Zymogen activation by partial proteolysis is an example of -
Ans. D. Covalent modificationRegulation of Enzyme Activity: -A. Allosteric binding sites: -1. Allosteric enzymes are regulated by molecules called effectors (also called modifiers) that bind noncovalently at a site other than the active site. These enzymes are usually composed of multiple subunits, and the regulatory site that binds the effector may be located on a subunit that is not itself catalytic.2. The presence of an allosteric effector can alter the affinity of the enzyme for its substrate, or modify the maximal catalytic activity of the enzyme, or both. Effectors that inhibit enzyme activity are termed negative effectors, whereas those that increase enzyme activity are called positive effectors. Allosteric enzymes frequently catalyze the committed step early in a pathway.3. Homotropic effectors: When the substrate itself serves as an effector, the effect is said to be homotropic. Most often, an allosteric substrate functions as a positive effector. In such a case, the presence of a substrate molecule at one site on the enzyme enhances the catalytic properties of the other substrate-binding sites--that is, their binding sites exhibit cooperativity.4. These enzymes show a sigmoidal curve when reaction velocity (vo) is plotted against substrate concentration (). This contrasts with the hyperbolic curve characteristic of enzymes following Michaelis-Menten kinetics, as previously discussed. Positive and negative effectors of allosteric enzymes can affect either the Vmax or the Km, or both.5. Heterotropic effectors: The effector may be different from the substrate, in which case the effect is said to be heterotropic. The enzyme that converts D to E has an allosteric site that binds the end product, G. If the concentration of G increases (for example, because it is not used as rapidly as it is synthesized), the first irreversible step unique to the pathway is typically inhibited.6. Feedback inhibition provides the cell with a product it needs by regulating the flow of substrate molecules through the pathway that synthesizes that product. Heterotropic effectors are commonly encountered, for example, the glycolytic enzyme phosphofructokinase-1 is allosterically inhibited by citrate, which is not a substrate for the enzyme.B. Regulation of enzymes by covalent modification: -1. Many enzymes may be regulated by covalent modification, most frequently by the addition or removal of phosphate groups from specific serine, threonine, or tyrosine residues of the enzyme. Protein phosphorylation is recognized as one of the primary ways in which cellular processes are regulated.2. Phosphorylation and dephosphorylation: Phosphorylation reactions are catalyzed by a family of enzymes called protein kinases that use adenosine triphosphate (ATP) as a phosphate donor. Phosphate groups are cleaved from phosphorylated enzymes by the action of phosphoprotein phosphatases.3. For some enzymes, an inactive precursor called a zymogen is cleaved to form the active enzyme. Many proteolytic enzymes (proteases) of the stomach and pancreas are regulated in this way. Chymotrypsin and trypsin are initially synthesized as chymotrypsinogen and trypsinogen. Specific cleavage causes conformational changes that expose the enzyme active site.C. Induction and repression of enzyme synthesis: -1. The regulatory mechanisms described above modify the activity of existing enzyme molecules. However, cells can also regulate the amount of enzyme present--usually by altering the rate of enzyme synthesis. The increase (induction) or decrease (repression) of enzyme synthesis leads to an alteration in the total population of active sites. Enzymes subject to regulation of synthesis are often those that are needed at only one stage of development or under selected physiologic conditions.2. For example, elevated levels of insulin as a result of high blood glucose levels cause an increase in the synthesis of key enzymes involved in glucose metabolism. In contrast, enzymes that are in constant use are usually not regulated by altering the rate of enzyme synthesis.3. Alterations in enzyme levels as a result of induction or repression of protein synthesis are slow (hours to days), compared with allosterically regulated changes in enzyme activity, which occur in seconds to minutes.
Allosteric modification
Enzyme induction
Enzyme repression
Covalent modification
Enzyme Kinetics