Ron Davis has just brought up red blood cell deformability as a possible issue in some patients with me/cfs. I was looking at research on deformability and there is a link to G6PD, so I thought it was worth resurfacing this old thread.
The paper below (Tang, 2015) shows that linkage, and also ties it into a lot of other familiar metabolic components, like NADPH, AMPK, glutathione, etc. I'm not educated enough in cellular biology to figure out how relevant this is, but I hope by posting it here someone with the relevant skills who had not seen this before can help us all understand things a little better!
https://www.ncbi.nlm.nih.gov/pubmed/25556665
Inability to maintain GSH pool in G6PD-deficient red cells causes futile AMPK activation and irreversible metabolic disturbance.
Tang HY1,
Ho HY,
Wu PR,
Chen SH,
Kuypers FA,
Cheng ML,
Chiu DT.
Author information
Abstract
AIMS:
Glucose 6-phosphate dehydrogenase (G6PD) is essential for maintenance of nicotinamide dinucleotide hydrogen phosphate (NADPH) levels and redox homeostasis. A number of drugs, such as antimalarial drugs, act to induce reactive oxygen species and hemolytic crisis in G6PD-deficient patients. We used diamide (DIA) to mimic drug-induced oxidative stress and studied how these drugs affect cellular metabolism using a metabolomic approach.
RESULTS:
There are a few differences in metabolome between red blood cells (RBCs) from normal and G6PD-deficient individuals. DIA causes modest changes in normal RBC metabolism. In contrast, there are significant changes in various biochemical pathways, namely glutathione (GSH) metabolism, purine metabolism, and glycolysis, in G6PD-deficient cells. GSH depletion is concomitant with a shift in energy metabolism. Adenosine monophosphate (AMP) and adenosine diphosphate (ADP) accumulation activates AMP protein kinase (AMPK) and increases entry of glucose into glycolysis. However, inhibition of pyruvate kinase (PK) reduces the efficacy of energy production.
Metabolic changes and protein oxidation occurs to a greater extent in G6PD-deficient RBCs than in normal cells, leading to severe irreversible loss of deformability of the former.
INNOVATION AND CONCLUSION:
Normal and G6PD-deficient RBCs differ in their responses to oxidants. Normal cells have adequate NADPH regeneration for maintenance of GSH pool. In contrast, G6PD-deficient cells are unable to regenerate enough NADPH under a stressful situation, and switch to biosynthetic pathway for GSH supply. Rapid GSH exhaustion causes energy crisis and futile AMPK activation. Our findings suggest that drug-induced oxidative stress differentially affects metabolism and metabolite signaling in normal and G6PD-deficient cells. It also provides an insight into the pathophysiology of acute hemolytic anemia in G6PD-deficient patients.