代谢物
平衡
分解代谢
柠檬酸循环
化学
氨基酸
丙氨酸
焊剂(冶金)
葡萄糖稳态
新陈代谢
内生
丝氨酸
生物化学
内科学
内分泌学
生物
胰岛素
酶
有机化学
医学
胰岛素抵抗
作者
Xiaoxuan Li,Sheng Hui,Emily T. Mirek,William Jonsson,Tracy G. Anthony,Won Dong Lee,Xianfeng Zeng,Cholsoon Jang,Joshua D. Rabinowitz
标识
DOI:10.1038/s42255-021-00517-1
摘要
Homeostasis maintains serum metabolites within physiological ranges. For glucose, this requires insulin, which suppresses glucose production while accelerating its consumption. For other circulating metabolites, a comparable master regulator has yet to be discovered. Here we show that, in mice, many circulating metabolites are cleared via the tricarboxylic acid cycle (TCA) cycle in linear proportionality to their circulating concentration. Abundant circulating metabolites (essential amino acids, serine, alanine, citrate, 3-hydroxybutyrate) were administered intravenously in perturbative amounts and their fluxes were measured using isotope labelling. The increased circulating concentrations induced by the perturbative infusions hardly altered production fluxes while linearly enhancing consumption fluxes and TCA contributions. The same mass action relationship between concentration and consumption flux largely held across feeding, fasting and high- and low-protein diets, with amino acid homeostasis during fasting further supported by enhanced endogenous protein catabolism. Thus, despite the copious regulatory machinery in mammals, circulating metabolite homeostasis is achieved substantially through mass action-driven oxidation.
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