JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D I Year MEDICIAL BIOCHEMISTRY Previous Question Paper (January/February - 2021 - R08)

Transport across the cell membrane is classified into passive transport, which occurs along the concentration gradient without energy expenditure, and active transport, which requires energy to move substances against a gradient. Passive processes include simple diffusion, facilitated diffusion, and osmosis. Active transport mechanisms include primary active transport, which directly utilizes ATP, and secondary active transport, which uses the electrochemical gradient established by primary transport.

The active transport mechanism involves specialized membrane proteins known as pumps or carriers. In primary active transport, these proteins possess ATPase activity, allowing them to hydrolyze ATP to ADP and inorganic phosphate, providing the energy necessary to induce a conformational change in the protein. This change moves specific ions or molecules (such as the Na+/K+-ATPase pump) against their electrochemical gradient. By maintaining these gradients, cells regulate osmotic balance, pH, and membrane potential, which are essential for cellular homeostasis.

Irreversible competitive inhibition occurs when an inhibitor binds so tightly to the active site of an enzyme, typically through the formation of a covalent bond, that it cannot be dissociated. Unlike reversible competitive inhibition, where the inhibitor and substrate compete for the active site and can be displaced by increasing substrate concentration, an irreversible inhibitor permanently inactivates the enzyme molecule. Consequently, the maximum velocity (Vmax) of the reaction decreases as the effective concentration of functional enzyme is reduced, and the inhibition cannot be overcome by adding more substrate.

A classic example is the action of aspirin (acetylsalicylic acid), which irreversibly inhibits the enzyme cyclooxygenase (COX). Aspirin acetylates a specific serine residue within the active site of the enzyme, permanently blocking the binding of its natural substrate, arachidonic acid, thereby preventing the synthesis of prostaglandins and thromboxanes.