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BH4
Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the metabolism 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 synthases. Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (quinonoid dihydrobiopterin). Tetrahydrobiopterin is available as a tablet for oral administration in the form of sapropterin dihydrochloride (BH4*2HCL). It was approved for use in the United States as a tablet in December 2007 and as a powder in December 2013. It was approved for use in the European Union in December 2008, Canada in April 2010, and Japan in July 2008. It is sold under the brand names Kuvan and Biopten. The typical cost of treating ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tetrahydrobiopterin Deficiency
Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems. In healthy individuals, it is metabolised (hydroxylated) into tyrosine, another amino acid, by phenylalanine hydroxylase. However, this enzyme requires tetrahydrobiopterin as a cofactor and thus its deficiency slows phenylalanine metabolism. High levels of phenylalanine are present from infancy in people with untreated tetrahydrobiopterin (THB, BH4) deficiency. The resulting signs and symptoms range from mild to severe. Mild complications may include temporary low muscle tone. Severe complications include intellectual disability, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperatur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenylketonuria
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight. Phenylketonuria is an inherited genetic disorder. It is caused by mutations in the '' PAH'' gene, which can result in inefficient or nonfunctional phenylalanine hydroxylase, an enzyme responsible for the metabolism of excess phenylalanine. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop. The two main types are classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not ha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aromatic Amino Acid Hydroxylase
Biopterin-dependent aromatic amino acid hydroxylases (AAAH) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase (), tyrosine 3-hydroxylase (), and tryptophan 5-hydroxylase (). These enzymes primarily hydroxylate the amino acids L-phenylalanine, L-tyrosine, and L-tryptophan, respectively. The AAAH enzymes are functionally and structurally related proteins which act as rate-limiting catalysts for important metabolic pathways. Each AAAH enzyme contains iron and catalyzes the ring hydroxylation of aromatic amino acids using tetrahydrobiopterin (BH4) as a substrate. The AAAH enzymes are regulated by phosphorylation at serines in their N-termini. Role in metabolism In humans, phenylalanine hydroxylase deficiency can cause phenylketonuria, the most common inborn error of amino acid metabolism. Phenylalanine hydroxylase catalyzes the conversion of to . Tyrosine hydroxylase catalyzes the rate-limiting step in catecholamine biosynthesis ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administration can be easier and less painful than other routes of administration, such as Injection (medicine), injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth". The expression is used in medicine to describe a treatment that is taken orally (but not ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Trimethoprim
Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia in people with HIV/AIDS. It is taken orally (swallowed by mouth). Common side effects include nausea, changes in taste, and rash. Rarely it may result in blood problems such as not enough platelets or white blood cells. Trimethoprim may cause sun sensitivity. There is evidence of potential harm during pregnancy in some animals but not humans. It works by blocking folate metabolism via dihydrofolate reductase in some bacteria, preventing creation of bacterial DNA and RNA and leading to bacterial cell death. Trimethoprim was first used in 1962. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Medical uses It is primarily used in the treatment of urinary tract infectio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Methotrexate
Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given Oral administration, by mouth or by injection. Common side effects include nausea, feeling tired, fever, increased risk of infection, leukopenia, low white blood cell counts, and ulcerative stomatitis, breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dihydrofolate Reductase Inhibitor
A dihydrofolate reductase inhibitor (DHFR inhibitor) is a molecule that inhibits the function of dihydrofolate reductase, and is a type of antifolate. Since folate is needed by rapidly dividing cells to make thymine, this effect may be used to therapeutic advantage. For example, methotrexate is used as cancer chemotherapy because it can prevent neoplastic cells from dividing. Bacteria also need DHFR to grow and multiply and hence inhibitors selective for bacterial vs. host DHFR have found application as antibacterial agents. Classes of small-molecules employed as inhibitors of dihydrofolate reductase include diaminoquinazoline and diaminopyrroloquinazoline, Most of the above specified inhibitors are structural analogues of the substrate dihydrofolate and bind to the active site of the enzyme. Further, it has been recently shown that, in ''E. coli'' DHFR, allosteric site binders can inhibit the enzyme either uncompetitively or non-competitively. The examples provided below are sp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adverse Effects
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
National Organization For Rare Disorders
The National Organization for Rare Disorders (NORD) is a nonprofit organization, based in Connecticut, aiming to provide support for individuals with rare diseases by advocating and funding research, education, and networking among service providers. It was founded in 1983 by Abbey Meyers, along with individuals and rare diseases leaders of rare disease support groups, and it is a 501(c)(3) tax exempt organization. History The organization grew out of an "informal coalition" of support groups and families called together in the late 1970s to advocate legislation supporting development of orphan drugs, or drugs for treating rare diseases. They succeeded in getting the United States Congress to pass the Orphan Drug Act (ODA) in early 1983. The initial coalition was led by Abbey Meyers, whose son had Tourette syndrome. Tourette syndrome was estimated by the National Institutes of Health to affect 100,000 people in the United States. Meyers' son was helped by an experimental dru ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GTP Cyclohydrolase I
GTP cyclohydrolase I (GTPCH) () is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP). Gene GTPCH is encoded by the gene ''GCH1''. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme. Clinical significance At least 94 disease-causing mutations in this gene have been discovered. Mutations in this gene are associated with two disorders: autosomal recessive GTP cyclohydrolase I deficiency and autosomal dominant GTP cyclohydrolase I deficiency. These may present with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA) and lead to a lack of certain neurotransmitters (dopamine, norepinephrine, epinephrine and serotonin). The dominant form, w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
