Glycerol 3-phosphate is produced by the cytosolic glycerol 3-phosphate dehydrogenase pathway. Cytosolic glycerol 3-phosphate dehydrogenase (GPDH) consumes NADH to produce glycolol 3-phosphate from dihydroxyacetone phosphate (DHAP). The generated glycolol 3-phosphate can cross the permeable outer mitochondrial membrane[1]. Glycerol 3-phosphate is unstable in its free form, and its stable salt form sn-Glycerol 3-phosphate lithium (GC61482) with the same biological activity is recommended.
Glycerol 3-phosphate alone can inhibit the proliferation of DU145 and A549 cells in a concentration-dependent manner, and Glycerol 3-phosphate can increase the sensitivity of cells to metformin. When the concentration of Glycerol 3-phosphate is equal to or less than 1mmol/L, it has no adverse effect on the oxygen consumption rate (OCR) of DU145 and A549 cells, but as the concentration of Glycerol 3-phosphate increases (10, 100mmol/L), OCR begins to be inhibited[2].
In C57Bl/6J mice, plasma intact fibroblast growth factor 23 (iFGF23) and C-terminal FGF23 (cFGF23) levels showed a dose-dependent increase after a single intraperitoneal injection of Glycerol 3-phosphate (50, 150 and 300mg/kg). Glycerol 3-phosphate increased the urine phosphate/creatinine ratio and decreased plasma 1,25-dihydroxyvitamin D3 levels[3]. In a myocardial ischemia-reperfusion (I/R) mouse model, glycerol 3-phosphate reduced myocardial infarction area (42 ± 2%) compared with the control group (56 ± 4%) by activating the quinone pool (Q-pool) to stimulate the production of ROS in complex III (antimycin A)[4].
References:
[1] Shen W, Wei Y, Dauk M, et al. Involvement of a glycerol-3-phosphate dehydrogenase in modulating the NADH/NAD+ ratio provides evidence of a mitochondrial glycerol-3-phosphate shuttle in Arabidopsis[J]. The Plant Cell, 2006, 18(2): 422-441.
[2] Xie J, Ye J, Cai Z, et al. GPD1 enhances the anticancer effects of metformin by synergistically increasing total cellular glycerol-3-phosphate[J]. Cancer research, 2020, 80(11): 2150-2162.
[3] Simic P, Kim W, Zhou W, et al. Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney[J]. The Journal of clinical investigation, 2020, 130(3): 1513-1526.
[4] Madungwe N B, Zilberstein N F, Feng Y, et al. Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart[J]. American journal of cardiovascular disease, 2016, 6(3): 93.