Enzyme

In biology, an enzyme (from Greek: "in ferment") is a protein, or assemblage of protein molecules, which facilitates (and/or accelerates) a biochemical reaction; enzymes are a form of catalyst. Many chemical reactions occur within cellss; but, without enzymes, most of them would happen too slowly to sustain life.

Table of contents
1 Role of enzymes in chemical reactions
2 Enzymes and health
3 Digestive and metabolic enzymes
4 Enzyme naming conventions
5 Enzymes and classes of enzyme
6 External links

Role of enzymes in chemical reactions

Enzymes can also serve to couple two or more reactions together, so that a thermodynamically favourable reaction can be used to "drive" a thermodynamically unfavorable one. One of the most common examples is enzymes which use the dephosphorylation of ATP to drive some otherwise unrelated chemical reaction.

Chemical reactions need a certain amount of activation energy to take place. Enzymes can increase the reaction speed by favoring or enabling 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 usually specific as to the reactions they catalyze and the chemicals (substrates) that are involved in the reactions. Complementary structural properties of the enzyme and substrate are responsible for this specificity (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.


Figure 1: Diagram of a catalytic reaction, showing the energy needed (E) against time (t). The substrates (A and B) need a large amount of energy (E1) to reach the transition state A...B, which then reacts to form the end product (AB). The enzyme (E) creates a microenvironment in which A and B can reach the transition 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.


Figure 2: An enzyme (E) catalyzes the reaction of two substrates (S1 and S2) to form one product (P). Enzymes can perform up to several million catalytic reactions per second. To determine the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is achieved (Fig. 3). This is the maximum velocity (Vmax) of the enzyme. In this state, all enzyme active sites 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 at which the rate of reaction is half its maximum. This substrate concentration is called the Michaelis-Menten constant (KM). Many enzymes obey Michaelis-Menten kinetics.


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.

Several factors can influence the reaction speed, catalytic activity, and specificity of an enzyme. Besides de novo synthesis (the production of more enzyme molecules to increase catalysis rates), properties such as pH or temperature can denature 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 cofactors like metal ions or organic molecules (e.g., NAD+, FAD, CoA, or certain vitamins) that interact with the enzyme. Allosteric enzymes are composed either of effector binding sites or mulitple protein subunits that interact with each other and thus influence catalytic activity. Enzymes can also 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.


Figure 4: Competitive inhibition.
A competitive inhibitor (I) fits the enzyme (E) as well 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 binding with a substrate (S) molecule. Some inhibitors (I) form covalent bonds with the enzyme (E), inactivating it permanently (suicide inhibitors).


Figure 5: Uncompetitive inhibition.
Uncompetitive inhibitors/activators (I) do not bind to the active center, but to 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).


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 committed 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 and health

Enzymes are essential to living organisms, and a malfunction of even a single enzyme out of approximately 2,000 present in our bodies can lead to severe or lethal illness. An example of a disease caused by an enzyme malfunction in humans is phenylketonuria (PKU). The enzyme phenylalanine hydroxylase, which usually converts 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 good or bad ways. Aspirin, for example, inhibits an enzyme that produces prostaglandins (inflammation messengers), thus suppressing pain. But not all enzymes are in living things. Enzymes are also used in everyday products such as washing detergents, where they speed up chemical reactions involved in cleaning the clothes (for example, breaking down blood stains).

Digestive and metabolic enzymes

Nutrition in animals relies on digestive enzymes such as salivary amylase, trypsin and chymotrypin. Their primary role is for the digestion of food and making nutrients available to all of the body processes which need them. Another class of enzymes is called metabolic enzymes. Their role is to catalyze chemical reactions involving every process in the body, including the absorption of oxygen. Most of our cells (an exception being erythrocytes), would literally starve for oxygen even with an abundance of oxygen without the action of the enzyme, cytochrome oxidase. Enzymes are also necessary for muscle contraction and relaxation. The fact is, without both of these classes of enzymes, (digestive and metabolic) life could not exist.

Enzyme naming conventions

By common convention, an enzyme's name consists of a description of what it does, with the word ending in "-ase". Examples are alcohol dehydrogenase and DNA polymerase. Kinases are enzymes that transfer phosphate groups. The International Union of Biochemistry and Molecular Biology has developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers, preceded by "EC". The first number broadly classifies the enzyme based on its mechanism:

  • EC 1 Oxidoreductases: catalyze oxidation/reduction reactions
  • EC 2 Transferases: transfer a functional group (e.g., a methyl or phosphate group)
  • EC 3 Hydrolases: catalyze the hydrolysis of various bonds
  • EC 4 Lyases: cleave various bonds by means other than hydrolysis and oxidation
  • EC 5 Isomerases: catalyze isomerization changes within a single molecule
  • EC 6 Ligases: join two molecules with covalent bonds

The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/

Enzymes and classes of enzyme

External links

  • ExPASy enzyme database, links to Swiss-Prot sequence data, entries in other databases and to related literature searches
  • PDBsum links to the known 3-D structure data of enzymes in the Protein Data Bank
  • BRENDA, comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users



copyright 2004 FactsAbout.com