. Plants capture radiant energy from the sun during photosynthesis and turn it into chemical energy stored in complex carbohydrates. At the same time, oxygen is released into the atmosphere. Herbivores eat the plants and use those sugars during digestion. The energy is...

second law of thermodynamics

Entropy in Food Web Energy Flow

The Second Law of Thermodynamics explains why entropy increases as energy moves through a system. Entropy means the amount of disorder in a system. Each time energy is transferred or transformed, some energy is lost as unusable heat. That heat can raise the motion of nearby molecules for a short time and make the surroundings less ordered and more random. This idea also appears in a food web. Primary producers, such as plants, take in energy from the sun and make food. During this process,...

kinetic energy

Motion as a Source of Energy

Kinetic energy is the energy of motion. It appears when an object is moving and can do work or cause change. A waterfall is one clear example. Water behind a dam has potential energy, but when it rushes downward, that moving water has kinetic energy. When the water reaches the bottom and stops moving, its energy can become potential energy again. Kinetic energy also shows up in living systems. Plants absorb light particles, called photons, which move very fast and help create chemical energy...

potential energy

Stored Energy in Motion and Bonds

Stored energy in motion and bonds is called potential energy. It depends on the structure of an object or the position of matter in space. Raising a kettlebell changes its location and increases its potential energy. A stretched rubber band also stores potential energy, which can later change into kinetic energy. Chemical bonds between atoms hold another form of stored energy called chemical energy. These bonds involve attractive forces, and that energy can change into other forms during a...

free energy

Gibbs Free Energy in Chemical Reactions

Gibbs free energy is a measure of useful energy that can be taken from a chemical reaction to do work. It is written as G and named for scientist Gibbs, who discovered it. This energy is what remains after entropy is considered. A reaction can either take in energy or release it. Reactions that absorb energy are called endergonic reactions. Reactions that release energy are called exergonic reactions. The direction of energy flow helps show which type of reaction is happening. Plants carry...

activation energy

How Catalysts Lower Reaction Barriers

Activation energy is the minimum energy a chemical reaction needs to keep going. When the activation energy is higher, the reaction usually happens more slowly. Adding heat can speed the reaction because molecules move faster and collide more often. As reactants collide, bonds break and the reaction moves through an uphill phase. That step creates the transition state, which is an unstable, high-energy state of the reactants. After that, new bonds form, products appear, and free energy is...

hydrolysis of atp

ATP Breakdown and Energy Release

ATP breakdown releases energy for cell work. Adenosine triphosphate, or ATP, can lose one or two phosphate groups when water is added. This hydrolysis reaction is exergonic, which means it releases energy that the cell can use. When one phosphate group is removed, ATP becomes ADP, or adenosine diphosphate. Inorganic phosphate is also released. ADP can then be hydrolyzed again to form AMP, or adenosine monophosphate, after a second phosphate group is removed. ATP has a clear structure. It is...

phosphorylation

Phosphorylation and Protein Control

Phosphorylation helps control how proteins work in cells. It is the addition or removal of phosphate groups, and it is the most common chemical change that regulates cellular processes. These changes can alter a protein’s structure, activity, stability, location inside the cell, and interactions with other proteins. During phosphorylation, protein kinases move the terminal phosphate group from ATP to a specific amino acid side chain on a target protein. The amino acids most often...

induced-fit model

How Enzymes Adjust to Their Substrates

Enzymes speed up many chemical reactions in cells. They are biological catalysts, so they increase reaction speed without being consumed or permanently changed. They do this by lowering the activation energy needed to turn reactants into products. Enzymes are proteins that usually work by binding to a substrate, which is the reactant molecule they act on. They show substrate specificity, meaning they bind only certain substrates. This specificity depends mainly on the shape and chemical...

enzyme kinetics

Substrate Effects on Enzyme Rates

Enzyme kinetics examines how enzymes change the rate of a reaction. Enzymes speed reactions by lowering the activation energy of the reactants. The reaction rate is the speed at which an enzyme turns reactants into products, and it can be affected by several factors, including the number of available reactants. Scientists often study enzyme kinetics in a test tube with a fixed amount of enzyme. When more substrate, or reactant, is added, the reaction rate increases because the enzyme can make...

enzyme inhibition

Enzyme inhibitors are molecules that reduce enzyme activity by binding to enzymes. Cells use these inhibitors to help regulate normal enzyme function. Drugs and toxins can also block enzymes and change how they work. Some inhibitors bind at the active site, which is the part of the enzyme where the substrate normally fits. Competitive inhibitors do this by occupying the active site and preventing the substrate from binding. If the substrate concentration becomes high enough, it can outcompete...

feedback inhibition

How Cells Control Product Buildup

Cells use enzymes to run biochemical reactions and make the products they need. These reactions are happening constantly, and enzymes speed them up so they happen fast enough to matter. Enzyme activity also has to be regulated. Cells need the right amounts of starting materials, intermediate metabolites, and final products. If these substances build up too much or drop too low, the cell can be harmed. That is why cells use control systems to keep metabolic levels balanced. One important...

allosteric regulation

Allosteric Control of Enzyme Speed

Allosteric control changes enzyme speed when a molecule binds to a site other than the active site. That alternate binding spot is called an allosteric site. An enzyme can have more than one allosteric site. This type of control can raise or lower enzyme activity. Many enzymes with allosteric control are metabolic enzymes. They help with the breakdown or the building of specific molecules in cells. In allosteric inhibition, the effector molecule causes a shape change that lowers the enzyme's...

cofactors and coenzymes

Enzyme Helpers: Metals, Vitamins, and More

Enzyme helpers are needed for many enzymes to work properly. These helpers fall into two groups: cofactors and coenzymes. Cofactors are metallic ions, while coenzymes are non-protein organic molecules. Both can be tightly bound to an enzyme or attach only when the substrate binds. Cofactors are common in mature proteins, appearing in about 30% of them. They are often added as the enzyme folds and help with catalytic activity. Magnesium is one important cofactor, and it is needed by more than...

key terms and concepts

Compare competitive and noncompetitive enzyme inhibitors, including active-site binding, allosteric effects, disulfiram, and how inhibitors regulate cells.

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Competitive vs Noncompetitive Inhibitors

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