Enzymes

Enzymes

• Are biological catalysts • Catalysts are substances that that increase the

speed of a chemical reaction by lowering the energy requirement

• Although a catalyst influences a chemical reaction, it is not itself permanently changed, nor does it cause the reaction to occur.

• A catalyst can increase the rate of a chemical reaction but cannot cause the reaction .

Enzymes

• Catalysts are not used up so they can be used over and over again.

• Enzymes are organic catalysts produced by the body

• The reactant in an enzyme catalyzed reaction is called the substrate

• The active site of an enzyme is the small portion of the molecule that is responsible for the catalytic action of the enzyme.

• Enzyme provide a chemical pathway that has a lower activation energy than that without the enzyme.

Enzymes.

• Enzymes are highly specific with varying degrees of specificity.

• Some enzymes exhibit absolute specificity• That is they act on substrate and only on that

substrate.• Some enzymes also exhibit stereo specificity.

Such enzymes can detect difference between optical isomers.. mirror images and select only one of such isomers.

• Some enzymes are linkage specific i.e they catalyze the reaction that breaks the bond only between specific groups.

Enzymes

• For example the enzyme thrombin will break the bonds between amino acids arginine and glycine and does not affect bonds between other amino acids.

• Other enzymes exhibit reaction specificity i.e. they catalyze certain types of reaction

• E.g. Carbohydrases catalyzes the hydrolysis of carbohydrates.

• Other enzymes exhibit group specificity e.g. chymotrypsin catalyzes the hydrolysis of only those proteins that contain phenylalanine, tryptophan or tyrosine

Regulation

• The activities of enzymes is closely regulated .• There are substances in the cells that can

increase or decrease the activity of the enzyme and thus control the rate of that particular reaction.

• Enzymes are proteins and so undergo the same reactions.

• They are coagulated by heat, alcohol, strong acids.

Regulation

• Temperature

• PH

• Effects of concentration.

OPTIMUM PH

Optimum Temperature

Activators and inhibitors

• Inorganic substances that tend to increase the activity of an enzyme are called activators.

• For example, the magnesium ion (Mg2+) is an inorganic activator for the enzyme phosphatase, and zinc ion (Zn2+) is an activator for the enzyme carbonic anhydrase.

• An enzyme inhibitor is any substance that will make an enzyme less active or render it inactive.

• Enzyme inhibitors that bind reversibly to the active site and so block access by the substrate are called competitive inhibitors.

Activators and inhibitors

• Their effect can be overcome by increasing the concentration of the substrate.

• Other inhibitors that bind to another site on the enzyme to render it less active or inactive are called non competitive inhibitors.

• They act by changing the conformation of the enzyme, thereby reducing or stopping its activity.

• Irreversible inhibitors form strong covalent bonds with the enzymes rendering it inactive.

• This effect cannot be overcome by increasing the concentration of the substate.

• Zalcitabin ( DIDEOXYCYTIDINE ) is used in patients with advanced HIV infection.

• Inside the cell, Zalcitabin is converted into its active metabolite dideoxycytidine 5’-triphosphate (ddCTP).

• This in turn act as a competitive inhibitor of the natural substrate deoxycytidine triphosphate (dCTP) for the active site of the viral reverse transcriptase ..

• As a result of this competitive inhibition, the replication of the HIV 1 is inhibited.

Activators and inhibitors

• Heat changes in PH, heat, strong acids, alcohols can all denature protein.

• These are examples of nonspecific inhibitors.• They affect all enzymes in the same manner.• Specific inhibitors affect one single enzyme or

group of enzymes• In this category are most poisonous substances,

such as cyanide ion (CN) which inhibits the activity of the enzyme cytochrome oxidase.

Poisons

• Many enzyme inhibitors are poisonous because of their effect on enzyme activity.

• Mercury and lead compounds are poisonous because they react with the sulfhydryl group (-SH) of an enzyme and so change its conformation.

• The subsequent loss of enzyme activity leads to the various symptoms of lead and mercury poisoning such as loss of equilibrium, hearing, sight and touch which are generally irreversible.

Poisons

• While some enzyme inhibitors are poisonous, others are beneficial to life.

• Penicillins act as an enzyme inhibitor for transpeptidase, a substance that bacteria need to build their cell walls.

• If the cell wall is lacking, osmotic pressure causes the bacteria cell to burst and die.

• Cyclic AMP acts a chemical messanger to regulate enzyme activity within the cells that store carbohydrates and fat.

• Without cAMP, the activity of all enzymes working at maximum speed within the cell would soon create chaos.

Mode of Activity

• Each enzyme contains an active site.• Active site is that section of the molecule

at which combination of the substrate takes place.

• The active site consists of different parts of the protein chain (the enzyme)

• These parts are brought together by the folding and bending of the protein chain (the secondary and tertiary structures)

Mode of Activity

• So that the active site occupies a relatively small area.

• The fact that enzymes can be denatured by heat indicates the importance of structural arrangement.

• It is believed that enzyme activity occurs in 2 steps.

• First the active site of the enzyme combines with the substrate to form an enzyme – substrate complex

Lock and key

• The Enzyme – substrate complex then breaks up to form the product and the free enzyme which can react again

• This theory is known as the LOCK AND KEY THEORY.

• According to this theory, the substrate must ‘’FIT” into the active site of the enzyme.

• This accounts for the Specificity of the enzyme.

Lock and Key

Induced – Fit model

• A more recent version of the activity of an enzyme ..the induced fit model suggests that the active site is not rigid , as in the lock and key model but flexible.

• That is the site changes in conformation upon binding to a substrate in order to yield an enzyme-substrate fit.

Induced Fit model