Feb 1, 2023 · Here we developed and validated a strategy to measure TCA cycle flux in tissues and tumours in mice, using isotope tracer infusion, mass spectrometry (MS) and quantitative modelling of the...

In this review, we revisit the TCA cycle, including its potential origins and the history of its discovery. We provide a detailed accounting of the requirements for sustained TCA cycle function and the critical regulatory nodes that can stimulate or constrain TCA cycle activity.

Oct 28, 2022 · 1. Explain the significance of the TCA cycle and its biological roles, including its role in catabolic and anabolic pathways. 2. Explain how the irreversible reaction catalyzed by the pyruvate dehydrogenase complex leads to the entry of acetyl-CoA into the TCA cycle and why acetyl-CoA cannot be used as a substrate for gluconeogenesis. 3.

The regulation of the TCA cycle and its constant feedback with OXPHOS is critical to keep the cells in a stable state. There are multiple positive and negative allosteric regulators that control the metabolic flux of the TCA cycle. NADH inhibits all the regulatory enzymes in the TCA cycle.

A key advantage of MIMOSA flux interrogations is the broad capacity to assess time-dependent positional labeling of multiple ordinates across the TCA cycle. Here, the flow of isotope transfer through mitochondrial reactions was modeled mathematically using the program CWave ( …

Nov 9, 2017 · We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine‐derived fluxes: Oxidation of glucose‐derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase.

Jun 15, 2021 · Here, we illustrate a functional axis between heme synthesis and heme export: heme efflux through the plasma membrane sustains heme synthesis, and implementation of the two processes down-modulates the tricarboxylic acid (TCA) cycle flux and oxidative phosphorylation.

This comprehensive map identifies discrete carbon entry points for oxidative reactions (blue), PC-driven anaplerosis (green), PEP/pyruvate cycling (red), and subsequent turns of the TCA cycle (orange) measured by specific steady-state isotopomeric relationships across sequential and serial reactions of the TCA cycle (Figures 3B–3D).

Sep 21, 2020 · Using isotope-labeling data in vivo across several experimental conditions, we construct multiple models of central carbon metabolism and develop methods based on metabolic flux analysis (MFA) to solve for the preferences of glucose, lactate, and other nutrients used in …

Nov 3, 2015 · Here, we present a comprehensive and direct platform to track the flow of mass isotope labels through the sequential reactions of glycolysis and the TCA cycle via mass isotopomeric multi-ordinate spectral analysis (MIMOSA). MIMOSA deciphers the glucose-dependent changes in oxidative and non-oxidative metabolic rates in cultured cells.