Birrer Sandbox 2: Difference between revisions
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==Overview== | ==Overview== | ||
Alcohol dehydrogenase (PDB id [[1htb]]), ADH, is an enzyme that catalyzes the 4th step in the metabolism of fructose before glycolysis. In the 4th step, glyceraldehyde is converted to the glycolytic intermediate DHAP by the NADH-dependent reduction to glycerol | Alcohol dehydrogenase (PDB id [[1htb]]), ADH, is an 80kDa enzyme that catalyzes the 4th step in the metabolism of fructose before glycolysis. In the 4th step, glyceraldehyde is converted to the glycolytic intermediate DHAP by the NADH-dependent, ADH catalyzed reduction to glycerol.<ref>Voet, et. al. ''Fundamentals of Biochemistry: 3rd Edition''. Hoboken: Wiley & Sons, Inc, 2008.</ref> ADH catalyzes the oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones through a mechanism that involves the removal of a hydrogen. | ||
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<scene name='Birrer_Sandbox_2/The_active_site/1'> | Within alcohol dehydrogenase, <scene name='Birrer_Sandbox_2/The_active_site/1'>the active</scene> site of alcohol dehydrogenase has three important residues, Phe 93, Leu 57, and Leu 116. These three residues work together to bind to the alcohol substrate.<ref>''Protein: Alcohol Dehydrogenase''. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm></ref> | ||
Zn plays an important role in the catalysis. It funtions by electrostatically stabilizing the oxygen in alcohol during | Zn plays an important role in the catalysis. It funtions by electrostatically stabilizing the oxygen in alcohol during the reaction, which causes the alcohol to be more acidic. At the <scene name='Birrer_Sandbox_2/Zinc_binding_site/1'>Zinc Binding Site</scene>, Zinc coordinates with Cys 146, Cys 174, and His 67.<ref>''Protein: Alcohol Dehydrogenase''. The College of Saint Benedict and Saint John's University. 1 March 2010 < http://www.users.csbsju.edu/~hjakubow/classes/rasmolchime/99ch331proj/alcoholdehydro/index.htm></ref> | ||
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Alcohol dehydrogenase exists as a dimer with a zinc molecule complexed in each of the subunits. It has a SCOP catagory of an alpha and beta protein. | Alcohol dehydrogenase exists as a dimer with a zinc molecule complexed in each of the subunits. It has a SCOP catagory of an alpha and beta protein. At the N-terminal, there is a domain that is all beta; however, the C-Terminal domain is alpha and beta, so the catagory is alpha and beta. The C-Terminal core has 3 layers of alpha/beta/alpha and parallel beta sheets of 6 strands.<ref>''Protein: Alcohol dehydrogenase from Human (Homo sapiens), different isozymes''. SCOP. 2009. 1 March 2010 < http://scop.berkeley.edu/data/scop.b.d.c.b.b.c.html></ref> | ||
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The alcohol dehydrogenase catalyzed aldehyde-NADH reaction show kinetics consistent with a random-order mechanism, and the rate-limiting step is the dissociation of the product enzyme-NAD+ complex. <ref>PMID: 4352908</ref> Alcohol dehydrogenase is more effective for smaller alcohol substrates, and it becomes less effective as substrate size increases. It is also more effective for primary than secondary alcohols.<ref>PMID: 4352908</ref> | The alcohol dehydrogenase catalyzed aldehyde-NADH reaction show kinetics consistent with a random-order mechanism, and the rate-limiting step is the dissociation of the product enzyme-NAD+ complex. <ref>PMID: 4352908</ref> Alcohol dehydrogenase is more effective for smaller alcohol substrates, and it becomes less effective as substrate size increases. It is also more effective for primary than secondary alcohols.<ref>PMID: 4352908</ref> In a study where ADH was immobilized in tresyl-chloride-activate agarose, it was shown that the Michaelis-Menten model could not take into consideration all the constraints induced by the immobilization on the enzyme properties but that the Theorell-Chance model was more appropriate.<ref>PMID: 3769934</ref> | ||
==Regulation== | ==Regulation== | ||
Substrate size is a regulator, where larger substrates inhibit alcohol dehydrogenase. Further, alcohol dehydrogenase is somewhat inhibited if the substrate is a secondary alcohol, as opposed to a primary alcohol. <ref>PMID: 4352908</ref> | Substrate size is a regulator, where larger substrates inhibit alcohol dehydrogenase. Further, alcohol dehydrogenase is somewhat inhibited if the substrate is a secondary alcohol, as opposed to a primary alcohol. <ref>PMID: 4352908</ref> Pyrazoles have also been shown to be inhibitors of ADH. <ref>PMID:115004</ref> Other inhibitors include heavy metals, thiourea, purine and pyrimidine derivatives, and both chloroethanol and flouroethanol. <ref>''Alcohol Dehydrogenase''. Worthington Biochemical Corporation . 31 March 2010 < http://http://www.worthington-biochem.com/ADH/default.html></ref> Activators include sulfhydryl activating reagents, mercaptoethanol, dithiothreitol, and cysteine.<ref>''Alcohol Dehydrogenase''.Worthington Biochemical Corporation . 31 March 2010 < http://http://www.worthington-biochem.com/ADH/default.html></ref> | ||