What is cofactor BH4?
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).
How is BH4 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) .
What is BH4 supplement?
Tetrahydrobiopterin (BH4, sometimes THB) is a vital cofactor for numerous enzymes in the body, including those involved in the formation of nitric oxide (NO), and the key neurotransmitters dopamine, serotonin and epinephrine. BH4 plays a critical role in both heart and cognitive health.
Where does Tetrahydrobiopterin come from?
Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes provide instructions for making enzymes that help produce and recycle tetrahydrobiopterin in the body.
Why is phenylalanine converted to tyrosine?
Phenylalanine is an essential amino acid. To enter the tyrosine pathway, phenylalanine is converted into tyrosine by the enzyme phenylalanine hydroxylase, which has tetrahydrobiopterin as a cofactor. Deficiency of the enzyme or of its cofactor causes accumulation of phenylalanine in the body fluids and tissues.
What is BH4 deficiency?
Collapse Section. 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 do you test for BH4 deficiency?
Pterins, neurotransmitter metabolites and folates can be measured in cerebrospinal fluid (CSF). These tests can help to distinguish tetrahydrobiopterin deficiencies from one another and to assess the potential severity of the disease. Molecular genetic testing can confirm a diagnosis of these disorders.
What is Ptps deficiency?
6-pyruvoyl-tetrahydropterin synthase (PTPS) is a rare disorder caused by harmful genetic changes (mutations) in the PTS gene. The PTS gene is required to make tetrahydrobiopterin (BH4). Low levels of BH4 result in a condition called hyperphenylalaninemia, caused by toxic levels of the amino acid phenylalanine.
Can I take L tyrosine and phenylalanine together?
Adults should consume tyrosine and phenylalanine combined in an amount equal to 14 milligrams per kilogram of body weight per day. The two substances are combined because they work together in your body. If you eat a healthy, well-balanced diet, you don’t need to do the math.
What foods contain BH4?
From study period 2 onwards all BH4-sensitive patients increased their consumption of foods with a higher protein content such as bread, pasta, rice and dairy products as well as meat, egg and fish.
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.
Which is responsible for converting GTP to BH4?
Pathway diagram showing the three enzymes involved in converting GTP into BH4. As mentioned above, BH4 is an important cofactor for several enzymes including nitric oxide synthase ( NOS )1-3 which are responsible for converting arginine into nitric oxide (“NO”).
How does MTHF supplementation increase BH4 levels?
Rather, studies have shown that MTHF supplementation can increase BH4 levels by preventing its oxidation into BH2 and by supplementing BH4 activity with NOS enzymes further preventing its degradation. 17 18 Therefore, MTHF supplementation alone, or in conjunction with BH4, may prove beneficial to those with low levels of BH4.
Which is responsible for the recovery of BH4?
QDPR is the enzyme which is typically responsible for the recovery of BH4 from its reduced form BH2. 13 However, studies have also shown that the enzyme DHFR is also able perform this recovery activity. DHFR, like MTHFR, is an enzyme in the one carbon pathway, hence the similarity in their names. However, their action is rather different. 14
What is the role of BH4 in nitric oxide synthase?
As mentioned above, BH4 is an important cofactor for several enzymes including nitric oxide synthase ( NOS )1-3 which are responsible for converting arginine into nitric oxide (“NO”). BH4 is also the cofactor for tryptophan hydroxylase (TPH), which converts tryptophan into the neurotransmitter serotonin.