All About BH4

[hiconscience]

so I have began reading up on BH4 and it is extremely interesting to me. I am wondering what others have uncovered and if they have used BH4 supplementally. it helps create dopamine out of tyrosine lowers free tryptophan. Exogenous estrogen lower BH4... I am also wondering it's effects on growth and the pituitary. Since it helps make dopamine I would think it would lower prolactin formation in the pituitary. also wondering it's effects on liver since it is a B vitamin technically I would think it would be positive.
any input or what to expect from supplementation would be much appreciated!

CPC #9: HASHIMOTO's AND MELASMA: GATEWAY DISEASES - Dr. Jack Kruse
-Holly

 

[managing]

bump

 

[goodandevil]

so I have began reading up on BH4 and it is extremely interesting to me. I am wondering what others have uncovered and if they have used BH4 supplementally. it helps create dopamine out of tyrosine lowers free tryptophan. Exogenous estrogen lower BH4... I am also wondering it's effects on growth and the pituitary. Since it helps make dopamine I would think it would lower prolactin formation in the pituitary. also wondering it's effects on liver since it is a B vitamin technically I would think it would be positive.
any input or what to expect from supplementation would be much appreciated!

CPC #9: HASHIMOTO's AND MELASMA: GATEWAY DISEASES - Dr. Jack Kruse
-Holly

Did you find any more information?

 

[Amazoniac]

I'm not familiar with these, but decided to share anyway because I realized there isn't much information posted on them.

- Nutrient Metabolism: Structures, Functions, and Genes (978-0-12-387784-0)

Queunine

"The queuosine nucleoside base influences the growth and differentiation of colonic enterocytes."

"Most or all queuine comes from normal intestinal flora. It is likely to be essential, since a specific enzyme exists for its incorporation into certain tRNAs; however, the health consequences of reduced production due to a disturbance or elimination of intestinal bacteria (antibiotics, low-fiber diet) are not known."

"Queuine deficiency interferes with efficient conversion of phenylalanine to tyrosine due to a lack of tetrahydrobiopterin (Rakovich et al., 2011). Tyrosine-deficient animals that lack a queuine source (because they are germ free) die within a few weeks. [?] Interaction of queuine deficiency with a lack of other nutrients or metabolic inefficiencies is possible since tetrahydrobiopterin is a cofactor for further enzymes, particularly tyrosine hydroxylase (EC1.14.16.2), tryptophan hydroxylase (EC1.14.16.4), and nitric oxide synthase (EC1.14.13.39)."

"Since queuine is essential for intestinal pathogens, such as Shigella flexneri, targeted inhibition of its synthesis might be promising (Gradler et al., 2001)."

- Prolonging healthy aging: Longevity vitamins and proteins
⬑ [102] The Queuine Micronutrient: Charting a Course from Microbe to Man​

Biopterin

"Biopterin is needed for the metabolism of phenylalanine, tyrosine, and tryptophan, and for the synthesis of hormones, neurotransmitters, and skin pigments (catecholamines, melanin, serotonin, and melanotonin), and cell signaling (nitric oxide). Roles in promoting angiogenesis, neuronal survival, and cellular immunity, and for protection against free radicals also are likely."

"The body can produce adequate amounts of biopterin in the absence of dietary intake; synthesis requires GTP, niacin, and magnesium." "This pathway accounts for about half of the BH4 synthesis in vivo. The remainder is generated through alternative pathways that rely on aldehyde reductase (EC1.1.1.21) and carbonyl reductase (EC1.1.1.184), some in conjunction with sepiapterin reductase."

"Lack of the nucleoside base queuine reduces tetrahydrobiopterine concentrations and is associated with an accumulation of dihydrobiopterine (Rakovich et al., 2011). Both of these metabolic changes reduce the activity of tetrahydrobiopterine-dependent enzymes."

"Forms present in food include tetrahydrobiopterin, dihydrobiopterin, and neopterin. The quantities available from specific foods or typical intake levels are not yet well characterized." "Some ingested tetrahydrobiopterin is absorbed, as demonstrated by the rapid lowering of phenylalanine levels in a patient with defective biopterin synthesis (Snyderman et al., 1987)."

"Inflammation and infection tend to depress availability of biopterin in tissues, such as endothelia of small blood vessels, due to rapid oxidation of the reduced form (McNeill and Channon, 2012)."

