小柯机器人

美国耶鲁大学Gerald I. Shulman研究组开发出一种评估体内多种酶活的方法。2022年12月13日出，《细胞—代谢》杂志在线发表了这项成果。

Title: Q-Flux: A method to assess hepatic mitochondrial succinate dehydrogenase, methylmalonyl-CoA mutase, and glutaminase fluxes in vivo

Author: Brandon T. Hubbard, Traci E. LaMoia, Leigh Goedeke, Rafael C. Gaspar, Katrine D. Galsgaard, Mario Kahn, Graeme F. Mason, Gerald I. Shulman

Issue&Volume: 2022-12-13

Abstract: The mammalian succinate dehydrogenase (SDH) complex has recently been shown as capableof operating bidirectionally. Here, we develop a method (Q-Flux) capable of measuringabsolute rates of both forward (VSDH(F)) and reverse (VSDH(R)) flux through SDH in vivo while also deconvoluting the amount of glucose derived from four discreet carbonsources in the liver. In validation studies, a mitochondrial uncoupler increased netSDH flux by >100% in awake rodents but also increased SDH cycling. During hyperglucagonemia,attenuated pyruvate cycling enhances phosphoenolpyruvate carboxykinase efficiencyto drive increased gluconeogenesis, which is complemented by increased glutaminase(GLS) flux, methylmalonyl-CoA mutase (MUT) flux, and glycerol conversion to glucose.During hyperinsulinemic-euglycemic clamp, both pyruvate carboxylase and GLS are suppressed,while VSDH(R) is increased. Unstimulated MUT is a minor anaplerotic reaction but is readily inducedby small amounts of propionate, which elicits glucagon-like metabolic rewiring. Takentogether, Q-Flux yields a comprehensive picture of hepatic mitochondrial metabolismand should be broadly useful to researchers.

DOI: 10.1016/j.cmet.2022.11.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00502-2

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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