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6-Pyruvoyltetrahydropterin Synthase Deficiency
6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. It is a recessive disorder that is accompanied by hyperphenylalaninemia. Commonly reported symptoms are initial truncal hypotonia, subsequent appendicular hypertonia, bradykinesia, cogwheel rigidity (neurology), rigidity, generalized dystonia, and marked diurnal fluctuation. Other reported clinical features include difficulty in swallowing, oculogyric crises, somnolence, irritability, hyperthermia, and seizures. Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported. Patients with mild phenotypes may deteriorate if given folate antagonists such as methotrexate, which can interfere with a salvage pathway through which dihydrobiopterin is converted into tetrahydrobiopterin via dihydrofolate reductase. Treatment options include substitution with neurotransmitter precursors (levodopa, 5 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hyperphenylalaninemia
Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ( he are routinely screened in newborns by the neonatal heel prick (Guthrie test), which takes a few drops of blood from the heel of the infant. Standard heconcentrations in unaffected persons are about 60 µM: heconcentrations in persons with untreated phenylketonuria may be many times that (600µM to 2400µM), which indicate that the child is at risk for severe intellectual disability. Phenylketonuria is classed as an autosomal recessive condition: in heterozygous form, heshows a moderate elevation, perhaps two-fold over that of unaffected homozygotes, which is classified as hyperphenylalaninemia ('' hyper-'' + ''phenylalanine'' + '' -emia'' = high hein blood). Symptoms and signs The coloration of the skin, hair, and eyes is different ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Folate Antagonists
Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR). Comparison of available agents Mechanism Many are primarily DHFR inhibitors, but raltitrexed is an inhibitor of thymidylate synthase, and pemetrexed inhibits both and a third enzyme. Antifolates act specifically during DNA and RNA synthesis, and thus are cytotoxic during the S-phase of the cell cycle. Thus, they have a greater toxic effect on rapidly dividing cells (such ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the skin pigment melanin. It is encoded by the codons UUU and UUC. Phenylalanine is found naturally in the milk of mammals. It is used in the manufacture of food and drink products and sold as a nutritional supplement for its analgesic and antidepressant effects. It is a direct precursor to the neuromodulator phenethylamine, a commonly used dietary supplement. As an essential amino acid, phenylalanine is n ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor (chemistry), precursor chemical, L-DOPA, which is biosynthesis, synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopaminergic pathway, dopamine pathways, one of which plays a major role in the motivational component of reward system, reward-motivated behavior. The anticipa ... [...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] |
International Working Group On Neurotransmitter Related Disorders
The International Working Group on Neurotransmitter Related Disorders is an international collaboration of researchers studying neurotransmitter disorders. It has created a patient registry for longitudinal studies. The group studies deficiencies in aromatic amino acid decarboxylase, tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase A, dopamine transporter, vesicular monoamine transporter 2 GTP cyclohydrolase (Segawa disease), 6-Pyruvoyltetrahydropterin synthase deficiency, 6-pyruvoyl-tetrahydropterin synthase, dihydropteridine reductase, sepiapterin reductase, folate receptor alpha, dihydrofolate reductase, 3-phosphoglycerate dehydrogenase, 3-phosphoserine phosphatase, phosphoserine aminotransferase, the glycine cleavage system (the deficiency is called glycine encephalopathy or non-ketotic hyperglycinaemia), GABA-transaminase, and Succinic semialdehyde dehydrogenase deficiency, succinate-semialdehyde dehydroxylase. References External links Rare diseases P ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
J Child Neurol
The ''Journal of Child Neurology'' is a peer-reviewed medical journal that covers the field of pediatric neurology. The editor-in-chief is Marc C. Patterson ( Mayo Clinic). The journal was established in 1986 and is published by Sage Publications. Abstracting and indexing The journal is abstracted and indexed in Scopus and the Science Citation Index Expanded. According to the ''Journal Citation Reports'', its 2012 impact factor The impact factor (IF) or journal impact factor (JIF) of an academic journal is a scientometric index calculated by Clarivate that reflects the yearly mean number of citations of articles published in the last two years in a given journal, as ... is 1.668. References External links * {{Official website, http://www.sagepub.com/journals/Journal201859/title SAGE Publishing academic journals English-language journals Monthly journals Publications established in 1986 Neurology journals Pediatrics journals ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders. Reversible inhibitors of monoamine oxidase A (RIMAs) are a subclass of MAOIs that selectively and reversibly inhibit the MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia. Due to their reversibility, they are safer in single-drug overdose than the older, irreversible MAOIs, and weaker in increasing the monoamines important in depressive disorder. RIMAs have not gained widespread market share in the United States. Medical uses MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, ... [...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] |
Levodopa
-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 enant ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dihydrofolate Reductase
Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the ''DHFR'' gene. It is found in the q11→q22 region of chromosome 5. Bacterial species possess distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar. Structure A central eight-stranded beta-pleated sheet makes up the main feature of the polypeptide backbone folding of DHFR. Seven of these strands are parallel and the eighth runs antiparallel. Four alpha helices connect successive beta strands. Residues 9 – 24 are termed "Met20" or "loop 1" and, along with other loops, are part of the major subdomain that surround the active site. The active site is situated in the N-terminal half of the sequence, which includes a conse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
