Part Five: Regulatory Enzymes

• Regulatory enzymes are involved in catalytic activity increases and decreases in response to certain signals. This allows the cell to meet changing needs for energy and biomolecules.
• The activities of regulatory enzymes are modulated by allosteric enzymes, reversible covalent bonding, the binding of regulatory proteins, and the removal of peptide segments by proteolytic cleavage.
• Allosteric enzymes function through reversible binding of regulatory compounds called allosteric modulators or allosteric effectors (small metabolites or cofactors).
• Allosteric enzymes undergo conformational changes in response to modulator binding.
• Homotrophic allosteric enzymes are enzyme regulation in which the substrate and modulator are identical.
• Heterotropic allosteric enzymes are enzyme regulation in which the modulator is a molecule other than the substrate.
• Aspartate transcarbamoylase (ATCase) catalyzes the formation of carbamoyl aspartate, an early step in pyrimidine biosynthesis.
• When allosteric enzymes are plotted, the plots of V_0 verses [S] usually produces a sigmoid separation curve, rather than a hyperbolic core.
• For allosteric enzymes, [S]_0.5 or K_0.5 represents [S] giving half maximal velocity of the reaction.
• With homotropic enzymes, there is a relatively small increase in [S] in the steep part of the curve causes a comparatively large increase in V_0.
• For heterotropic allosteric enzymes, activators may cause the curve to become more hyperbolic and an inhibitor may cause the curve to become more sigmoidal.
• Modulation in which V_max, but not K_0.5, is altered is a less common type of modulation for heterotropc allosteric enzymes.
• Some enzymes are regulated by reversible covalent modification. This can include phosphorylation (Tyr, Ser, Thr, His), adenylylation (Tyr), acetylation (Lys, amino terminus), myristoylation (amino terminal), ubiquitination (Lys), ADP ribosylation (Arg, Gln, Cys, diphthamide), and methylation (Glu).
• Phosphoryl groups affect the structure and catalytic activity of enzymes.
• Protein kinases catalyze the attachment of phosphoryl groups to specific amino acid residues (Ser, Thr, Tyr, and His).
• Phosphoprotein phosphatases, or protein phosphatases, remove phosphoryl groups from the same target proteins.
• Residues that are typically phosphorylated in regulated proteins occur within common structural motifs, consensus sequences.
• Multiple regulatory phosphorylations provide the potential for extremely subtle modulation of enzyme activity.
• Sequential phsophorylation processes can be hierarchical.
• Some enzymes and other proteins are regulated by proteolytic cleavage of an enzyme precursor.
• Zymogen is an inactive precursor that is cleaved to form an active protease enzyme.
• Proprotein or proenzyme are precursors that are cleaved to form other proteins.
• A cascade of proteolytically activated zymogens leads to blood coagulation.
• A regulator cascade is a mechanism that allows a very sensitive response to, and amplification of, a molecular signal. An example of the formation of a blood clot.
• A blood clot is an aggregate of specialized cell fragments that lack nuclei (platelets) cross linked and stabilized by proteinaceous fibers consisting mainly of the protein fibrin, derived from the soluble zymogen fibrinogen.
• Platelet activation is caused by collagen exposure to air. This causes the release of signaling molecules, such as thromboxanes to stimulate the activation of additional platelets.
• Fibrinogen is converted to fibrin by the proteolytic removal of amino acid residues.
• Thrombin is a serine protease that catalyzes peptide removal.
• Factor XIIIa is a transglutaminase enzyme that catalyzes the formation of covalent cross links between fibrins.
• Two regulatory cascades lead to fibrinogen activation

  • The intrinsic pathway involves all components found in the blood plasma
  • The extrinsic pathway, or tissue factor pathway, involves the protein tissue factor, TF, which is not present in blood.
• Some regulatory enzymes use several regulatory mechanisms.
• When chemical resources are plentiful, cells synthesize and store glucose and other matabolites.
• When chemical resources are scarce, cells use these stores to fuel cellular metabolism.
• The availability of specific catalysts allows for the regulation of these reactions.