BH4
BH4 Uses, Dosage, Side Effects, Food Interaction and all others data.
BH4 (tetrahydrobiopterin or BH4) is a cofactor in the synthesis of nitric oxide. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase.
Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.
| Trade Name | BH4 |
| Availability | Prescription only |
| Generic | Sapropterin |
| Sapropterin Other Names | 6R-BH4, R-THBP, Sapropterin, Sapropterina, sapropterinum, Tetrahydrobiopterin |
| Related Drugs | Kuvan, Palynziq |
| Type | |
| Formula | C9H15N5O3 |
| Weight | Average: 241.2471 Monoisotopic: 241.117489371 |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
BH4 is a cofactor used as an adjunct to phenylalanine restriction in the treatment of phenylketonuria (PKU).
For the treatment of tetrahydrobiopterin (BH4) deficiency.
BH4 is also used to associated treatment for these conditions: Phenylketonuria (PKU), Tetrahydrobiopterin Deficiencies
How BH4 works
Tetrahydrobiopterin (BH4) is a natural co-factor or co-enzyme for phenylalanine-4-hydroxylase (PAH),Tetrahydrobiopterine, and tryptophan-5-hydroxylase. Tetrahydrobiopterin is also a natural co-factor for nitrate oxide synthase. Therefore BH4 is required for the conversion of phenylalanine to tyrosine, for the production of epinephrine (adrenaline) and the synthesis of the monoamine neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production. As a coenzyme, BH4 reacts with molecular oxygen to form an active oxygen intermediate that can hydroxylate substrates. In the hydroxylation process, the co-enzyme loses two electrons and is regenerated in vivo in an NADH-dependent reaction. As a co-factor for PAH, tetrahydrobiopterin allows the conversion of phenylalanine to tyrosine and reduces the level of phenylalanine in the bloodstream, thereby reducing the toxic effects of of this amino acid. Normal serum concentrations of phenylalanine are 100 micomolar, while elevated (toxic) levels are typically >1200 micromolar. Individuals with a deficiency in tetrahydrobiopterin are not able to efficiently convert phenylalanine to tyrosine. The excess levels provided by tetrahydrobiopterin supplementation help improve enzyme efficiency. As a co-factor for tyrosine hydroxylase, BH4 facilitates the conversion of tyrosine to L-dopa while as a co-factor for tryptophan hydroxylase, BH4 allows the conversion of tryptophan to 5-hydroxytryptophan, which is then converted to serotonin.
Food Interaction
- Take at the same time every day.
- Take with food. Taking sapropterin with food increases oral absorption. BH4 may be dissolved in water, juice, or dispersed in applesauce.
[Moderate] ADJUST DOSING INTERVAL: Food increases the gastrointestinal absorption of sapropterin.
MANAGEMENT: BH4 should be administered with food, preferably at the same time each day.
BH4 tablets should be dissolved in 4 to 8 ounces (120 to 240 mL) of water or apple juice and taken within 15 minutes of dissolution.
BH4 Disease Interaction
Moderate: gastritis, liver impairment, neurological disorders, renal impairment
Innovators Monograph
You find simplified version here BH4
