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

PoLiMeR is funded through the EU Marie Skłodowska-Curie Innovative Training Network (ITN), which drives scientific excellence and innovation. ITNs bring together universities, research institutes, industry and clinical partners from across the world to train researchers to doctorate level.

Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease ...

The behaviour of a published MCAD-KO HepG2 cell line was compared to that of a wild-type HepG2 cell line in terms of the changes in acyl-CoA and acylcarnitine levels (measured by HILIC-MS/MS) and gene expression pertaining to CoA metabolism (characterised by qPCR). Additionally, the incorporation of label from stable isotope-labelled pantothenate (vitamine B5) was over 24 hours of exposure to an energetic stressor was also investigated.

MCAD-KO mice (C57BL/6J background) were exposed to three different conditions: "fed", "fasting", and "fasting + cold". In this study we determined the concentration of various CoA biosynthetic intermediates (including CoA) and the expression of CoA metabolic genes in liver tissue samples from these groups of mice.

The expression of various genes related to the CoA metabolism as measured by qPCR.

Incorporation of stable isotope from pantothenate into total and free CoA pools.

Unzip model notebooks and keep in the same folder. Notebook "0, generate_model.nb" needs to be run before the others can be, as the model needs to be exported as Excel files before they cvan be used to make the figures.