Enzyme

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Many chemical reactions occur within biological cells. Most of these reactions happen too slowly to be biologically relevant. A special class of protein molecules called enzymes (in ferment) speed up such reactions. Chemical reactions need a certain amount of activation energy to take place. Enzymes can increase reaction speed by allowing a different reaction path with a lower activation energy (Fig. 1), making it easier for the reaction to occur. Enzymes are large proteins that catalyze (accelerate) chemical reactions. They are essential for the function of cells. Enzymes are very specific to the reactions they catalyze, and the chemicals (substrates) that are involved in the reactions. Substrates fit their enzymes like a key fits its lock (Fig. 2). Many enzymes are composed of several proteins that act together as a unit. Most parts of an enzyme have regulatory or structural purposes. The catalyzed reaction takes place in only a small part of the enzyme called the active site.

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Figure 1: Diagram of a catalytic reaction, showing the energy needed (E) against the time (t). The substrates (A and B) need a large amount of energy (E1) to reach the intermediate state A...B, which then reacts to the end product (AB). The enzyme (E) creates an "environment" in which A and B can reach the intermediate state (A...E...B) more easily, reducing the amount of energy needed (E2). As a result, the reaction is more likely to take place, thus improving the reaction speed.

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Figure 2: An enzyme (E) catalyzes two substrates (S1 and S2) to one product (P). Enzymes can perform up to several million catalytic reactions per second. To determine the maximum speed of a given enzyme, the substrate concentration is increased until a constant speed is achieved (Fig. 3). This is the maximum speed (Vmax) of the enzyme. In this state, all enzymes are saturated with substrate. This was proposed in 1913 by Leonor Michaelis and Maud Menten. Since the substrate concentration at Vmax cannot be measured exactly, enzymes are characterized by the substrate concentration that a given enzyme can catalyze with half its maximum speed. This substrate concentration is called Michaelis-Menten constant (KM). Most enzymes do obey Michaelis-Menten kinetics.

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Figure 3: Diagram of reaction speed and Michaelis-Menten constant. The speed V means the number of reactions per second that are catalyzed by an enzyme. With increasing substrate concentration [S], the enzyme is asymptotically approaching its maximum speed Vmax, but never actually reaching it. Because of that, no [S] for Vmax can be given. Instead, the characteristic value for the enzyme is defined by the substrate concentration at its half-maximum speed (Vmax/2). This KM value is also called Michaelis-Menten constant.

There are a number of factors that can influence the reaction speed, catalytic activity, and specificity of an enzyme. Apart from de novo synthesis (the production of more enzymes to increase catalysis rates), basic factors of the medium inside the cell like pH value or temperature can denaturate an enzyme (alter its shape) so that it can no longer function. More specific regulation is possible by posttranslational modification (e.g., phosphorylation) of the enzyme or by adding cofactors like metal ions or organic molecules (e.g. NAD+, FAD, CoA or vitamins) that interact with the enzyme. Allosteric enzymes are composed of several subunits (proteins) that interact with each other and thus influence each other's catalytic activity. In addition to that, enzymes can be regulated by competitive inhibitors (Fig. 4) and uncompetitive inhibitors and activators (Fig. 5). Inhibitors and activators are often used as medicines, but they can also be poisonous.

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Figure 4: Competitive inhibition.
A competitive inhibitor (I) fits the enzyme (E) as good as its real substrate (S), sometimes even better. The inhibitor (I) takes the place of the substrate (S) in the active center, but cannot undergo the catalytic reaction, thus inhibiting the enzyme (E) from catalyzing a substrate (S) molecule. Some inhibitors (I) build covalent bonds with the enzyme (E), deactivating it permanently (suicide inhibitors).

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Figure 5: Uncompetitive inhibition.
Uncompetitive inhibitors/activators (I) do not bind at the active center, but at other parts of the enzyme (E) that can be far away from the substrate (S) binding site. By changing the conformation (the three-dimensional structure) of the enzyme (E), they disable or enable the ability of the enzyme (E) to bind its substrate (S) and catalyze the desired reaction.

Several enzymes can work together in a specific order, creating metabolic pathways (e.g., the Citric Acid cycle, a series of enzymatic reactions in the cells of aerobic organisms, important in cellular respiration). In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. The end product(s) of such a pathway are often uncompetitive inhibitors (Fig. 5) for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathway (Fig. 6).

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Figure 6: Common feedback inhibition mechanisms.

  1. The basic feedback inhibition mechanism, where the product (P) inhibits the committed step (A->B).
  2. Sequential feedback inhibition.' The end products P1 and P2 inhibit the first committed step of their individual pathway (C->D or C->F). If both products are present in abundance, all pathways fron C are blocked. This leads to a buildup of C, which in turn inhibits the first common committed step A->B.
  3. Enzyme multiplicity. Each end product inhibits both the first individual committed step and one of the enzymes performing the first common commited step.
  4. Concerted feedback inhibition. Each end product inhibits the first individual committed step. Together, they inhibit the first common committed step.
  5. Cumultative feedback inhibition. Each end product inhibits the first individual committed step. Also, each end product partially inhibits the first common committed step.

Enzymes are essential to living organisms, and a malfunction of even a single enzyme can lead to severe or lethal sickness. An example for a sickness caused by an enzyme malfunction in humans is phenylketonuria. The enzyme phenylalanine hydroxylase that usually catalyzes the essential amino acid phenylalanine into tyrosine does not work, resulting in a buildup of phenylalanine that leads to mental retardation. Enzymes in the human body can also be influenced by inhibitors in either good or bad ways. Aspirin, for example, inhibits an enzyme that produces prostaglandins (inflammation messengers), thus suppressing pain. Carbon monoxide (CO) is a competitive inhibitor (Fig. 4) for oxygen (O2) when binding to hemoglobin. Carbon monoxide has a 230-270x affinity for hemoglobin than oxygen and therefore displaces oxygen. Enzymes are also used in everyday products such as biological washing detergents.

By common convention, an enzyme's name consists of a description of what it does, with the word ending "-ase" added; examples are alcohol dehydrogenase and DNA polymerase.

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