Glycerol-3-phosphate dehydrogenase
| Glycerol-3-phosphate dehydrogenase (NAD+) | |||||||||
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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-3-phosphate dehydrogenase (quinone) | |||||||||
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| Identifiers | |||||||||
ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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| NAD-dependent glycerol-3-phosphate dehydrogenase N-terminus | |||||||||
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| NAD-dependent glycerol-3-phosphate dehydrogenase C-terminus | |||||||||
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Glycerol-3-phosphate dehydrogenase (GPDH) is an enzyme that catalyzes the reversible redox conversion of dihydroxyacetone phosphate (a.k.a. glycerone phosphate, outdated) to sn-glycerol 3-phosphate.[2]
Glycerol-3-phosphate dehydrogenase serves as a major link between
Older terms for glycerol-3-phosphate dehydrogenase include alpha glycerol-3-phosphate dehydrogenase (alphaGPDH) and glycerolphosphate dehydrogenase (GPDH). However, glycerol-3-phosphate dehydrogenase is not the same as glyceraldehyde 3-phosphate dehydrogenase (GAPDH), whose substrate is an aldehyde not an alcohol.
Metabolic function
GPDH plays a major role in lipid
Reaction
The
One way to shuttle this reducing equivalent across the membrane is through the
- Cytosolic GPDH, or GPD1, is localized to the outer membrane of the mitochondria facing the glycerol-3-phosphate.
- In conjunction, Mitochondrial GPDH, or GPD2, is embedded on the outer surface of the glycerol-3-phosphate to dihydroxyacetone phosphate.[6]
The reactions catalyzed by cytosolic (soluble) and mitochondrial GPDH are as follows:
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Variants
There are two forms of GPDH:
| Enzyme | Protein | Gene | |||||
|---|---|---|---|---|---|---|---|
| EC number | Name | Donor / Acceptor | Name | Subcellular location | Abbreviation | Name | Symbol |
| 1.1.1.8 | glycerol-3-phosphate dehydrogenase | NADH / NAD+ | Glycerol-3-phosphate dehydrogenase [NAD+] | cytoplasmic | GPDH-C | glycerol-3-phosphate dehydrogenase 1 (soluble) | GPD1 |
| 1.1.5.3 | glycerol-3-phosphate dehydrogenase | quinol / quinone | Glycerol-3-phosphate dehydrogenase | mitochondrial | GPDH-M | glycerol-3-phosphate dehydrogenase 2 (mitochondrial) | GPD2 |
The following human genes encode proteins with GPDH enzymatic activity:
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GPD1
Cytosolic Glycerol-3-phosphate dehydrogenase (GPD1), is an
As a result,
GPD1 consists of two subunits,
Figure 4. The putative active site. The phosphate group of DHAP is half-encircled by the side-chain of Arg269, and interacts with Arg269 and Gly268 directly by hydrogen bonds (not shown). The conserved residues Lys204, Asn205, Asp260 and Thr264 form a stable hydrogen bonding network. The other hydrogen bonding network includes residues Lys120 and Asp260, as well as an ordered water molecule (with a B-factor of 16.4 Å2), which hydrogen bonds to Gly149 and Asn151 (not shown). In these two electrostatic networks, only the ε-NH3+ group of Lys204 is the nearest to the C2 atom of DHAP (3.4 Å).[1]
GPD2
Mitochondrial glycerol-3-phosphate dehydrogenase (GPD2), catalyzes the irreversible oxidation of
Response to environmental stresses
- Studies indicate that GPDH is mostly unaffected by pH changes: neither GPD1 or GPD2 is favored under certain pH conditions.
- At high salt concentrations (E.g. NaCl), GPD1 activity is enhanced over GPD2, since an increase in the salinity of the medium leads to an accumulation of glycerolin response.
- Changes in temperature do not appear to favor neither GPD1 nor GPD2.[11]
Glycerol-3-phosphate shuttle
The cytosolic together with the mitochondrial glycerol-3-phosphate dehydrogenase work in concert. Oxidation of cytoplasmic
The combined action of these enzymes maintains the
Role in disease
The fundamental role of GPDH in maintaining the
- Enhanced GPDH activity, particularly GPD2, leads to an increase in glycerol production. Since glycerol is a main subunit in lipid metabolism, its abundance can easily lead to an increase in triglyceride accumulation at a cellular level. As a result, there is a tendency to form adipose tissue leading to an accumulation of fat that favors obesity.[12]
- GPDH has also been found to play a role in arrythmia during infancy.[13]
Pharmacological target
The mitochondrial isoform of G3P dehydrogenase is thought to be inhibited by metformin, a first line drug for type 2 diabetes. [14]
Biological Research
Sarcophaga barbata was used to study the oxidation of L-3-glycerophosphate in mitochondria. It is found that the L-3-glycerophosphate does not enter the mitochondrial matrix, unlike pyruvate. This helps locate the L-3-glycerophosphate-flavoprotein oxidoreductase, which is on the inner membrane of the mitochondria.
