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![Relationship between substrate concentration and the rate
of an enzyme-catalysed reaction
rectangular
hyperbola
Maximal velocity (Vmax)
Maximum reaction rate (v
observed at saturating
substrate
concentrations) for a given
concentration of enzyme:
Vmax=¼ kcat[E]t.](https://image.slidesharecdn.com/biologiald234-240407090453-8ba03708/75/biologial-d-234-pdfy7ttyytyyt7iyfgiyyyy-7-2048.jpg)
![Competitive inhibition is usually caused by substances that are structurally
related to the substrate, and thus combine at the same binding site as the
substrate. The bindings are exclusive to each other, forming either an
enzyme–substrate (ES) or an enzyme–inhibitor (EI) complex but not a
ternary complex (EIS)
This type of inhibition can be completely overcome by high substrate
concentrations and thus does not affect the V. The Km is increased by a
factor of (1 + [I]/Ki). (Pharmacology, 2009)
______________________________________
Pharmacology, 2009. Competitive Inhibition.
https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition
Hyone-Myong Eun, in Enzymology Primer for Recombinant DNA Technology, 1996](https://image.slidesharecdn.com/biologiald234-240407090453-8ba03708/75/biologial-d-234-pdfy7ttyytyyt7iyfgiyyyy-22-2048.jpg)
biologial d 234.pdfy7ttyytyyt7iyfgiyyyy
- 1. Enzyme Substrate Complex ____________________________________ BiologyDictionary (2019), Enzyme Subtrate Complex https://biologydictionary.net/enzyme-substrate-complex/
- 2. There are twomodels used to describe the way enzymes interact with substrates: The 'lock and key’ model The ‘induced fit’ model ____________________________________ Bioninja https://ib.bioninja.com.au/higher-level/topic-8-metabolism-cell/untitled-6/models-of-action.html
- 3. ______________________________ E + S ES complex E + P
- 4. Enzymes are consideredto lower the activation energy of a system by making it energetically easier for the transition state to form. In the presence of an enzyme catalyst, the formation of the transition state is energetically more favourable (i.e. it requires less energy for the ‘kick start’), thereby accelerating the rate at which the reaction will proceed, but not fundamentally changing the energy levels of either the reactant or the product. ______________________________
- 7. Relationship between substrateconcentration and the rate of an enzyme-catalysed reaction rectangular hyperbola Maximal velocity (Vmax) Maximum reaction rate (v observed at saturating substrate concentrations) for a given concentration of enzyme: Vmax=¼ kcat[E]t.
- 9.
- 10. Michael- Menton Equation Plottingin the form of y = m(x) + C
- 11.
- 12. Inhibitors Some substances reduceor even stop the catalytic activity of enzymes in biochemical reactions. They block or distort the active site. These chemicals are called inhibitors, because they inhibit reaction. Inhibitors that occupy the active site and prevent a substrate molecule from binding to the enzyme are said to be active site-directed (or competitive, as they 'compete' with the substrate for the active site). Inhibitors that attach to other parts of the enzyme molecule, perhaps distorting its shape, are said to be non-active site-directed (or non competitive)
- 13. Reversible and irreversibleinhibitors are chemicals which bind to an enzyme to suppress its activity. One method to accomplish this is to almost permanently bind to an enzyme. These types of inhibitors are called irreversible. However, other chemicals can transiently bind to an enzyme. These are called reversible. Reversible inhibitors either bind to an active site (competitive inhibitors), or to another site on the enzyme (non-competitive inhibitors). (TeachMe Physiology, 2022) _____________________________________________ TeachMe Physiology, 2022. Enzyme Inhibition https://teachmephysiology.com/biochemistry/molecules-and-signalling/enzyme-inhibition/
- 14. Competitive Inhibition During CI , The inhibitor (I) competes with the substrate (S) for the enzyme active site (also known as the S-binding site). Binding of either of these molecules in the active site is a mutually exclusive event. • The substrate and inhibitor share a high degree of structural similarity. However, the inhibitor cannot proceed through the reaction to produce product. • Increasing the concentration of substrate will outcompete the inhibitor for binding to the enzyme active site • A competitive reversible inhibitor can be identified by its characteristic effects upon kinetic data
- 15. Competitive Inhibition Competitive inhibitorscompete with the substrate at the active site, and therefore increase Km (the Michaelis-Menten constant). However, Vmax is unchanged because, with enough substrate concentration, the reaction can still complete. The graph plot of enzyme activity against substrate concentration would be shifted to the right due to the increase of the Km, whilst the Lineweaver-Burke plot would be steeper when compared with no inhibitor.
- 16. Competitive Inhibition The expressionfor the Michaelis-Menten expression in the presence of a reversible competitive inhibitor is:
- 17.
- 18. Competitive Inhibition Inhibitor resemblesthe substrate and thus competes with it for the binding site at the active center of the enzyme. Inhibitor binds at the active center, blocking the substrate from interacting with the binding site. Inhibitor can be overcome through an excess of the substrate ; therefore, this inhibition is reversible. Decreases affinity of the enzyme for the substrate As affinity decreases, the Km value increases, since an increased Substrate concentration is required to obtain the half-maximal velocity. Vmax is not changed, however. ( Lecturio,2022) _____________________________________________ Lecturio, 2022 https://www.lecturio.com/concepts/enzyme-inhibition/
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- 20.
- 21. Comparison between inhibitors (TeachmePhysiology, 2022)
- 22. Competitive inhibition isusually caused by substances that are structurally related to the substrate, and thus combine at the same binding site as the substrate. The bindings are exclusive to each other, forming either an enzyme–substrate (ES) or an enzyme–inhibitor (EI) complex but not a ternary complex (EIS) This type of inhibition can be completely overcome by high substrate concentrations and thus does not affect the V. The Km is increased by a factor of (1 + [I]/Ki). (Pharmacology, 2009) ______________________________________ Pharmacology, 2009. Competitive Inhibition. https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition Hyone-Myong Eun, in Enzymology Primer for Recombinant DNA Technology, 1996
- 23. ______________________________________ Pharmacology, 2009. CompetitiveInhibition. https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition Hyone-Myong Eun, in Enzymology Primer for Recombinant DNA Technology, 1996 John W. Pelley, in Elsevier's Integrated Review Biochemistry (Second Edition), 2012 An example of a competitive inhibitor is the antineoplastic drug methotrexate. Methotrexate has a structure similar to that of the vitamin folic acid. It acts by inhibiting the enzyme dihydrofolate reductase, preventing the regeneration of dihydrofolate from tetrahydrofolate. This interferes with DNA synthesis and blocks cell division in rapidly dividing cancer cells.
- 24. End of presentation Furtherreading https://www.slideshare.net/MahendraMahi28/riversible-enzyme- inhibitors