ENZYME INHIBITION TEACHER: SIDDHARTH V. PATIL SCHOOL : PODAR INTERNATIONAL SCHOOL SUBJECT: BIOLOGY (HL)

induced fit model

Competitive inhibitors This 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 a similar shape to the usual substrate for the enzyme, and competes with it for the active site The activity of the enzyme is inhibited till the inhibitor has a 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. out-compete That means that if you increase the concentration of the substrate, the substrate can out-compete the inhibitor, and so the normal reaction can take place at a reasonable rate Succinate Fumarate Malonate structure similar to succinate

sulfanilamide para-aminobenzoic acid (PABA) folic acid EXAMPLE 2 : The antibiotic sulfanilamide is similar in structure to para-aminobenzoic acid (PABA), an intermediate in the biosynthetic pathway for folic 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 PABA Folic acid Sulphanilamide (inhibitor) NO Folic acid formation after inhibition

Methanol Formic acid ethanol (inhibitor) Formaldehyde Cause damage to the optic nerve oxidized Ethylene glycol Products formed ethanol (inhibitor) Cause irreversible damage to the kidneys Example 4 Example 3 REVERSIBLE 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 cannot prevent the binding of the inhibitor Substrates cannot prevent the binding of the inhibitor Enzyme molecule stays inhibited. MORPHINE binds to a site other than the active site of the enzyme Nitric oxide synthase. Arginine Nitric oxide Citrulline Nitric oxide synthase Opioids ( morphine) inhibit NOS

Example 2 CN - Cyanide attaches to the –SH group of an enzyme CYTOCHROME C OXIDASE. OXYGEN WATER Cytochrome c oxidase CN - Cyanide 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 product inhibition

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- Have non overlapping binding sites 1)Active site – for substrate 2)Allosteric site- binding site for end product When end product is bound to allosteric site, enzyme is altered Hence substrate is less likely to bind to active site

ADVANTAGE WHOLE PATHWAY IS SWITCHED OFF when end product is saturated and intermediates don’t build up (-ve feed back) When end product levels fall, enzyme 1 gets free from the end product and the whole pathway is re- activated