Structure
Glycerol-3-phosphate dehydrogenase consists of two
See also
- substrate pages: glycerol 3-phosphate, dihydroxyacetone phosphate
- related topics: glycerol phosphate shuttle, creatine kinase, glycolysis, gluconeogenesis
References
- ^ PMID 16460752.
- PMID 16460752.
- ^ PMID 167714.
- ^ PMID 16891140.
- PMID 9171333.
- S2CID 19691537.
- ^ ISBN 0-7167-4684-0.
- S2CID 207194967. Archived from the originalon 2011-07-24. Retrieved 2011-05-16.
- PMID 15557339.
- S2CID 9248320.
- S2CID 41613712.
- PMID 21257036.
- PMID 17967976.
- PMID 25317875.
- PMID 10801498.
- PMID 25451934.
Further reading
- Baranowski T (1963). "α-Glycerophosphate dehydrogenase". In Boyer PD, Lardy H, Myrbäck K (eds.). The Enzymes (2nd ed.). New York: Academic Press. pp. 85–96.
- Brosemer RW, Kuhn RW (May 1969). "Comparative structural properties of honeybee and rabbit alpha-glycerophosphate dehydrogenases". Biochemistry. 8 (5): 2095–105. PMID 4307630.
- O'Brien SJ, MacIntyre RJ (Oct 1972). "The -glycerophosphate cycle in Drosophila melanogaster. I. Biochemical and developmental aspects". Biochemical Genetics. 7 (2): 141–61. S2CID 22009695.
- Warkentin DL, Fondy TP (Jul 1973). "Isolation and characterization of cytoplasmic L-glycerol-3-phosphate dehydrogenase from rabbit-renal-adipose tissue and its comparison with the skeletal-muscle enzyme". European Journal of Biochemistry. 36 (1): 97–109. PMID 4200180.
- Albertyn J, van Tonder A, Prior BA (Aug 1992). "Purification and characterization of glycerol-3-phosphate dehydrogenase of Saccharomyces cerevisiae". FEBS Letters. 308 (2): 130–2. S2CID 39643279.
- Koekemoer TC, Litthauer D, Oelofsen W (Jun 1995). "Isolation and characterization of adipose tissue glycerol-3-phosphate dehydrogenase". The International Journal of Biochemistry & Cell Biology. 27 (6): 625–32. PMID 7671141.
- Påhlman IL, Larsson C, Averét N, Bunoust O, Boubekeur S, Gustafsson L, Rigoulet M (Aug 2002). "Kinetic regulation of the mitochondrial glycerol-3-phosphate dehydrogenase by the external NADH dehydrogenase in Saccharomyces cerevisiae". The Journal of Biological Chemistry. 277 (31): 27991–5. PMID 12032156.
- Overkamp KM, Bakker BM, Kötter P, van Tuijl A, de Vries S, van Dijken JP, Pronk JT (May 2000). "In vivo analysis of the mechanisms for oxidation of cytosolic NADH by Saccharomyces cerevisiae mitochondria". Journal of Bacteriology. 182 (10): 2823–30. PMID 10781551.
- Dawson AG, Cooney GJ (Jul 1978). "Reconstruction of the alpha-glycerolphosphate shuttle using rat kidney mitochondria". FEBS Letters. 91 (2): 169–72. PMID 210038.
- Opperdoes FR, Borst P, Bakker S, Leene W (Jun 1977). "Localization of glycerol-3-phosphate oxidase in the mitochondrion and particulate NAD+-linked glycerol-3-phosphate dehydrogenase in the microbodies of the bloodstream form to Trypanosoma brucei". European Journal of Biochemistry. 76 (1): 29–39. PMID 142010.
- Eswaramoorthy S, Bonanno JB, Burley SK, Swaminathan S (Jun 2006). "Mechanism of action of a flavin-containing monooxygenase". Proceedings of the National Academy of Sciences of the United States of America. 103 (26): 9832–7. PMID 16777962.
External links
- equivalent entries:
- alphaGPDH at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- GPDH
- Yeast genome database GO term: GPDH Archived 2007-12-24 at the Wayback Machine
