Sequestration of CoA and adaptation of CoA metabolism in MCAD-knockout cell and mouse models in response to energetic stress

Following on in silico and in vitro work, the effect of MCAD deficiency on CoA metabolism was investigated. Using a recently published HILIC-MS/MS method, free and acylated CoA species could be measured simultaneously in HepG2 MCAD-KO cells. The levels of CoA biosynthesis intermediates and total CoA was also characterised by HPLC in liver samples from MCAD-KO mice exposed to energetic stress (fasting adn cold). qPCR was applied to investigate changes in the CoA metabolism that might constitute reactions to an excessive degree of CoA sequestration. In silico modelling was used to hypothesise on the potential benefits of multifactorial, simultaneous adaptations as opposed to single-node adaptations.

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Created: 9th May 2025 at 14:23

Last updated: 16th May 2025 at 11:43

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