ENZYME INHIBITION

TEACHER: SIDDHARTH V. PATILSCHOOL : PODAR INTERNATIONAL

SCHOOL SUBJECT: BIOLOGY (HL)

induced fit model

Competitive inhibitorsThis is the most straightforward and obvious form of enzyme inhibition - and the name tells you exactly what happens.

However, once it is attached to the active site, nothing happens to it. It doesn't react - essentially, it just gets in the way.

the general equation for an enzyme reacting with a substrate

The equivalent equation for a competitive inhibitor looks like this:

The inhibitor has The inhibitor has a similar shape a similar shape to the usual to the usual substrate for the substrate for the enzyme, and enzyme, and competes with it competes with it for the active sitefor the active site

The activity of The activity of the enzyme is the enzyme is inhibited till the inhibited till the inhibitor has a inhibitor has a dissociated.dissociated.

The complex doesn't react any further to form products - but its formation is still reversible. It breaks up again to form the enzyme and the inhibitor molecule.

That means that if you increase the concentration of the substrate, the substrate can out-compete out-compete the inhibitor, and so the

normal reaction can take place at a reasonable rate

Succinate

Fumarate

Malonate structure similar to succinate

EXAMPLE 2 : The antibiotic sulfanilamide sulfanilamide is similar in structure to para-aminobenzoic acid (PABA)para-aminobenzoic acid (PABA), an intermediate in

the biosynthetic pathway for folic acidfolic acid. Sulfanilamide can competitively inhibit the enzyme that has PABA as it's normal

substrate by competitively occupying the active site of the enzyme. IRREVERSIBLE COMPETITIVE INHIBITION

PABAPABA Folic acidFolic acid

Sulphanilamide (inhibitor)Sulphanilamide (inhibitor) NO Folic acid formation after inhibitionNO Folic acid formation after inhibition

Methanol Methanol

Formic Formic acidacid

ethanol (inhibitor)ethanol (inhibitor)

FormaldehydeFormaldehyde

Cause damage to the optic nerveCause damage to the optic nerve

oxidizedoxidized

Ethylene glycol Ethylene glycol Products formed Products formed

ethanol ethanol (inhibitor)(inhibitor)

Cause irreversible damage to the Cause irreversible damage to the kidneyskidneys

Cause irreversible damage to the Cause irreversible damage to the kidneyskidneys

Example 4Example 4

Example 3Example 3REVERSIBLE COMPETITIVE INHIBITION

Non-competitive inhibition

• Substrates and inhibitors do not have a similar structure.

• Inhibitors bind at a different site from the active site

• Inhibitors hence change the conformation of the enzyme.

• Substrate may/may not bind • Active site doesn’t catalyze the reaction

Non-competitive inhibition

• Substrates cannot prevent the binding of the cannot prevent the binding of the inhibitorinhibitor

• Enzyme molecule stays inhibited.• MORPHINE binds to a site other than the

active site of the enzyme Nitric oxide synthase.

Arginine Arginine Nitric Nitric oxideoxide

CitrullineCitrullineNitric oxide synthaseNitric oxide synthase

Opioids ( morphine) in

hibit NOS

Example 2

• CN- Cyanide attaches to the –SH group of an enzyme CYTOCHROME C OXIDASE.

OXYGEN OXYGEN

WATERWATER

Cytochrome c oxidaseCytochrome c oxidase

CNCN- - Cya

nide

Cyanid

e • S-S bonds are broken and the tertiary structure

of the enzyme is affected and enzyme doesn’t function resulting in the stopping of cellular respiration.

End End product product

inhibitioninhibition

End product inhibition is negative feedback used to regulate the production of a given molecule.

The initial substrate is a molecule that is altered in three steps by enzymes 1,2 and 3. The end product will combine with enzyme 1 to stop the reaction so there will not be an excess production of the end product..

End-product inhibition

•Metabolic reactions are multi-stepped, each controlled by a single enzyme

•End-products accumulate within the cell and stop the reaction when sufficient product is made

•This is achieved by non-competitive inhibition by the end-product

•The enzyme early in the reaction pathway is inhibited by the end-product

ALLOSTERIC ENZYMES- ALLOSTERIC ENZYMES- Have non overlapping binding sites1)Active site – for substrate 2)Allosteric site- binding site for end product

When end product is bound to allosteric site , enzyme is alteredHence substrate is less likely to bind to active site

ADVANTAGEADVANTAGE

WHOLE PATHWAY IS SWITCHED OFF WHOLE PATHWAY IS SWITCHED OFF when when end product is saturated end product is saturated and and intermediates don’t build up intermediates don’t build up (-ve feed (-ve feed back)back)

When When end product levels fall, end product levels fall, enzyme 1 enzyme 1 gets free from the end product gets free from the end product and the and the whole pathway is re- activated whole pathway is re- activated