Monday, October 22, 2012

Enzyme Inhibition

Type of InhibitionEffect on Maximum Reaction Velocity(Vmax)Effect on Km(Affinity of Enzyme for its substrate)Reversible/ IrreversibleExamples
Competitive Inhibition 
(Inhibitor- a structural Analogue).

There is a competition between  substrate and the inhibitor for the active site
UnchangedIncreasedReversible1) HMG Co A Reductase- inhibited by Statins- used as cholesterol lowering drugs. 
2) Epoxide Reductase – inhibited by Dicoumarol- used as an anticoagulant.

3) Dihydrofolate Reductase-inhibited by Methotrexate- used as anticancer drug.

4) Pteroyl Synthase- inhibited by PABA (Para- amino –benzoic –acid) used as antibiotic.

5) Angiotensin convertase enzyme Inhibitor- inhibited by Captopril –used as an antihypertensive drug.

6) Succinate dehydrogenase- inhibited by Malonate acts as a poison.

7) Lactate dehydrogenase- inhibited by Oxamate- acts as a poison.

Non competitive(Inhibitor binds at a site other than the active site)DecreasedUnchangedCan be reversible or irreversible1) Enolase is inhibited by Fluoride used for sample collection for glucose estimation. 
2) PDH complex, Alpha ketoglutarate dehydrogenase complex, glyceraldehyde-3-P dehydrogenase(-SH group containing enzymes) are inhibited by Arsenate, Acts as a slow poison

3) Cytochrome oxidase- Inhibited by cyanide acts as a poison.

4)Cyclooxygenase is inhibited by Aspirin-used as an anti inflammatory, analgesic and antipyretic  drug (Inhibits formation of prostaglandins)

Suicidal inhibition,  
Also calledMechanism based  inhibition

 Inhibitor gets activated by host enzyme to inhibit the subsequent enzyme
DecreasedIncreasedIrreversible1)Inhibition of Xanthine oxidase by Allopurinol, used for the treatment of gout. 
2) Inhibition of Aconitase by fluoroacetate- used as a rat poison

3) Inhibition of Transpeptidase by Penicillin- used as an antibiotic

4) Inhibition of Ornithine decarboxylase by Di fluoro methyl ornithine(DFMO)

5) Mono Amine Oxidase is inhibited by Deprenyl used to treat Parkinson disease and depression.
Allosteric Inhibition (Binding of the inhibitor alters either the affinity of the enzyme for its substrate or the reaction velocity is decreasedV max is decreased in V type enzymesKm is increased in K type enzymesReversibleMost of them are physiological inhibitors.  
1)ATP and Citrate are allosteric inhibitors of PFK-1

2) Fr 2,6 bisphosphate is an allosteric inhibitor of Fr1,6 bisphosphatase enzyme.

Feed back inhibition, also called Product inhibition The product of the reaction pathway inhibits the key  regulatory enzyme.DecreasedconstantReversible depending upon the need of the product1) Inhibition of HMG Co A Reductase by Mevalonate(Immediate product) and cholesterol(Final product) 
2) Inhibition of Aspartate transcarbamoylase
by UTP and CTP, the products of this pathway.
Un competitive inhibition Inhibitor binds to the enzyme substrate complexDecreasedDecreasedIr- reversibleInhibition of  placental alkaline phosphatase by Phenyl Alanine

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