Enzymes Derived from Greek World ( En = in, Zyme = Yeast ) Enzymes are commonly proteinaceous substances of high molecular weight which accelerate, or

catalyze, chemical reaction of biological origin without them self undergoing any change. Enzymes have a high degree of specificity for types of reaction catalyzed and for their substrate The term enzymes was coined by Kuhne in 1878 First enzyme extract from yeast cell by Buchner (1897)

Enzyme nomenclature and classificationNomenclature Previously enzymes use to be named by adding ‘in’ e.g. Pepsin, trypsin etc. In 1883 Duclaux proposed the naming of enzymes by adding the suffix "-ase" to the substrate on

which the enzyme acts or the chemical reaction it catalyzes. Example enzymes acting on sucrose as sucrose, enzymes catalyzing oxidation oxidase.

The International Union of Biochemistry and Molecular Biology have developed the EC ( Enzyme commission) numbers of four digits Preceded by “EC”. First digit denotes: Class Second digit denotes: Sub classThird digit denotes: Sub-sub classFourth digit denotes: Sub-sub-sub classFor examples example, hexokinase (EC 2.7.1.1) is a transferase (EC 2) that adds a phosphate group (EC 2.7), a molecule containing an alcohol group (EC 2.7.1) to a hexose sugar (EC 2.7.1.1)

First two digits represents type of reaction it catalyzed, last two digits represents substrate which enzyme acts.

ClassificationThe International Enzyme commission (IEC) system has divided the enzymes into six major groups based on type of reaction catalyzed

EC 1: Oxidoreductases Enzymes of this group add or remove hydrogen and oxygen atoms or electrons from one substance to another during the catalysis

Example: Oxidases, Dehydrogenases, Reductases

EC 2: TransferaseThese enzymes catalyze the transfer of a functional group (methyl-,acyl-,amino- or phosphate) of atoms from one molecule to another.

Examples Transaminase (transfer amino groups), Kinases ( transfer phosphate group )

EC 3 Hydrolases:

Catalyze the hydrolysis  ( cleavage of chemical bonds by the addition of water ) 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 with breakdown of the energy containing

substances.

Properties of enzymes1. Enzyme is specialized protein

It exhibit all properties of proteins2. Colloidal nature : Due to large size of molecules3. Catalytic property

Enzymes are very efficient catalyst. Only small amount of enzymes is enough to convert large quantity of substrate in product. It Speed up reaction by 106 - 1012 times greater than those of the corresponding un catalyzed reactions

4. SpecificEnzymes are more specific toward their substrates and for the type of reactions that catalyze. Enzymes shows 3 types of specificitya. Specific specificity

Some enzymes act on only one substratee.g. Urease acts only on urea.

b. Group specificityCatalyze the reaction of structurally related groups onlyAmylase hydrolyses the group of substances like starch, dextrin and glycogen, which have the same type of glycosidic linkages (α1,4).

c. Optical SpecificityThe enzymes acts on only one of the two optical isomers of a compoundFor example L-amino acid oxidase acts only on L-amino acid but not on its D-form of amino acid.

5. Heat sensitivity ( note )Enzyme is very sensitive to heat. Optimum temperature for enzyme action is 35-37 degree centigrade’s. The enzymes activity decreases below or above this temperature due to denaturation.

6. pH sensitivityEnzyme is dependent upon the pH of where the reaction is taking place, e.g. pepsin in the stomach has an optimum pH of about pH2, Whereas salivary amylase has an optimum pH of about 7. 4.

7. Reversibility of reactionEnzymes are capable of bringing reversion in a chemical reaction

Function of enzymes1) To accelerate or retard or bring about reaction2) Regulate reaction3) To make possible the metabolic reactions4) To facilitate reaction5) To break down larger molecule to small molecule6) To carry out flow of reaction smoothly

Mechanism of enzyme actionEnzymes helps in the progress of the reaction in 2 ways1. Lowering activation energy

2. Formation of enzyme substrate complexThere are three theories to explain formation of enzymes substrate complex.

a. Michaelis-Menton Hypothesis

The theory postulates that the enzymes has number of active sites where the substrate is bounded to form weak enzyme substrate complex (S). This enyzme-substrate complex, on hydrolysis, decomposes to yield the reaction product (P) and the free enzyme (E). These reactions may be symbolically represented as follows:

[S] + [E] ---------->  [ES] ---------> P+[E]

b. Fisher’s lock and key modelThis model was proposed by Emil Fischer in 1898. According to this model, the union between the substrate and the enzyme takes place at the active site more or less in a manner in which a key fits a lock and results in the formation of an enzyme substrate complex. The enzyme-substrate complex is highly unstable and almost immediately this complex decomposes to produce the end products of the reaction and to regenerate the free enzyme.

c. Koshland’s Induced fit model• Enzyme structure flexible, not rigid• Enzyme and active site adjust shape to bind substrate• Increases range of substrate specificity• Shape changes also improve catalysis during reaction

InhibitorsCompounds which convert the enzymes into inactive substances and thus adversely affect the rate of enzymatically-catalyzed reaction are called as enzyme inhibitors. Such a process is known as enzyme inhibition.1. Reversible inhibitors

A reversible inhibitor dissociates very rapidly from its target enzymeA. Competitive inhibitors

• Has a structure similar to substrate• Occupies active site• Competes with substrate for active site• Has effect reversed by increasing substrate concentration

For example:- An enzyme, succinic acid dehydrogenase (= succinodehydrogenase) catalyzes the conversionof succinic acid to fumaric acid.but presence of malonic acid inhibit the reaction.

B. Non-competitive inhibitorsThe inhibitor has little or no structural resemblance with the substrate and it binds with the enzyme at a place other than the active site.

For example presence of heavy metal like Ag+, Hg+2 etc inhibit the activity of a variety of enzymes. Urease.

3. Irreversible inhibitorsIrreversible inhibitors are those that combine with or destroy a functional group on the enzyme that is essential for its activity. For example iodoacetamide irreversibly inhibit the catalytic activity of some enzymes by modifying cysteine.