Muuttuuko tetrahydrobiopteriini vitamiiniksi COVID-10 taudissa?

BH₄ is a cofactor for the generation of nitric oxide in the CNS, which is a neurotransmitter/modulator. Deficiency of BH₄ causes severe autonomic irregularities and mental retardation and, ultimately, is not compatible with life. Severe cardiopulmonary dysrhythmia, fluctuating blood pressure, sleep irregularities, and early unexpected death may be explained by these considerations.

Hyvin normaalissa ja tasapainoisesa tilanteessa  tetrahydrobiopteriini on kehossa mudosotuva  molekyyli, joten siltä on karissut  vitamiinin maine, mikä folihapolla on.  Sen funktioalue  on  molekulaarista happea tarvitsevaa aluetta ja  se vastaa myös  aivojen NO- synteesistä osaltaan.
 https://www.sciencedirect.com/topics/neuroscience/biopterin

 Kerta toisensa jlkeen  olen pohtinut  tämän molekyylin  vitamiiniominaisuuksia. Pitäisikö sen saanti varmistaa.

Tarkistan genomin  geeniresurssit:

Select item 5092 PCBD1 ID: 5092	pterin-4 alpha-carbinolamine dehydratase 1 [Homo sapiens (human)]	Chromosome 10, NC_000010.11 (70882280..70888565, complement)	DCOH, PCBD, PCD, PHS	126090
Select item 5805 PTS ID: 5805	6-pyruvoyltetrahydropterin synthase [Homo sapiens (human)]	Chromosome 11, NC_000011.10 (112226428..112233973)	PTPS	612719
Select item 84105 PCBD2 ID: 84105	pterin-4 alpha-carbinolamine dehydratase 2 [Homo sapiens (human)]	Chromosome 5, NC_000005.10 (134905131..134962644)	DCOH2, DCOHM, PH

 PTS, PTPS (11q23.1)
https://www.ncbi.nlm.nih.gov/gene/5805
The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008] Expression Ubiquitous expression in adrenal (RPKM 23.3), kidney (RPKM 11.8) and 25 other tissues See more

Biochim Biophys Acta. 2004 Jan 5;1670(1):56-68.

6-pyruvoyl tetrahydropterin synthase (PTPS). Folate derivatives are essential cofactors in the biosynthesis of purines, pyrimidines, and amino acids, as well as formyl-tRNA. Mammalian cells are able to utilize pre-formed folates after uptake by a carrier-mediated active transport system. Most microbes and plants lack this system and must synthesize folates de novo from guanosine triphosphate. One enzyme from this pathway is PTPS which catalyzes the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin. The functional enzyme is a hexamer of identical subunits.

• Structure:1B66_A; PTPS binds dihydroneopterin triphosphate and Zn2+
  - View structure with Cn3D

Nuclear localization of tetrahydrobiopterin biosynthetic enzymes.

Elzaouk L¹, Laufs S, et al. Abstract

Biosynthesis of the tetrahydrobiopterin (BH(4)) cofactor, essential for catecholamines and serotonin production and nitric oxide synthase (NOS) activity, requires the enzymes GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR). Upon studying the distribution of GTPCH and PTPS with polyclonal immune sera in cross sections of rat brain, prominent nuclear staining in many neurons was observed besides strong staining in peri-ventricular structures. Furthermore, localization studies in transgenic mice expressing a Pts-LacZ gene fusion containing the N-terminal 35 amino acids of PTPS revealed beta-galactosidase in the nucleus of neurons. In contrast, PTPS-beta-galactosidase was exclusively cytoplasmic in the convoluted kidney tubules but nuclear in other parts of the nephron, indicating again that nuclear targeting may occur only in specific cell categories. Furthermore, the N terminus of PTPS acts as a domain able to target the PTPS-beta-galactosidase fusion protein to the nucleus. In transiently transfected COS-1 cells, which do not express GTPCH and PTPS endogenously, we found cytoplasmic and nuclear staining for GTPCH and PTPS. To further investigate nuclear localization of all three BH(4)-biosynthetic enzymes, we expressed Flag-fusion proteins in transiently transfected COS-1 cells and analyzed the distribution by immunolocalization and sub-cellular fractionation using anti-Flag antibodies and enzymatic assays. Whereas 5-10% of total GTPCH and PTPS and approximately 1% of total SR were present in the nucleus, only GTPCH was confirmed to be an active enzyme in nuclear fractions. The in vitro studies together with the tissue staining corroborate specific nuclear localization of BH(4)-biosynthetic proteins with yet unknown biological function.