Birrer Sandbox 2
Alcohol Dehydrogenase
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| 1htb, resolution 2.40Å () | |||||||||
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| Ligands: | , , , | ||||||||
| Gene: | HUMAN BETA3 CDNA (Homo sapiens) | ||||||||
| Activity: | Alcohol dehydrogenase, with EC number 1.1.1.1 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
OverviewOverview
Alcohol dehydrogenase (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, which is catalyzed by alcohol dehydrogenase.[1] ADH (PDB id 1htb) catalyzes the oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones through a mechanism that involves the removal of hydrogen.
StructureStructure
The initial scene () shows an overview of the molecule, allowing for a general look at the tertiary structure of alcohol dehydrogenase (it is complexed with cl, pyz, nad, and zn). A second scene () shows a close view of the ligand within each subunit. Acidic (negative) residues are selected as well as the NAD. The purple atom is Pyz 378; the green atom on the left is Cl 601, and Zn 375 is the small gray atom at the top.
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. It does contain at the N-terminal 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.[2]
Reaction and MechanismReaction and Mechanism
In the oxidation mechanism, ADH is momentarily associated with nicontinamide adenine dinucleotide (NAD+), which functions as a cosubstrate. In its reaction, alcohol dehydrogenase uses zinc and NAD to facilitate the reaction. The function of zinc is to position the –OH group on the ethanol in a conformation that allows for the oxidation to occur. NAD then acts as a cosubstrate and performs the oxidation. A second scene shows the whole molecule of ADH complexed with just Zn and EtOH (). A second scene () shows a picture of this interaction, with two ethanol molecules attached to the active sites. In the picture Zinc is positioned between Cys46, Cys174, and His67, all polar side chains. Ethanol, then, binds to the zinc which is next to the NAD cosubstrate. [3]
[4] The of alcohol dehydrogenase reaction is as follows: CH3CH2OH + NAD+ -> CH3COH (acetaldehyde) + NADH + H+ (Note: The reaction is actually reversible although the arrow does not show it) [5] The alcohol dehydrogenase reaction is a bisubstrate reaction, where ADH catalyzed the transfer of a hydride ion from ethanol to NAD+. In metabolic reactions within the human liver, glyceraldehyde is reduced to glycerol through a mechanism in which NADH is reduced to NAD+, and this whole process is catalyzed by alcohol dehydrogenase.
The Mechanism for alcohol dehydrogenase follows an Ordered bisubstrate mechanism. The mechanism, then, is pretty straight forward: the NAD+ and alcohol bind to the enzyme, so that the enzyme is now attached to the two subtrates. While attached, the hydrogen is formally transferred from the alcohol to NAD, resulting in the products NADH and a ketone or aldehyde. The two products are then released, and the enzyme has catalyzed the reaction.
Kinetics and RegulationKinetics and Regulation
Fill in
ReferencesReferences
- ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.
- ↑ 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>
- ↑ Alcohol Dehydrogenase. Protein Data Bank. 2010. RCSB. 1 March 2010 <http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb13_3.html>
- ↑ Robergs, Robert. "Exercise-Induced Metabolic Acidosis: Where do the Protons come from?". 2009. 2/27 2010. <http://www.sportsci.org/jour/0102/rar.htm>.
- ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.