Glycerol 3-phosphate

Biosynthesis

Glycerol 3-phosphate is synthesized by reducing dihydroxyacetone phosphate (DHAP), an intermediate in glycolysis. The reduction is catalyzed by glycerol-3-phosphate dehydrogenase. DHAP and thus glycerol 3-phosphate can also be synthesized from amino acids and citric acid cycle intermediates via the glyceroneogenesis pathway. :[[File:Dihydroxyacetonphosphat Skelett.svg|x40px|DHAP]] + NAD(P)H + H+ → [[File:Glycerin-3-phosphat Skelett.svg|x40px|G1P]] + NAD(P)+

It is also synthesized by the phosphorylation of glycerol, which is generated by hydrolysis of fats. This esterification is catalyzed by glycerol kinase. :[[File:Glycerin Skelett2.svg|x40px|Glycerol]] + ATP → [[File:Glycerin-3-phosphat Skelett.svg|x40px|G3P]] + ADP

Metabolism and biological function

Glycerol 3-phosphate is a starting material for de novo synthesis of glycerolipids. In eukaryotes, it is first acylated on its sn-1 position by an ER- or mitochondrial membrane enzyme, glycerol-3-phosphate O-acyltransferase. A second acyl group is subsequently installed on the sn-2 position making phosphatidic acids. :[[File:Glycerin-3-phosphat Skelett.svg|x40px|G1P]] + Acyl-CoA → Lysophosphatidic acid + CoA

Glycerol-1-phosphatase catalyzes the hydrolysis of glycerol 3-phosphate to regenerate glycerol, allowing glycerol fermentation to produce glycerol from glucose through glycolysis pathway. A number of organisms express this enzyme. :[[File:Glycerin-3-phosphat Skelett.svg|x40px|G3P]] + H2O → [[File:Glycerin Skelett2.svg|x40px|Glycerol]] + Pi

Shuttle system

Main article: Glycerol 3-phosphate shuttle

Glycerol-3-phosphate dehydrogenases are located both in the cytosol and the intermembrane face of mitochondrial inner membrane. Glycerol 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) are molecules so small that they can permeate the mitochondrial outer membrane through porins and shuttle between two dehydrogenases. Using this shuttle system, NADH generated by cytosolic metabolisms including glycolysis is reoxidized to NAD+ reducing DHAP to G3P, and the reducing equivalent can be used for generating a proton gradient across the mitochondrial inner membrane by coupling and oxidizing G3P and reducing quinone.

The Glycerol 3-phosphate shuttle is an emergency back-up system to supply neurons' demand of energy.

Dephosphorylation

Main article: Phosphoglycolate phosphatase

Glycerol-3-phosphate was found to be a substrate for the enzyme phosphoglycolate phosphatase (PGP, or G3PP) in mammals in 2015.

Glycerol 1-phosphate

Glycerol 1-phosphate, sometimes called as D-glycerol 3-phosphate, is the enantiomer of glycerol 3-phosphate. Eukaryotes use the 3-phosphate, or L-configuration, for glycerolipid backbone. The 1-phosphate is specifically found in archaeal lipids.

Notes

References

1. "Nomenclature of Phosphorus-Containing Compounds of Biochemical Importance".
2. (January 2016). "Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic β-cells and hepatocytes". [[Proceedings of the National Academy of Sciences of the United States of America]].
3. (August 30, 2022). "Neuronal Back-up System Discovered".
4. (January 2022). "Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans". Nature Communications.
5. (2017). "Archaeal phospholipids: Structural properties and biosynthesis". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.