enzyme inhibitors

Comprehensive vocabulary flashcards covering the classification, clinical examples, kinetics, and regulation of enzyme inhibitors based on Lecture 9.

Reversible Inhibitors

Inhibitors characterized by non-covalent binding that can dissociate from the enzyme.

Irreversible Inhibitors

Inhibitors that involve covalent binding to the enzyme, leading to permanent inactivation.

Competitive Inhibition

A type of inhibition where the inhibitor binds to the active site and competes with the substrate; it increases $K_m$ but leaves $V_{max}$ unchanged.

Non-Competitive Inhibition

Inhibition where the inhibitor binds to an allosteric site on the enzyme or enzyme-substrate complex, decreasing $V_{max}$ while $K_m$ remains unchanged.

Un-Competitive Inhibition

A rare type of inhibition where the inhibitor binds only to the enzyme-substrate ($ES$) complex, lowering both $V_{max}$ and $K_m$; an example is the use of $Li^+$ for manic depression.

Suicide Inhibitor

A substrate analog that covalently inactivates the enzyme after being converted into a reactive intermediate during catalysis.

Sulfonamides

Clinical drugs that act as competitive inhibitors of Folate Synthase.

Trimethoprim and Methotrexate

Antibiotics and chemotherapy agents that act as competitive inhibitors of Dihydrofolate Reductase ($DHFR$).

Fomepizole

A competitive inhibitor of alcohol dehydrogenase ($ADH$) used to treat methanol and ethylene glycol poisoning by preventing the production of toxic metabolites.

Statins (Lovastatin, Simvastatin)

Hypocholesterolemic drugs that are structural analogues of $HMG-CoA$ and competitively inhibit $HMG-CoA$ reductase, the rate-limiting enzyme of cholesterol synthesis.

Lead ($Pb^{2+}$) Inhibition

A non-competitive inhibitor of heme synthesis that binds to sulfhydryl ($-SH$) groups of cysteine residues on enzymes, causing conformational changes.

Organophosphorus Poisoning

Irreversible inhibition of acetylcholinesterase in the neuromuscular junction by nerve gases (Sarin, Tabun) or insecticides (malathion), leading to acetylcholine accumulation.

Disulfiram

An irreversible inhibitor of Acetaldehyde dehydrogenase ($AlDH$) used therapeutically to treat alcohol abuse by causing the accumulation of acetaldehyde.

Aspirin

A suicide inhibitor that acetylates the serine residue in the active site of the $COX$ enzyme, permanently inhibiting prostaglandin synthesis.

Allopurinol

A suicide inhibitor used to treat gout by permanently binding to the active site of xanthine oxidase to reduce uric acid formation.

5-Fluorouracil (5-FU)

A suicide inhibitor used in chemotherapy that forms a covalent complex with thymidylate synthase and folate to block DNA synthesis.

Allosteric Effectors

Molecules that bind noncovalently to an allosteric site to cause conformational changes (cooperativity) that alter enzyme affinity ($K_m$) or maximal activity ($V_{max}$).

R state vs. T state

In allosteric regulation, the $R$ state represents high enzymatic activity, while the $T$ state represents low activity; activators push the enzyme toward the $R$ state.

Kinases

Enzymes that catalyze the reversible phosphorylation of proteins at serine, threonine, and tyrosine residues.

Phosphatases

Enzymes that catalyze the dephosphorylation of proteins to regulate enzymatic activity.

Zymogens (Proenzymes)

Inactive precursors to enzymes that must be proteolytically cleaved to become active, such as factors in the complement and coagulation cascades.

Enzyme Compartmentation

The physical separation of enzymes and substrates into distinct cellular areas, such as lysosomal acid hydrolases being kept at $pH$ $4.5-5.0$ separate from the cytoplasm.