MetaCyc Pathway: glycerol-3-phosphate shuttle
Inferred from experiment

Enzyme View:

Pathway diagram: glycerol-3-phosphate shuttle

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 EnergyOther

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Homo sapiens, Saccharomyces cerevisiae

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 and a FAD-dependent mitochondrial glycerol-3-phosphate dehydrogenase (EC The cytosolic enzyme consumes NADH during the conversion of glycerone phosphate to sn-glycerol 3-phosphate, which can pass through the permeable mitochondrial outer membrane. sn-glycerol 3-phosphate is then reoxidized to glycerone 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 glycerone phosphate is subsequently channeled back to the cytosol. The shuttle operates in yeast [Ansell97, Larsson98], animals and plants [Shen06b].

Created 22-Dec-2008 by Caspi R, SRI International


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

Larsson98: 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

Shen06b: 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

Tobin80: Tobin A, Djerdjour B, Journet E, Neuburger M, Douce R (1980). "Effect of NAD on Malate Oxidation in Intact Plant Mitochondria." Plant Physiol 66(2);225-229. PMID: 16661409

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Albertyn92: Albertyn J, van Tonder A, Prior BA (1992). "Purification and characterization of glycerol-3-phosphate dehydrogenase of Saccharomyces cerevisiae." FEBS Lett 308(2);130-2. PMID: 1499720

Beleznai87: Beleznai Z, Jancsik V (1987). "Purification of L-3-glycerophosphate dehydrogenase from rat liver mitochondria." Biochem Int 15(1);55-63. PMID: 3134890

Boever76: Boever WJ, Kern T (1976). "Papillomas in black and white colobus monkeys (Colobus polykomus)." J Wildl Dis 12(2);180-1. PMID: 819665

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Cottingham80: Cottingham IR, Ragan CI (1980). "Purification and properties of L-3-glycerophosphate dehydrogenase from pig brain mitochondria." Biochem J 192(1);9-18. PMID: 6796038

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

Gong00: Gong Q, Brown LJ, MacDonald MJ (2000). "Functional analysis of two promoters for the human mitochondrial glycerol phosphate dehydrogenase gene." J Biol Chem 275(48);38012-21. PMID: 10954707

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

Kawamukai02: Kawamukai M (2002). "Biosynthesis, bioproduction and novel roles of ubiquinone." J Biosci Bioeng 94(6);511-7. PMID: 16233343

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lehn94: Lehn DA, Brown LJ, Simonson GD, Moran SM, MacDonald MJ (1994). "The sequence of a human mitochondrial glycerol-3-phosphate dehydrogenase-encoding cDNA." Gene 150(2);417-8. PMID: 7821823

MacDonald96: MacDonald MJ, Brown LJ (1996). "Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied." Arch Biochem Biophys 326(1);79-84. PMID: 8579375

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

Ou06: Ou X, Ji C, Han X, Zhao X, Li X, Mao Y, Wong LL, Bartlam M, Rao Z (2006). "Crystal structures of human glycerol 3-phosphate dehydrogenase 1 (GPD1)." J Mol Biol 357(3);858-69. PMID: 16460752

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

Robinson80: Robinson JJ, Weiner JH (1980). "The effect of amphipaths on the flavin-linked aerobic glycerol-3-phosphate dehydrogenase from Escherichia coli." Can J Biochem 58(10);1172-8. PMID: 6780164

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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