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Dihydropteridine Reductase Deficiency
Dihydropteridine reductase deficiency (DHPRD) is a genetic disorder affecting the tetrahydrobiopterin (BH4) synthesis pathway, inherited in the autosomal recessive pattern. It is one of the six known disorders causing tetrahydrobiopterin deficiency, and occurs in patients with mutations of the QDPR gene. The disease presents with such symptoms as elevated levels of phenylalanine (hyperphenylalaninemia), microcephaly, hypotonus, mental retardation and epileptic seizures. Diagnostics Besides the traditional analysis of symptoms and investigation of phenylalanine concentrations, patients suspected for DHPRD undergo the assessment of enzymatic activity using the dried blood spot method - this permits to distinguish DHPR deficiency from the other forms of BH4 deficiency. Treatment Patients are prescribed a phenylalanine-reduced diet, with regular monitoring of phenylalanine levels in the blood. Besides the diet, a patient may be prescribed sapropterin, a synthetic analogue of tetrahyd ... [...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] |
TPH2
Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Until the discovery of TPH2 in 2003, serotonin levels in the central nervous system were believed to be regulated by serotonin synthesis in peripheral tissues, in which tryptophan hydroxylase is the dominant form. Function Tryptophan hydroxylase (TPH; EC 1.14.16.4) is the rate-limiting enzyme in the synthesis of serotonin (5-hydroxytryptamine, or 5HT). 5HT is causally involved in numerous central nervous activities, and it has several functions in peripheral tissues, including the maintenance of vascular tone and gut motility. upplied by OMIMref name="entrez"> Disabling this enzyme with drugs (especially p-chlorophenylalanine aka PCPA and Fenclonine) has allowed researchers to investigate the effects of very low serotonin levels on humans an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Folic Acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division. As humans cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements. Folate in the form of folic acid is used to treat anemia caused by folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby. Low levels in early pregnancy are believed to be the cause of more than half of babies born with NTDs. More than 80 countries use either mandatory or voluntary fortification of c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Folinic Acid
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein. Side effects may include trouble sleeping, allergic reactions, or fever. Use in pregnancy or breastfeeding is generally regarded as safe. When used for anemia it is recommended that pernicious anemia as a cause be ruled out first. Folinic acid is a form of folic acid that does not require activation by dihydrofolate reductase to be useful to the body. Folinic acid was first made in 1945. It is on the World Health Organization's List of Essential Medicines. Medical use Folinic acid is given following methotrexate as part of a total chemotherapeutic plan, where it may protect against bone marro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebral Folate Deficiency
Cerebral folate deficiency is a condition in which concentrations of 5-methyltetrahydrofolate are low in the brain as measured in the cerebral spinal fluid despite being normal in the blood. Symptoms typically appear at about 5 to 24 months of age. Without treatment there may be poor muscle tone, trouble with coordination, trouble talking, and seizures. One cause of cerebral folate deficiency is a mutation in a gene responsible for folate transport, specifically FOLR1. This is inherited in an autosomal recessive manner. Other causes appear to be Kearns–Sayre syndrome and autoantibodies to the folate receptor. For people with the FOLR1 mutation, even when the systemic deficiency is corrected by folate, the cerebral deficiency remains and must be treated with folinic acid. Success depends on early initiation of treatment and treatment for a long period of time. Fewer than 20 people with the FOLR1 defect have been described in the medical literature. Signs and symptoms Childr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-methyltetrahydrofolate
Levomefolic acid (INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6''S'')-5-methyltetrahydrofolate, and (6''S'')-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine. It is also the form found in circulation and transported across membranes into tissues and across the blood–brain barrier. In the cell, L-methylfolate is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon unit for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate, and must undergo enzymatic reduction by dihydrofolate reductase (DHFR) to become biologically active. It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivative of tet ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-hydroxytryptophan
5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. Uses 5-HTP is sold over the counter in the United States, Canada, Singapore, the Netherlands, and the United Kingdom as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. It is also marketed in many European countries for the indication of major depression under the trade names Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. A 2002 review concluded that although the data evaluated suggests that 5-HTP is more effective than placebo in the treatment of depression, the evidence was insufficient to be conclusive due to a lack of clinical data meeting the rigorous standards of the day. More and larger studies using current methodologies are needed to determine if 5-HTP is truly effective in treating depression. In small ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aromatic L-amino Acid Decarboxylase Inhibitor
An aromatic L-amino acid decarboxylase inhibitor (synonyms: DOPA decarboxylase inhibitor, Extracerebral decarboxylase inhibitor, DDCI and AAADI) is a medication of type enzyme inhibitor which inhibits the synthesis of dopamine by the enzyme aromatic L-amino acid decarboxylase (AADC, AAAD, or DOPA decarboxylase). It is used to inhibit the decarboxylation of L-DOPA to dopamine outside the brain, i.e. in the blood. This is primarily co-administered with L-DOPA to combat Parkinson's disease. Administration can prevent common side-effects, such as nausea and vomiting, as a result of interaction with D2 receptors in the vomiting center (or cheomoreceptor trigger zone) located outside the blood–brain barrier. Examples of extracerebral decarboxylase inhibitors include carbidopa and benserazide. Indications Peripherally selective DDCIs incapable of crossing the protective blood–brain barrier (BBB) are used in augmentation of L-DOPA (levodopa) in the treatment of Parkinson ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
QDPR
QDPR (quinoid dihydropteridine reductase) is a human gene that produces the enzyme quinoid dihydropteridine reductase. This enzyme is part of the pathway that recycles a substance called tetrahydrobiopterin, also known as BH4. Tetrahydrobiopterin works with an enzyme called phenylalanine hydroxylase to process a substance called phenylalanine. Phenylalanine is an amino acid (a building block of proteins) that is obtained through the diet; it is found in all proteins and in some artificial sweeteners. When tetrahydrobiopterin interacts with phenylalanine hydroxylase, tetrahydrobiopterin is altered and must be recycled to a usable form. The regeneration of this substance is critical for the proper processing of several other amino acids in the body. Tetrahydrobiopterin also helps produce certain chemicals in the brain called neurotransmitters, which transmit signals between nerve cells. The QDPR gene is located on the short (p) arm of chromosome 4 at position 15.31, from base pair ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
L-dopa
-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA, make it via biosynthesis from the amino acid -tyrosine. -DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, -DOPA itself mediates neurotrophic factor release by the brain and CNS. -DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia. -DOPA has a counterpart with opposite chirality, -DOPA. As is true for many molecules, the human body produces only one of these isomers (the -DOPA form). The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tetrahydrobiopterin
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 (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). Medical use 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 typica ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
