Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA.
Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Metabolism. 2022 Jul;132:155214. doi: 10.1016/j.metabol.2022.155214. Epub 2022 May 11.
Glycerol is a well-recognized substrate for new glucose production via gluconeogenesis in the liver. However, its carbon contribution to the glycolytic intermediate lactate is not known in humans.
Here we infused stable isotope tracers C-glycerol and 6,6-D-glucose into six metabolically healthy individuals after an overnight fast to study glycerol metabolism and measure glucose rate of appearance. Serum samples underwent liquid chromatography-mass spectrometry analysis.
Glycerol and glucose rates of appearance were 2.21 ± 1.42 μmol/kg/min and 7.81 ± 1.15 μmol/kg/min, respectively. Under steady-state conditions, the C enrichment for lactate was significantly higher than that of glucose (2.90 ± 0.52% versus 1.53 ± 0.78%, p = 0.017), suggesting direct glycerol to lactate metabolism. The percentage of lactate derived from glycerol was also significantly higher than the percentage of glucose (13.88 ± 2.69% versus 6.50 ± 2.59%, p = 0.005).
Given that lactate itself is a carbon source for gluconeogenesis and tricycarboxylic cycle intermediates, glycerol's ability to donate carbons to lactate may make it quantitatively more important to intermediary metabolism than currently appreciated.
甘油是肝脏中糖异生作用产生新葡萄糖的公认底物。然而,其碳对人乳酸这一糖酵解中间产物的贡献尚不清楚。
本研究在禁食过夜后,将稳定同位素示踪剂 C-甘油和 6,6-D-葡萄糖注入六名代谢健康的个体,以研究甘油代谢并测量葡萄糖出现率。血清样本进行液相色谱-质谱分析。
甘油和葡萄糖的出现率分别为 2.21 ± 1.42 μmol/kg/min 和 7.81 ± 1.15 μmol/kg/min。在稳态条件下,乳酸的 C 丰度明显高于葡萄糖(2.90 ± 0.52%比 1.53 ± 0.78%,p = 0.017),提示存在直接的甘油向乳酸的代谢。甘油衍生的乳酸百分比也明显高于葡萄糖(13.88 ± 2.69%比 6.50 ± 2.59%,p = 0.005)。
鉴于乳酸本身就是糖异生和三羧酸循环中间产物的碳源,甘油向乳酸供碳的能力可能使其对中间代谢的重要性比目前认识的更为量化。