Folic acid and its metabolites seem to be particularly important in the recycling of BH4 and NOS coupling. Tetrahydrobiopterin is a cofactor for tryptophan hydroxylase (TPH) for the conversion of L-tryptophan (TRP) to 5-hydroxytryptophan (5-HTP). Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN),[2][3] is a cofactor of the three aromatic amino acid hydroxylase enzymes,[4] used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide syntheses. [18], Tetrahydrobiopterin has multiple roles in human biochemistry. For BH4-, we have 3 electrons for Boron, 1 for Hydrogen but we have 4 Hydrogens, and then we need to add one more for the negative charge, for a total of 3+4+1: 8 valence electrons. [35], GTPCH (GCH1) and tetrahydrobiopterin were found to have a secondary role protecting against cell death by ferroptosis in cellular models by limiting the formation of toxic lipid peroxides. Combination of tetrahydrobiopterin with levodopa can lead to increased excitability. Hydrogen only needs 2 valence electrons to have a full outer shell, so each of the Hydrogens has its outer shell full. [34], Depletion of tetrahydrobiopterin occurs in the hypoxic brain and leads to toxin production. The major one is to convert amino acids such as phenylalanine, tyrosine, and tryptophan to precursors of dopamine and serotonin, major monoamine neurotransmitters. BH4 can be oxidized by one or two electron reactions, to generate BH4 or BH3 radical and BH2, respectively. published a paper which concluded that it was safe, and also noted that "several clinical trials have suggested that treatment with BH4 improves ASD symptomatology in some individuals. Therefore, a deficiency in tetrahydrobiopterin can cause severe neurological issues related to a toxic buildup of L-phenylalanine. "[30], Since nitric oxide production is important in regulation of blood pressure and blood flow, thereby playing a significant role in cardiovascular diseases, tetrahydrobiopterin is a potential therapeutic target. Phenylalanine hydroxylase (PAH) catalyses the conversion of L-phenylalanine (PHE) to L-tyrosine (TYR). [29] In 2010, Frye et al. We have a total of 8 valence electrons. And the Boron has 8 valence electrons. Tetrahydrobiopterin was discovered to play a role as an enzymatic cofactor. Hydrogens always go on the outside, and we have 4 Hydrogens. Tyrosine hydroxylase (TH) catalyses the conversion of L-tyrosine to L-DOPA (DOPA), which is the precursor for dopamine. It works as a cofactor, being required for an enzyme's activity as a catalyst, mainly hydroxylases.[4]. [13] BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020. 70 More Lewis Dot Structures. We'll put 2 between atoms to form chemical bonds--we've used 6, and we've used all our valence electrons. Transcript: This is the BH4- Lewis structure. [24] Ascorbic acid is oxidized to dehydroascorbic acid during this process, although it can be recycled back to ascorbic acid. The role of BH4 in this enzymatic process is so critical that some research points to a deficiency of BH4 – and thus, of nitric oxide – as being a core cause of the neurovascular dysfunction that is the hallmark of circulation-related diseases such as diabetes.[20]. [citation needed], InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,4+,6-/m0/s1, "Sapropterin (Kuvan) Use During Pregnancy", "International Non-proprietary Names for Pharmaceutical Substances (INN)", "The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons", "Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis", "Kuvan- sapropterin dihydrochloride tablet Kuvan- sapropterin dihydrochloride powder, for solution Kuvan- sapropterin dihydrochloride powder, for solution", "Drug Approval Package: Kuvan (Sapropterin Dihydrochloride) NDA #022181", "Kuvan (sapropterin dihydrochloride) Tablets and Powder for Oral Solution for PKU", "Drug Approval Package: Kuvan Powder for Oral Solution (Sapropterin Dihydrochloride) NDA #205065", "How Focusing On Obscure Diseases Made BioMarin A $15 Billion Company", "BioMarin Announces Kuvan (sapropterin dihydrochloride) Patent Challenge Settlement", "What are common treatments for phenylketonuria (PKU)?