This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: G3P shuttle, glycerol-3-P shuttle
|Superclasses:||Generation of Precursor Metabolites and Energy → Other|
Expected Taxonomic Range: Eukaryota
The rates of oxidation and reduction of NAD and NADH must be balanced for the continuation of both catabolism and anabolism. NADH, produced in the cytosol during glycolysis, need to be oxidized to NAD+. The net NADH oxidation process in the cell occurs primarily via mitochondrial respiration. However, NADH cannot traverse the inner mitochondrial membrane [Tobin80]. Therefore, cytosolic reducing equivalents must be transferred to the mitochondria through metabolite shuttles that operate between the two compartments.
One such shuttle is the glycerol-3-phosphate shuttle (G3P shuttle). This shuttle involves the combined actions of a cytoplasmic glycerol-3-phosphate dehydrogenase (NAD+) (EC 18.104.22.168) and a FAD-dependent mitochondrial glycerol-3-phosphate dehydrogenase (EC 22.214.171.124). The cytosolic enzyme consumes NADH during the conversion of dihydroxyacetone phosphate to sn-glycerol 3-phosphate, which can pass through the permeable mitochondrial outer membrane. sn-glycerol 3-phosphate is then reoxidized to dihydroxyacetone phosphate at the outer surface of the inner mitochondrial membrane by the mitochondrial FAD-dependent enzyme, which donates the electrons to the mitochondrial quinone pool. The dihydroxyacetone phosphate is subsequently channeled back to the cytosol. The shuttle operates in yeast [Ansell97, Larsson98a], animals and plants [Shen06a].
Ansell97: Ansell R, Granath K, Hohmann S, Thevelein JM, Adler L (1997). "The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation." EMBO J 16(9);2179-87. PMID: 9171333
Larsson98a: Larsson C, Pahlman IL, Ansell R, Rigoulet M, Adler L, Gustafsson L (1998). "The importance of the glycerol 3-phosphate shuttle during aerobic growth of Saccharomyces cerevisiae." Yeast 14(4);347-57. PMID: 9559543
Shen06a: Shen W, Wei Y, Dauk M, Tan Y, Taylor DC, Selvaraj G, Zou J (2006). "Involvement of a glycerol-3-phosphate dehydrogenase in modulating the NADH/NAD+ ratio provides evidence of a mitochondrial glycerol-3-phosphate shuttle in Arabidopsis." Plant Cell 18(2);422-41. PMID: 16415206
Cole78: Cole ES, Lepp CA, Holohan PD, Fondy TP (1978). "Isolation and characterization of flavin-linked glycerol-3-phosphate dehydrogenase from rabbit skeletal muscle mitochondria and comparison with the enzyme from rabbit brain." J Biol Chem 253(21);7952-9. PMID: 701295
Ferrer96: Ferrer J, Aoki M, Behn P, Nestorowicz A, Riggs A, Permutt MA (1996). "Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an alternatively spliced human islet-cell cDNA, tissue distribution, physical mapping, and identification of a polymorphic genetic marker." Diabetes 45(2);262-6. PMID: 8549872
Garrib86: Garrib A, McMurray WC (1986). "Purification and characterization of glycerol-3-phosphate dehydrogenase (flavin-linked) from rat liver mitochondria." J Biol Chem 261(17);8042-8. PMID: 3711123
Gudayol01: Gudayol M, Vidal J, Usac EF, Morales A, Fabregat ME, Fernandez-Checa JC, Novials A, Gomis R (2001). "Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus." Endocrine 16(1);39-42. PMID: 11822825
Menaya95: Menaya J, Gonzalez-Manchon C, Parrilla R, Ayuso MS (1995). "Molecular cloning, sequencing and expression of a cDNA encoding a human liver NAD-dependent alpha-glycerol-3-phosphate dehydrogenase." Biochim Biophys Acta 1262(1);91-4. PMID: 7772607
Prasad97: Prasad R, Zhadanov AB, Sedkov Y, Bullrich F, Druck T, Rallapalli R, Yano T, Alder H, Croce CM, Huebner K, Mazo A, Canaani E (1997). "Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax." Oncogene 15(5);549-60. PMID: 9247308
Rauchova97: Rauchova H, Fato R, Drahota Z, Lenaz G (1997). "Steady-state kinetics of reduction of coenzyme Q analogs by glycerol-3-phosphate dehydrogenase in brown adipose tissue mitochondria." Arch Biochem Biophys 344(1);235-41. PMID: 9244403
Ringler61: Ringler RL (1961). "Studies on the mitochondrial alpha-glycerophosphate dehydrogenase. II. Extraction and partial purification of the dehydrogenase from pig brain." J Biol Chem 236;1192-8. PMID: 13741763
Schryvers78: Schryvers A, Lohmeier E, Weiner JH (1978). "Chemical and functional properties of the native and reconstituted forms of the membrane-bound, aerobic glycerol-3-phosphate dehydrogenase of Escherichia coli." J Biol Chem 253(3);783-8. PMID: 340460
Showing only 20 references. To show more, press the button "Show all references".
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493