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Thread: Enzyme Kinetics and Nomenclature Rules

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    PharmD Year 1 TomHsiung's Avatar
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    Default Enzyme Kinetics and Nomenclature Rules

    Enzymes are grouped into the following six classes.
    • Oxidoreductases - enzymes that catalyze oxidations and reductions
    • Transferases - enzymes that catalyze transfer of moieties such as glycosyl, methyl, or phosphoric groups
    • Hydrolases - enzymes that catalyze hydrolytic cleavage of C-C, C-O, C-N, and other covalent bonds.
    • Lyases - enzymes that catalyze cleavage of C-C, C-O, C-N, and other covalent bonds by atom elimination, generating double bonds
    • Isomerases - enzymes that catalyze geometric or structural changes within a molecule
    • Ligases - enzymes that catalyze the joining together (ligation) of two molecules in reactions coupled to the hydrolysis of ATP.
    Last edited by admin; Thu 24th November '16 at 9:20pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    PharmD Year 1 TomHsiung's Avatar
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    Default Lineweaver and Burk plot of Michaelis-Menten equation

    This rearrangement of Michaelis-Menten equation turns a hyperbolic curve plot into a linear plot

    Enzyme Kinetics and Nomenclature Rules-screen-shot-2016-07-31-at-9-11-47-pm-png

    Enzyme Kinetics and Nomenclature Rules-screen-shot-2016-07-31-at-9-13-31-pm-png
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    Default Enzyme inhibitors and how they affect Lineweaver-Burk plot

    Note the intercepts on abscissa and ordinate, respectively.

    Enzyme inhibitors fall into 2 broad classes: those causing irreversible inactivation of enzymes and those whose inhibitory effects can be reversed. Irreversible inhibitors usually cause an inactivating, covalent modification of enzyme structure. The kinetic effect of irreversible inhibitors is to decrease the concentration of active enzyme, thus decreasing the maximum possible concentration of ES complex. Reversible inhibitors can be divided into 2 main categories: 1) competitive inhibitors and 2) noncompetitive inhibitors - with a third category, 3) uncompetitive inhibitors, rarely encountered.

    The importance of KI is that in all enzyme reactions where substrate, inhibitor, and enzyme interact, the normal Km and/or Vmax for substrate enzyme interaction appear to be altered. These changes are a consequence of the influence of Ki on the overall rate equation for the reaction. The effects of Ki are best observed in Lineweaver-Burk plots.

    Competitive inhibitors
    Competitive inhibitors always bind at the catalytic or active site of the enzyme. Most drugs that alter enzyme activity are of this type. Competitive inhibitors are especially attractive as clinical modulators of enzyme activity. A decreasing concentration of the inhibitor reverses the equilibrium restoring active-free enzyme. In addition, since substrate and competitive inhibitors both bind at the same site they compete with one another for binding. Raising the concentration of substrate, while holding the concentration of inhibitor constant, results in reversal of competitive inhibition.

    Since high concentrations of substrate can displace virtually all competitive inhibitor bound to the active site of an enzyme, it becomes apparent that Vmax is unchanged by competitive inhibitors. This characteristic of competitive inhibitors is reflected in the identical vertical-axis intercepts of Lineweaver-Burk plots, with and without inhibitor.

    Since attaining Vmax requires appreciably higher substrate concentrations in the presence of competitive inhibitor, Km is also higher, as demonstrated by the differing negative intercepts on the horizontal axis in panel B.

    Noncompetitive inhibitors
    Panel C illustrates that noncompetitive inhibitors appear to have no effect on the intercept at the x-axis implying that noncompetitive inhibitors have no effect on the Km of the enzymes they inhibit. Since noncompetitive inhibitors do not interfere in the equilibration of enzyme, substrate, and ES complexes, the Km's of Michaelis-Menten type enzymes are not expected to be affected by noncompetitive inhibitors, as demonstrated by x-axis intercepts in panel C. However, because complexes that contain inhibitor (ESI) are incapable of progressing to reaction products, the effect of a noncompetitive inhibitor is to reduce the concentration of ES complexes that can advance to product. Since Vmax = K2[Etotal], and the concentration of competent Etotal is diminished by the amount of ESI formed, noncompetitive inhibitors are expected to decreases Vmax, as illustrated by the y-axis intercepts in panel C.

    Uncompetitive inhibitors
    A corresponding analysis of uncompetitive inhibition leads to the expectation that these inhibitors should change the apparent values of Km as well as Vmax. Changing both constants leads to double reciprocal plots, in which intercepts on the x and y axes are proportionately changed; this lead to the production of parallel lines in inhibited and uninhibited reactions.

    Enzyme Kinetics and Nomenclature Rules-screen-shot-2016-07-31-at-9-17-17-pm-png

    Enzyme Kinetics and Nomenclature Rules-screen-shot-2016-07-31-at-9-17-33-pm-png
    Last edited by admin; Fri 25th November '16 at 3:50pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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