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Cellular Nitrogen and Energy Metabolism in ME/CFS

This project aims to test the nitrogen hypothesis, which is that damaging, nitrogen-containing by-products of energy metabolism accumulate more readily in the cells of ME/CFS patients.

  • Christopher Armstrong, Phd
  • Paul Gooley, PhD
  • Daniel Missailidis, PhD
  • Jo Cambridge, PhD
  • Neil McGregor, PhD
  • Blood-based immune cells from ME/CFS patients appear to die at a faster rate than healthy control cells. Interesting finding but it makes these cells difficult to use for the experiments we are conducting.
  • Lymphoblasts are a more stable and strong cell type that appear appropriate for our metabolism studies.
  • Distinct lipid and amino acid profiles couldbe seen between ME/CFS and controls in lysed lymphoblasts.
  • Data is being collected currently.
STUDY HYPOTHESIS AND DESCRIPTION

ME/CFS is diagnosed by its symptoms, which include post-exertional malaise, fatigue, and brain fog. It is unclear how these symptoms arise, and there are likely multiple routes to arrive at this chronic pathological state. However, there is a fundamental defect in energy metabolism in ME/CFS, which may be a common underlying cause of its symptoms.

We have hypothesized that reactive nitrogen by-products are accumulating in the cells of ME/CFS patients as a result of using amino acids for energy production in the mitochondria.To test this hypothesis, we will culture blood-based immune cells and feed them with labelled sugar, fats and amino acids. As the cells use the labelled sugar, fatand amino acids for energy production we will be able to monitor how their metabolism differs from healthy controls.

OBJECTIVES

  1. Develop method for conducting stable-isotopelabelled cellular metabolism studies.
  2. Observe where Nitrogen atoms flow during energy metabolism in cells from ME/CFS and controls.
  3. Assess the use of carbohydrates, amino acids and ketones by cells from ME/CFS and controls.

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