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.
Glycerol 3-phosphate是由细胞溶质甘油3-磷酸脱氢酶途径产生的，胞质甘油3-磷酸脱氢酶（GPDH）消耗NADH从磷酸二羟基丙酮（DHAP）产生Glycerol 3-phosphate，生成的Glycerol 3-phosphate可穿过可渗透的线粒体外膜[1]。Glycerol 3-phosphate为游离形式化合物不稳定，推荐具有相同生物学活性的稳定盐形式sn-Glycerol 3-phosphate lithium（GC61482）。
单独使用Glycerol 3-phosphate能够以浓度依赖性的方式抑制DU145和A549细胞的增殖，并且Glycerol 3-phosphate可提高细胞对二甲双胍的敏感性。当Glycerol 3-phosphate浓度等于或小于1mmol/L时，对DU145和A549细胞的耗氧率（OCR）没有不利影响，但随着Glycerol 3-phosphate浓度的增加（10，100mmol/L），OCR开始受到抑制[2]。
在C57Bl/6J小鼠中，血浆完整的成纤维细胞生长因子23（iFGF23）和C末端FGF23（cFGF23）水平在单剂量Glycerol 3-phosphate（50, 150和300mg/kg）腹腔注射后表现出剂量依赖性增加。Glycerol 3-phosphate可增加尿磷酸盐/肌酐比值，降低血浆1,25-二羟基维生素D3水平[3]。在心肌缺血再灌注（ I/R ）小鼠模型中，与对照组（56 ± 4%）相比，Glycerol 3-phosphate可通过激活醌池（Q-pool）激发复合物III（抗霉素A）中ROS的产生从而减少心肌梗死面积 （42 ± 2%）[4]。