Preprint Systems Modeling Reveals Shared Metabolic Dysregulation and Novel Therapeutic Treatments in ME/CFS and Long COVID, 2024, Gong-Hua et al

[Midnattsol]

Aspartate/Asparigine are amino acids that have also been seen to change with diet. Increased asparigine and lower aspartate is associated with «healthier» dietary patterns with more vegetables, nuts and other fibre rich foods and lower junk foods. This would be a diet with more antioxidants, which makes sense since oxidative agents could influence the change between aspartate/asparagine.

 

[MelbME]

I should add that Aspartate has one N atom.

This N atom in Aspartate is actually the N in NO.

I don't think a lot of people realise how simple this is even in metabolism field. But 99%+ of Nitric Oxide molecules gets the N from aspartate.

 

[mariovitali]

I just realised that asparagine is directly related to N-Linked Glycosylation (I will inform Wenzhong Xiao and his team about this). N-Linked glycosylation is one of the first targets identified by machine learning. If ER Stress is indeed a problem in ME/CFS patients, disruption of N-Linked glycosylation could be the cause of it.

Entry of Wikipedia for Asparagine :



Blog post on N-Linked Glycosylation (October 2017)

http://algogenomics.blogspot.com/2017/10/latest-network-analysis-results.html


As always, I communicated these targets and the potential use of N-Acetyl Glucosamine (NAG) to several ME/CFS researchers in 2017. Interestingly, NAG may be helpful for some patients but caution is advised :

 

[MerryB]

The fact that this is a preprint, data taken from small cohorts, and other potential methodological issues aside - this paper caught my eye because I've noted amino acid metabolism alterations as suggested findings in a few different studies now...

My urine urea output is about 50 % of the lower end of normal (according to 24 hour urine tests), for no explained reason. It may not be related, but findings like this catch my eye as I do ponder whether this could be related to some inefficiency of nitrogen metabolism, and whether this could be related to my ME symptoms. I will be interested to see whether this avenue is supported by further research.

 

[Dolphin]

https://www.biorxiv.org/content/10.1101/2024.06.17.599450v2

Revision:

Systems Modeling Reveals Shared Metabolic Dysregulation and Novel Therapeutic Treatments in ME/CFS and Long COVID
Gong-Hua Li, Feifei Han, Efthymios Kalafatis, Qing-Peng Kong, Wenzhong Xiao
This article is a preprint and has not been certified by peer review [what does this mean?].


Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex, multisystem conditions that pose significant challenges in healthcare.

Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions.

This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway.

Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies.

In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood.

Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials.

https://twitter.com/user/status/1856687593993191872

 

[mariovitali]

I would like to Thank Dr Wenzhong Xiao for including me as a co-author in the paper and also point the attention of researchers to the mention of N-Linked glycosylation due to low asparagine levels.


From the paper :

The consistent down-regulation of specific metabolic pathways across both indications suggests a fundamental disruption in amino acid metabolism and energy metabolism, which could be contributing to the severity and persistence of patients’ symptoms. In addition, Asparagine provides key sites for N-linked glycosylation, which is required for proper protein folding in the endoplasmic reticulum (ER), and otherwise may induce ER stress, which likely takes place in ME/CFS

A proposed intervention for patients was forwarded to Dr Xiao last week which does not involve LOLA or TUDCA.