Glycerol dehydrogenase
| glycerol dehydrogenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
ExPASy NiceZyme view | | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Glycerol dehydrogenase (
Structure
Glycerol dehydrogenase is a homooctamer composed of eight identical
Research into the structure of B. stearothermophilus shows that the active site contains a divalent cation—zinc ion, Zn2+. This zinc ion forms tetrahedral dipole interactions between the amino acid residues Asp173, His256, and His274 as well as a water molecule.
The NAD+ binding site, resembling the Rossmann fold within the N-terminal domain, extends from the surface of the enzyme to the cleft containing the active site. The nicotinamide ring (the active region of NAD+) binds in a pocket of the cleft consisting of the residues Asp100, Asp123, Ala124, Ser127, Leu129, Val131, Asp173, His174, and Phe247.
Finally, the substrate binding site consists of the residues Asp123, His256, His274 as well as a water molecule.[9]
Function
Encoded by the gene gldA, the enzyme glycerol dehydrogenase, GlyDH catalyzes the oxidation of glycerol to glycerone. Unlike more common pathways utilizing glycerol, GlyDH effectively oxidizes glycerol in anaerobic metabolic pathways under ATP-independent conditions (a useful mechanism in the breakdown of glycerol in bacteria). In addition, GlyDH selectively oxidizes the C2 hydroxyl group to form a ketone rather than a terminal hydroxyl group to form an aldehyde.[10]
Mechanism
While the precise mechanism of this specific enzyme has not yet been characterized, kinetic studies support that GlyDH catalysis of the chemical reaction
- glycerol + NAD+ glycerone + NADH + H+
is comparable to those of other alcohol dehydrogenases. Therefore, the following mechanism offers a reasonable representation of glycerol oxidation by NAD+.
After NAD+ is bound to the enzyme, glycerol substrate binds to the active site in such a way as to have two coordinated interactions between two adjacent hydroxyl groups and the neighboring zinc ion. GlyDH then catalyzes the base-assisted deprotonation of the C2 hydroxyl group, forming an alkoxide. The zinc atom further serves to stabilize the negative charge on the alkoxide intermediate before the excess electron density around the charged oxygen atom shifts to form a double bond with the C2 carbon atom. Hydride is subsequently removed from the secondary carbon and acts as a nucleophile in electron transfer to the NAD+ nicotinamide ring. As a result, the H+ removed by the base is released as a proton into the surrounding solution; followed by the release of the product glycerone, then NADH by GlyDH.[11]
Industrial implications
As a result of increasing biodiesel production, formation of the byproduct, crude glycerol, has also increased. While glycerol is commonly used in food, pharmaceuticals, cosmetics, and other industries, increased production of crude glycerol has become very expensive to purify and utilize in these industries. Because of this, researchers are interested in finding new economical ways to utilize low-grade glycerol products. Biotechnology is one such technique: using particular enzymes to break down crude glycerol to form products such as 1,3-propanediol, 1,2-propanediol, succinic acid, dihydroxyacetone (glycerone), hydrogen, polyglycerols, and polyesters. As a catalyst for the conversion of glycerol to glycerone, glycerol dehydrogenase is one such enzyme being investigated for this industrial purpose.[12]
See also
References
- Notes
- PMID 1339360.
- ISSN 1350-0872.
- ISSN 0002-7863.
- PMID 14417009.
- PMID 14406375.
- PMID 647848.
- ISSN 0018-4888.
- PMID 2493267.
- PMID 11566129.
- PMID 7981227.
- PMID 16756501.
- ^ Pachauri, Naresh; He, Brian. (July 2006). "Value-added Utilization of Crude Glycerol from Biodiesel Production: A Survey of Current Research Activities" (PDF). American Society of Agricultural and Biological Engineers.
- Bibliography
- Asnis RE, Brodie AF (1953). "A glycerol dehydrogenase from Escherichia coli". J. Biol. Chem. 203 (1): 153–9. PMID 13069498.
- Burton RM; Kaplan NO (1953). "A DPN specific glycerol dehydrogenase from Aerobacter aerogenes". J. Am. Chem. Soc. 75 (4): 1005–1007. .
- Lin ECC; Magasanik B (1960). "The activation of glycerol dehydrogenase from Aerobacter aerogenes by monovalent cations". J. Biol. Chem. 235: 1820–1823. PMID 14417009.
