In 2006, Costigan, Woolf and colleagues showed in Nature Medicine that people with variants of the gene for GTP cyclohydrolase
(GCH1)-about 2 percent of the population-are at markedly lower risk for chronic pain.
Sauna therapy can act via two distinct mechanisms to raise the levels of BH4, acting in both cases by raising the levels of the enzyme GTP cyclohydrolase
I (GPCH), the first and rate-limiting enzyme in the de novo synthesis pathway for BH4.
3] Human genes: CYP2C19, cytochrome P450, family 2, subfamily C, polypepetide 19; GCH1, GTP cyclohydrolase
1; TH, tyrosine hydroxylase; SPR, sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase); PML, promyelocytic leukemia; RARA, retinoic acid receptor, alpha.
The company made equally rapid progress in optimizing inhibitors of the enzyme GTP cyclohydrolase
1 (GCH1), a key target within the BH4 synthesis pathway, and in identifying additional promising drug targets.
The Punch locus of Drosophila encodes GTP cyclohydrolase
I, a multimeric enzyme that catalyzes the first step in pterin biosynthesis.
These diseases include: GTP Cyclohydrolase
I Deficiency (dopa responsive dystonia) and Tyrosine Hydroxylase Deficiency (both currently treatable), Aromatic L Amino Acid Decarboxylase Deficiency, and Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency.
sauna therapy Acts to increase BH4 Trials availabiity; mechanism published on via increased synthesis MCS, FM and of GTP cyclohydrolase
An exception is found in dominantly inherited GTP cyclohydrolase
deficiency (doparesponsive dystonia) (15); in this disorder, it appears that the major impact is on the dopaminergic system, as an isolated decrease in HVA is observed (16).
4% of alleles in the study population) of the GTP cyclohydrolase
gene (dopa-responsive dystonia, GCH1) and lower degrees of persistent pain after back surgery.
In the published experiments, mice dependent upon daily injections of L-dopa for their survival, were injected with AAV vectors carrying the tyrosine hydroxylase and GTP cyclohydrolase
I genes directly to the striatum, one of the principal regions of the brain affected in Parkinson's disease.
A haplotype in the GTP cyclohydrolase
1 (dopa-responsive dystonia) gene (GCH1)  [(1), Fig.
Mutations in the GTP cyclohydrolase
I and 6-pyruvoyl-tetrahydropterin synthase genes.