Enzyme

An enzyme (from Greek énsimo (??????), formed by én = at or in and simo = leaven or yeast) is a protein that catalyzes, or speeds up, a chemical reaction.

3D-Structure

In enzymes, as with other proteins, function is determined by structure. An enzyme can be:

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

• A monomeric protein, i.e., containing only one polypeptide chain, made up of about hundred amino acids or more; or
• an oligomeric protein consisting of several polypeptide chains, different or identical, that act together as a unit.

As with any protein, each monomer is actually produced as a long, linear chain of amino acids, which folds in a particular fashion to produce a three-dimensional product. Individual monomers may then combine via non-covalent interactions to form a multimeric protein.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Most enzymes are far larger molecules than the substrates they act on and that only a very small portion of the enzyme, around 10 amino acids, come into direct contact with the substrate(s). This region, where binding of the substrate(s) and than the reaction occurs, is known as the active site of the enzyme. Sometimes enzymes contain additionally other binding sites. Some enzymes have a binding site for a cofactor, which is needed for catalysis. Some enzymes have a binding site that serve regulatory functions, which increase or decrease the enzyme's activity. These typically bind small molecules, often direct or indirect products or substrates of the reaction catalyzed. This provides a means for feedback regulation.

Related Topics:
Active site - Regulatory - Indirect - Feedback

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

The amino acid sidechains of an enzyme are either involved in forming the active site or a binding site, or are needed to form the 3D-structure of the protein. Some amino acid sidechains are not needed for function or structure of the enzyme.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Specificity

Enzymes are usually specific as to the reactions they catalyze and the substrates that are involved in these reactions. Shape and charge complementarity of enzyme and substrate are responsible for this specificity.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

"Lock and key" hypothesis

Enzymes are very specific and it was suggested by Emil Fischer in 1890 that this was because the enzyme had a particular shape into which the substrate(s) fit exactly. This is often referred to as "the lock and key" hypothesis.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

An enzyme combines with its substrate(s) to form a short lived enzyme-substrate complex.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Induced fit hypothesis

In 1958 Daniel Koshland suggested a modification to the "lock and key" hypothesis. Enzymes are rather flexible structures. The active site of an enzyme could be modified as the substrate interacts with the enzyme. The amino acids sidechains which make up the active site are molded into a precise shape which enables the enzyme to perform its catalytic function. In some cases the substrate molecule changes shape slightly as it enters the active site.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

A suitable analogy would be that of a hand changing the shape of a glove as the glove is put on.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Modifications

Many enzymes contain not only a protein part but need additionally various modifications. These modifications are made posttranslational, i.e. after the polypeptide chain was synthesized. Additional groups can be synthesized onto the polypeptide chain. E.g. phosphorylation or glycolisation of the enzyme.

Related Topics:
Phosphorylation - Glycolisation

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Another kind of posttranslational modification is the cleavage and splicing of the polypeptide chain. E.g. chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This prevents the enzyme from harmful digestion of the pancreas or other tissue. This type of inactive precursor to an enzyme is known as a zymogen.

Related Topics:
Chymotrypsin - Protease - Chymotrypsinogen - Pancreas - Stomach - Zymogen

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Enzyme cofactors

Some enzymes do not need any additional components to exhibit full activities. However, many enzymes are chemically inactive, and they require additional components to become active. An enzyme cofactor is the non-protein component of an enzyme essential for its catalytic activity. There are three types of cofactors, namely activators, coenzymes, prosthetic groups.

Related Topics:
Activator - Coenzyme - Prosthetic group

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Activators

Certain enzymes require inorganic ions as cofactors. These inorganic ions are called activators. They are mainly metallic monovalent or divalent cations which are either loosely or firmly bound to the enzymes. For example in blood clotting, calcium ions, known as factor IV, are required to activate thrombokinase to convert prothrombin into thrombin.

Related Topics:
Inorganic - Ion - Blood clotting - Calcium - Thrombokinase - Prothrombin - Thrombin

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Prosthetic groups

Non-protein organic cofactors which are firmly bound to the enzyme molecules are called prosthetic groups. They combine to form an integral part in performing catalytic functions. FAD, a prosthetic group containing heavy metals, is a prosthetic group having similar function as NAD and NADP in carrying hydrogen. Heme is a prosthetic group responsible for carring electrons in the cytochrome system.

Related Topics:
FAD - Heavy metals - Heme - Cytochrome

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Coenzymes

The cofactors of some other enzymes are non-protein organic molecules known as coenzymes, which are not bonded to enzyme molecules like prosthetic groups. Being vitamin-derivatives, they usually serve as carriers to transfer atoms or functional groups from one enzyme to another. Common examples and NAD (derived from nicotinic acid, a member of vitamin B complex) and NADP, which act as hydrogen carriers in Coenzyme A that transfers the acetyl groups.

Related Topics:
Organic - Coenzyme - Vitamin - Atom - Functional group - NAD - Nicotinic acid - Vitamin B complex - NADP - Hydrogen - Coenzyme A - Acetyl

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Those inactive protein parts of enzymes are called apoenzymes. An apoenzyme works effectively only in the presence of non-protein cofactors. An apoenzyme together with its cofactor constitutes a holoenzyme, i.e., an active enzyme. Most of the cofactors are either regenerated or chemically unchanged at the end of the reactions.

Related Topics:
Apoenzyme - Holoenzyme

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Allosteric modulation

Allosteric enzymes have either effector binding sites, or multiple protein subunits that interact with each other and thus influence catalytic activity.

Related Topics:
Allosteric - Effector - Binding site - Protein subunit

~ ~ ~ ~ ~ ~ ~ ~ ~ ~