SNPs for GTP Cyclohydrolase I (GCH1), rate-limiting enzyme for BH4 - relation to NOS

[mariovitali]

@nandixon

Thank you for your detailed answer and the time you put aside for writing it. I am fully recovered from CFS but i want to make sure that i will do everything possible to have BH4 at optimal levels since low BH4 may contribute to Endoplasmic Reticulum Stress.

 

[pemone]

BH4 is important in the production of neurotransmitters and also for regulation of the enzyme nitric oxide synthase (NOS). NOS can potentially become dysregulated ("uncoupled") when BH4 is deficient and produce too much nitric oxide and superoxide, leading to peroxynitrite and, theoretically, exacerbating the chronically high levels of oxidative stress that are seen in CFS/ME.

I think you reversed the causality here. BH4 is a cofactor to nitric oxide synthase. Having more BH4 promotes more nitric oxide production. Low BH4 levels would suggest you might have low nitric oxide. Likewise, uncoupling of NOS is typically associated with low nitric oxide not high. Here is a nice study that discusses this issue.

 

[nandixon]

@pemone

Yes, you're right. Where I wrote “...when BH4 is deficient and produce too much nitric oxide and superoxide, leading to peroxynitrite…” that should just be “...when BH4 is deficient and produce superoxide, leading to peroxynitrite…”