What is Tetrahydrobiopterin used for?
Tetrahydrobiopterin (BH4) is essential for the biosynthesis of dopamine, noradrenaline, and serotonin, which serve as cofactors for tyrosine hydroxylase (TH) and tryptophan hydroxylase. GTP cyclohydrolase (GCH) is the first and rate-limiting enzyme for BH4 biosynthesis.
What is tetrahydrobiopterin deficiency?
Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine.
How is BH4 deficiency treated?
Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and supplements of folinic acid in DHPR deficiency.
Is BH4 a Biopterin?
Compounds. Biopterin compounds found within the body include BH4, the free radical BH3, and BH2 (also a free radical).
Is Tetrahydrobiopterin an amino acid?
Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine ( …
How can I increase my BH4 level?
Folate enhances the binding of BH4 to NOS through a pteridine-binding domain and then 5-methyltetrahydrofolate facilitates the electron transfer by BH4 from the NOS reductase domain to the heme. Therefore, folic acid (FA) enhances the chemical synthesis and stabilization of BH4 (2).
What causes low BH4?
BH4 deficiency is caused by pathogenic variants in any one of several genes including the GCH1, PCBD1, PTS, and QDPR genes. It is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, and blood and urine tests.
How is Tetrahydrobiopterin made?
BH4 is formed from the abundant, simple molecule GTP in a three-step process, each step catalyzed by a different enzyme; GTP cyclohydrolase I (encoded for by the gene GCH1), pyruvoyltetrahydropterin synthase (PTS) and sepiapterin reductase (SPR).
What is Dihydropteridine reductase?
Dihydropteridine reductase deficiency (DHPR) is a severe form of hyperphenylalaninemia (high levels of the amino acid phenylalanine in the blood) due to impaired renewal of a substance known as tetrahydrobiopterin (BH4).
Does tryptophan make you happy?
Research in the early 1970s showed that taking tryptophan supplements can boost serotonin, a neurotransmitter that was historically associated with feelings of well-being and happiness.
Can you eat potatoes with PKU?
Vegetables: Starchy vegetables like white, sweet, purple potatoes (and fries), winter squash, corn, and peas should be eaten sparingly. Most other fresh or frozen vegetables are low in phenylalanine with the exception of the ones on the non-compliant list.
How do you test for BH4 deficiency?
Molecular genetic testing can confirm a diagnosis of these disorders. Molecular genetic testing can detect mutations in the specific genes known to cause tetrahydrobiopterin deficiency. The test is often expensive and often not necessary to confirm a diagnosis of a disorder of tetrahydrobiopterin deficiency.
How BH4 is formed?
BH4 is formed de novo from GTP, via a sequence of enzymatic steps carried out by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl tetrahydropterin synthase (PTPS) and sepiapterin reductase (SR) [15].
What are types of phenylketonuria?
There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not have symptoms. Many countries have newborn screening programs for the disease.
What is tetrahydrobiopterin?
Tetrahydrobiopterin (BH4) is a naturally occurring essential cofactor for the conversion of a nitrogen component of l-arginine to NO by endothelial nitric oxide synthase (eNOS).
Can tetrahydrobiopterin cause hyperphenylalaninemia?
Summary. 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine…
What is the role of PTPs in tetrahydrobiopterin synthesis?
This reaction is the second step (shown above) in the biosynthesis of tetrahydrobiopterin from GTP, which is used as a cofactor in the synthesis of aromatic amino acid monooxygenases and nitric oxide synthase PTPS converts 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin (PTP) through the loss of the triphosphate group, a stereosp…
What happens when Tetrahydrobiopterin is deficient?
When tetrahydrobiopterin is deficient, the chemical balance within the body is upset. In most of these disorders, there are abnormally high levels of the amino acid phenylalanine (hyperphenylalaninemia). Amino acids such as phenylalanine are chemical building blocks of proteins and are essential for proper growth and development.