Enzymes 3 Lecture Notes PDF

International University of Africa Faculty of Medicine Department of Biochemistry Biochemistry – 1 Enzymes -3 By Dr. Mohammed Abdelrheem 5/10/2024 1  Inhibition of Enzyme Activity Enzymes inhibitors are comp...

International University of Africa Faculty of Medicine Department of Biochemistry Biochemistry – 1 Enzymes -3 By Dr. Mohammed Abdelrheem 5/10/2024 1  Inhibition of Enzyme Activity Enzymes inhibitors are compounds that decreases the velocity of the reaction by binding to the enzyme. They are two types: Reversible inhibitors. Irreversible inhibitors. 5/10/2024 Moh. Hamza 2  1- Reversible Inhibitors They are non covalent bound inhibitors (easy dissociate). Classified as: Competitive inhibitors: Inhibitors compete with the substrate for binding to the active site. The inhibitor resemble the substrate. 5/10/2024 Moh. Hamza 3  Increase the km value. Increase substrate concentration overcome competitive inhibition. The reaction is reversible. Example: Methotrexate (anticancer drug), is structural analogs of the natural substrate (Dihydropholate) for the Enzyme Dihydropholate reductase rapid cell death. 5/10/2024 Moh. Hamza 4  Competitive Inhibitors 5/10/2024 Moh. Hamza 5  Example of a competitive inhibitor Methotrexate (MTX) 5/10/2024 Moh. Hamza 6  Non competitive inhibitors: Inhibitors bind either the free enzyme or the ES complex at the different site. Not similar to substrate. No effect on Km. Decrease Vmax. Example: Cyanide (CN-) can noncompetitively inhibit the enzyme cytochrome oxidase (catalyse the binding of O2 with H to form water). 5/10/2024 Moh. Hamza 7  Noncompetitive Inhibitors 5/10/2024 Moh. Hamza 8  2- Irreversible Inhibitors Binds covalently or so tightly to the active site of the enzymes that they are inactivated irreversibly. 5/10/2024 Moh. Hamza 9  Allosteric Enzymes They are enzymes containing other sites (regulatory enzymes). The other sites bind activators (positive effectors) or inhibitors (negative effectors). Almost found at the first pathways, and catalyses irreversible reactions. 5/10/2024 Moh. Hamza 10 5/10/2024 Moh. Hamza 11  Isoenzymes Are enzymes that share the same substrate, but differ in: Their structure. Affinity to substrate. 5/10/2024 Moh. Hamza 12  Resistance to inhibitors. And mobility in electric fields (electrophoresis). Example: lactate dehydrogenase, consist of five isoenzymes (LDH1{H}, LDH2, LDH3, LDH4, and LDH5 {M}) all differ in the quaternary structure. 5/10/2024 Moh. Hamza 13  Lactate Dehydrogenase Isoenzymes 5/10/2024 Moh. Hamza 14  Regulation of Enzyme Activity Allosteric regulation: Feedback regulation Feed-forward regulation Covalent modification: Phosphorylation Dephosphorylation 5/10/2024 Moh. Hamza 15  Enzymes in Clinical Diagnosis Elevation of enzyme activity in plasma may indicate either the presence of a disease or damage to a specific tissues. Plasma enzymes are useful for diagnosis (activity) and prognosis (correlation). e.g. elevated level of Alanine aminotransferase (ALT) signals possible liver damage. 5/10/2024 Moh. Hamza 16  Good luck 5/10/2024 Moh. Hamza 17