BH4–is it high or low in MECFS? Question of queuine

As pointed out by others there seems to be a discrepancy as to whether BH4 is high or low in MECFS.

High—this study looks legit
https://www.s4me.info/threads/detection-of-elevated-level-of-tetrahydrobiopterin-in-serum-samples-of-me-cfs-patients-with-orthostatic-intolerance-a-pilot-study-2023-gottschalk-ea.33317/


Or low? No data presented here

https://www.s4me.info/threads/genet...rs-of-bh4-deficiency-in-long-covid-omf.34882/

Seems like they should try to measure queuine

https://en.m.wikipedia.org/wiki/Queuine

“BH4 is a cofactor for the biopterin-dependent aromatic amino acid hydroxylaseenzymes, which catalyze the conversion of phenylalanine to tyrosine, tyrosine to L-DOPA, and tryptophan to 5-HTP, oxidizing BH4 to dihydrobiopterin (BH2) in the process. BH2 must then be converted back to BH4 by the enzyme dihydropteridine reductasebefore it can be used again. Queuine depletion appears to impair this "recycling" process, resulting in a deficit of BH4 and an excess of BH2, which in turn impairs the activity of the aromatic amino acid hydroxylase enzymes.[8]”

If BH4 is high then maybe queuine is not depleted? If BH4 is low then perhaps supplementing with queuine might help.

Anyway measuring queuine should help sort things out a bit.

 

Queuine, a bacterial-derived hypermodified nucleobase, shows protection in in vitromodels of neurodegeneration

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253216

Growing evidence suggests that human gut bacteria, which comprise the microbiome, are linked to several neurodegenerative disorders. An imbalance in the bacterial population in the gut of Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients has been detected in several studies. This dysbiosis very likely decreases or increases microbiome-derived molecules that are protective or detrimental, respectively, to the human body and those changes are communicated to the brain through the so-called ‘gut-brain-axis’. The microbiome-derived molecule queuine is a hypermodified nucleobase enriched in the brain and is exclusively produced by bacteria and salvaged by humans through their gut epithelium. Queuine replaces guanine at the wobble position (position 34) of tRNAs with GUN anticodons and promotes efficient cytoplasmic and mitochondrial mRNA translation. Queuine depletion leads to protein misfolding and activation of the endoplasmic reticulum stress and unfolded protein response pathways in mice and human cells. Protein aggregation and mitochondrial impairment are often associated with neural dysfunction and neurodegeneration. To elucidate whether queuine could facilitate protein folding and prevent aggregation and mitochondrial defects that lead to proteinopathy, we tested the effect of chemically synthesized queuine, STL-101, in several in vitro models of neurodegeneration. After neurons were pretreated with STL-101 we observed a significant decrease in hyperphosphorylated alpha-synuclein, a marker of alpha-synuclein aggregation in a PD model of synucleinopathy, as well as a decrease in tau hyperphosphorylation in an acute and a chronic model of AD. Additionally, an associated increase in neuronal survival was found in cells pretreated with STL-101 in both AD models as well as in a neurotoxic model of PD. Measurement of queuine in the plasma of 180 neurologically healthy individuals suggests that healthy humans maintain protective levels of queuine. Our work has identified a new role for queuine in neuroprotection uncovering a therapeutic potential for STL-101 in neurological disorders.

 

Seems like there will be some clarity on this issue in a couple of weeks……