"Functions:

• Tyrosine synthesis: Phenylalanine can be the precursor of tyrosine through the action of the ferroenzyme phenylalanine hydroxylase (EC1.14.16.1). This hydroxylation of phenylalanine is driven by the oxidation of BH4 to 4a-hydroxytetrahydrobiopterin (4a-carbinolamine).
• Catecholamine and pigment synthesis: Synthesis of the catecholamines, dopamine, noradrenaline, and adrenaline is initiated by tyrosine 3-monooxygenase (EC1.14.16.2).
• Serotonin and melanotonin synthesis: Tryptophan hydroxylase (EC1.14.16.4) utilizes BH4 for the synthesis of serotonin and melatonin from l-tryptophan or tryptamin.
• Nitric oxide synthesis: All isoforms (NOS1, NOS2, NOS3) of nitric oxide synthase (EC1.14.13.39) require 1 mole of BH4 and 1 mole of heme per dimer as cofactors (Rafferty et al., 1999). Diminished BH4 synthesis and the resulting decrease in nitric oxide production have been suggested to contribute importantly to impaired angiogenesis (Marinos et al., 2001), as well as epithelial dysfunction and insufficient vasodilation (Gruhn et al., 2001). It has also been suggested that reduced availability of tetrahydrobiopterin increases the production of superoxide radicals instead of the normal NOS product nitric oxide, which may contribute to vascular dysfunction (McNeill and Channon, 2012).
• Cell growth and survival: Activation of neuronal Ca2+ channels (Koshimura et al., 1999) has been found to enhance neuronal survival. Whether biopterin actually affects the risk of Alzheimer’s disease, Parkinson’s disease, autism, or depression through this or another mechanism remains to be seen (Thöny et al., 2000). Dopaminergic neurons are specifically protected against free radical damage during periods of glutathione depletion by a tetrahydrobiopterin-dependent mechanism (Nakamura et al., 2000).
• Regulation of O-alkylated glycerolipids: Glyceryl-ether monooxygenase (EC1.14.16.5) is a microsomal enzyme that hydroxylates O-alkyl moieties in glycerolipids; the resulting hydroxyalkyl spontaneously breaks down into glycerol and a fatty aldehyde. Folic acid can serve as an electron donor instead of tetrahydropteridine.
• Immune defense: Increased neopterin levels are observed in patients with acute graft rejections, viral infections, auto-immune diseases, and several malignancies (Asano et al., 1997).
• Metabolic regulation: Tyrosinase activity is regulated by (6R)-l-erythro-5,6,7,8 tetrahydrobiopterin through specific allosteric inhibition (Schallreuter et al., 1999). Hydrogen peroxide inhibits the recycling of 6(R)-l-erythro-5,6,7,8-tetrahydrobiopterin by 4a-OH-tetrahydrobiopterin dehydratase and thereby might play an important role in the regulation of BH4-dependent enzymes (Schallreuter et al., 2001). Patches of skin affected by vitiligo are known to have abnormally high hydrogen peroxide concentrations, which accordingly would slow the recycling of 6(R)-l-erythro-5,6,7,8 tetrahydrobiopterin into BH4. Loss of skin pigmentation in vitiligo thus appears to occur due to the oxidized metabolite competitively, which inhibits epidermal phenylalanine hydroxylase and thus blocks the production of melanin (Schallreuter et al., 2001)."

 

[Amazoniac]

- Microbes and Monoamines: Potential Neuropsychiatric Consequences of Dysbiosis

Spoiler

[48] The second link on the previous post.

- Advanced Nutrition and Human Metabolism (978-1-133-10405-6)

"The first step in the degradation of phenylalanine (Figure 6.10) is specific to the liver and the kidneys. Phenylalanine is converted to tyrosine by the enzyme phenylalanine hydroxylase, also called a monooxygenase. This enzyme is iron dependent, and vitamin C and tetrahydrobiopterin are required for the reaction. Enzyme activity is regulated by phosphorylation/dephosphorylation with glucagon promoting phosphorylation and enzyme activity. Insulin has the opposite effect."

Spoiler

"Vitamin C, tetrahydrobiopterin, and oxygen are also involved in the hydroxylation of tryptophan for the synthesis of the neurotransmitter serotonin (5-hydroxytryptamine) in the brain (Figure 6.11). Tryptophan hydroxylase, also called monooxygenase, catalyzes the first step in serotonin synthesis, whereby tryptophan is converted to 5-hydroxytryptophan in a tetrahydrobiopterindependent reaction. Vitamin C may help regenerate the cosubstrate tetrahydrobiopterin from dihydrobiopterin. Subsequently, 5-hydroxytryptophan is decarboxylated in a vitamin B6–dependent reaction to generate serotonin."

