JNTU Pharm. D I Year MEDICIAL BIOCHEMISTRY Previous Question Paper (February/March - 2023 - R08)

Enzyme inhibitors are substances that bind to enzymes and decrease their catalytic activity. They can be classified based on the nature of their binding as reversible or irreversible.

Reversible inhibitors bind to enzymes through non-covalent interactions, such as hydrogen bonds, hydrophobic interactions, or ionic bonds, allowing the inhibitor to dissociate from the enzyme.

• Competitive inhibition: The inhibitor resembles the substrate and competes for the active site. This can be overcome by increasing substrate concentration. Example: Malonate competes with succinate for the enzyme succinate dehydrogenase.
• Non-competitive inhibition: The inhibitor binds to a site other than the active site (allosteric site), changing the enzyme's conformation regardless of substrate concentration. Example: Heavy metal ions like lead or mercury binding to sulfhydryl groups.
• Uncompetitive inhibition: The inhibitor binds only to the enzyme-substrate complex. This decreases both Vmax and Km. Example: Glyphosate inhibiting the enzyme EPSP synthase in plants.

Hypercholesterolemia is a condition characterized by elevated levels of cholesterol in the blood, specifically an increase in low-density lipoprotein (LDL) cholesterol. It is a major risk factor for the development of atherosclerosis and cardiovascular diseases.

The condition arises from either genetic factors, such as familial hypercholesterolemia (a mutation in the LDL receptor gene leading to impaired clearance of LDL from the blood), or secondary factors like high-fat diets, obesity, sedentary lifestyle, diabetes, or hypothyroidism. Excess cholesterol accumulates in the arterial walls, forming plaques that restrict blood flow.

Management involves lifestyle modifications, including a low-saturated fat diet, regular exercise, and weight management. Pharmacological interventions primarily focus on HMG-CoA reductase inhibitors (statins), which block the rate-limiting step of endogenous cholesterol synthesis in the liver, thereby upregulating LDL receptors and lowering serum cholesterol levels. Other treatments may include bile acid sequestrants or cholesterol absorption inhibitors.