Spoiler

 

[aliml]

Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification Get access​

Abstract​

Aims
Tetrahydrobiopterin (BH4) is a critical determinant of the biological function of endothelial nitric oxide synthase. The present study was to investigate the role of valvular endothelial cell (VEC)-derived BH4 in aortic valve calcification.
Methods and results
Plasma and aortic valve BH4 concentrations and the BH4:BH2 ratio were significantly lower in calcific aortic valve disease patients than in controls. There was a significant decrease of the two key enzymes of BH4 biosynthesis, guanosine 5′-triphosphate cyclohydrolase I (GCH1) and dihydrofolate reductase (DHFR), in calcified aortic valves compared with the normal ones. Endothelial cell-specific deficiency of Gch1 in Apoe−/− (Apoe−/−Gch1fl/flTie2Cre) mice showed a marked increase in transvalvular peak jet velocity, calcium deposition, runt-related transcription factor 2 (Runx2), dihydroethidium (DHE), and 3-nitrotyrosine (3-NT) levels in aortic valve leaflets compared with Apoe−/−Gch1fl/fl mice after a 24-week western diet (WD) challenge. Oxidized LDL (ox-LDL) induced osteoblastic differentiation of valvular interstitial cells (VICs) co-cultured with either si-GCH1- or si-DHFR-transfected VECs, while the effects could be abolished by BH4 supplementation. Deficiency of BH4 in VECs caused peroxynitrite formation increase and 3-NT protein increase under ox-LDL stimulation in VICs. SIN-1, the peroxynitrite generator, significantly up-regulated alkaline phosphatase (ALP) and Runx2 expression in VICs via tyrosine nitration of dynamin-related protein 1 (DRP1) at Y628. Finally, folic acid (FA) significantly attenuated aortic valve calcification in WD-fed Apoe−/− mice through increasing DHFR and salvaging BH4 biosynthesis.
Conclusion
The reduction in endothelial-dependent Tetrahydrobiopterin levels promoted peroxynitrite formation, which subsequently resulted in dynamin-related protein 1 tyrosine nitration and osteoblastic differentiation of valvular interstitial cells, thereby leading to aortic valve calcification. Supplementation of Folic Acid in diet attenuated hypercholesterolaemia-induced aortic valve calcification by salvaging Tetrahydrobiopterin bioavailability.

Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification

AbstractAims. Tetrahydrobiopterin (BH4) is a critical determinant of the biological function of endothelial nitric oxide synthase. The present study was to inve

academic.oup.com

Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase
High‑Dose Folic Acid Improves Endothelial Function By Increasing Tetrahydrobiopterin And Decreasing Homocysteine Levels

Buy Tetrahydrobiopterin (BH4) And Increase It Naturally — MyBioHack | Unlock Your Maximus Potential

BH4, or tetrahydrobiopterin, is used for many imperative and fundamental processes in the body.

mybiohack.com

 

[moa]

bh4 is the cure to colitis (IBS symptoms, Crohn, etc) according to a study in mice.

Tetrahydrobiopterin Attenuates DSS-evoked Colitis in Mice by Rebalancing Redox and Lipid Signalling

AbstractBackground and Aims: . Guanosine triphosphate cyclohydrolase [GCH1] governs the production of the enzyme cofactor tetrahydrobiopterin [BH4] which i

academic.oup.com

 

[Judd Crane]

I've tried it as a supplement. Works very well for mood, but pricey.

 

[moa]

taurine also seems to help with CuZnSOD, needed to protect bh4.

bioaviability of arginine also helps bh4 by using bh4 to produce NO with coupled eNOS enzyme instead of using these other enzyme, iNOS that can produce NO without the bed for bh4.

it seems citrulline supplementation could help with arginine availability, and it also can help with lowering ammonia (when CBS upregulation is the cause of low bh4).

I'm not sure how citrulline could be considered, as NO is not very peaty, considering it's role in blocking complex IV. on the other hand, only a small amount of arginine gets converted to NO, it's not there limiting factor, and citrulline is only a precursor anyway.

Taurine plays an important role in the protection of spermatogonia from oxidative stress - PubMed

It has been demonstrated that taurine has various physiological functions in the body. We demonstrated that taurine is abundant in the serum, liver, muscle and testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is found mainly in spermatogonia and is weakly expressed also...

pubmed.ncbi.nlm.nih.gov

@Judd Crane have you tried taurine or citrulline ?

I've just started yesterday with alpha lipoic acid 650mg, and it seems to work when taken with vitamin C, for my symptoms.

taurine is peaty, but citrulline I'm not sure.