• On 16 December 2019, orphan designation EU/3/19/2229 was granted by the European Commission to BioMarin International Limited, Ireland, for adeno-associated virus vector encoding human phenylalanine hydroxylase (also known as BMN 307) for the treatment of phenylalanine hydroxylase deficiency. (europa.eu)
  • What is phenylalanine hydroxylase deficiency? (europa.eu)
  • Phenylalanine hydroxylase deficiency is a condition in which the body cannot process phenylalanine, an amino acid found in dietary proteins, because an enzyme called phenylalanine hydroxylase is lacking. (europa.eu)
  • Phenylalanine hydroxylase deficiency is debilitating in the long-term because of its effects on the brain in patients who are not treated. (europa.eu)
  • At the time of designation, phenylalanine hydroxylase deficiency affected less than 2 in 10,000 people in the European Union (EU). (europa.eu)
  • The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with phenylalanine hydroxylase deficiency. (europa.eu)
  • Patients with phenylalanine hydroxylase deficiency cannot process phenylalanine in the usual way because of mutations (changes) in the gene for the enzyme phenylalanine hydroxylase. (europa.eu)
  • At the time of submission of the application for orphan designation , no clinical trials with the medicine in patients with phenylalanine hydroxylase deficiency had been started. (europa.eu)
  • At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of phenylalanine hydroxylase deficiency or designated as an orphan medicinal product elsewhere for this condition. (europa.eu)
  • Phenylketonuria (PKU) is a genetic disorder characterized by a deficiency in, or problem with the proper activity of, the enzyme phenylalanine hydroxylase (PAH), which is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine . (newworldencyclopedia.org)
  • High frequency of copy number variations and sequence variants at CYP21A2 locus: implication for the genetic diagnosis of 21-hydroxylase deficiency. (cdc.gov)
  • Molecular characterization of Thai patients with phenylalanine hydroxylase deficiency and in vitro functional study of two novel PAH variants. (cdc.gov)
  • A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype, Am. J. Hum. (cytgen.com)
  • Phenylketonuria (PKU), a congenital metabolic disease [ 1 ], is caused by phenylalanine metabolism disorder resulting from phenylalanine hydroxylase deficiency in the liver due to chromosomal gene mutation, which often leads to central nervous system damage [ 2 , 3 ]. (hindawi.com)
  • Phenylalanine hydroxylase deficiency: diagnosis and management guideline. (nih.gov)
  • PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. (wikipedia.org)
  • heterolytic cleavage of the O-O bond to yield the ferryl oxo hydroxylating intermediate Fe(IV)=O attack on Fe(IV)=O to hydroxylate phenylalanine substrate to tyrosine. (wikipedia.org)
  • Although initially an arene oxide or radical intermediate was proposed, analyses of the related tryptophan and tyrosine hydroxylases have suggested that the reaction instead proceeds through a cationic intermediate that requires Fe(IV)=O to be coordinated to a water ligand rather than a hydroxo group. (wikipedia.org)
  • The structure of the N-terminal regulatory domain has also been determined, and together with the solved structure of the homologous tyrosine hydroxylase C-terminal tetramerization domain, a structural model of tetrameric PAH was proposed. (wikipedia.org)
  • The most well-established human function of tetrahydrobiopterin (BH4) is as the cofactor for phenylalanine-4-hydroxylase (PAH), tyrosine-3-hydroxylase, and tryptophan-5-hydroxylase. (medscape.com)
  • The enzyme that converts the essential amino acid phenylalanine to the amino acid tyrosine using tetrahydrobiopterin and molecular oxygen. (blogspot.com)
  • These metabolites are elevated when the conversion of phenylalanine to tyrosine is impaired. (blogspot.com)
  • the pathologic condition of increased excretion of phenylketones in the urine because of impaired conversion of phenylalanine to tyrosine. (blogspot.com)
  • PKU is one of the few genetic diseases that can be controlled by diet, involving low consumption of phenylalanine and a diet high in tyrosine. (newworldencyclopedia.org)
  • The intricate coordination of systems in the human body is seen in the process, catalyzed by enzymes , by which phenylalanine is degraded into tyrosine, which in turn is converted into the vitally important neurotransmitters and hormones dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). (newworldencyclopedia.org)
  • Phenylalanine is an α- amino acid that is found in many proteins (such as hemoglobin ), is essential in the human diet, and normally is readily converted to the amino acid tyrosine in the human body . (newworldencyclopedia.org)
  • L-phenylalanine can be converted into L- tyrosine , another one of the DNA -encoded amino acids. (newworldencyclopedia.org)
  • The enzyme phenylalanine hydroxylase (PAH) is fundamental to the process through conversion of amino acid phenylalanine into the amino acid tyrosine. (newworldencyclopedia.org)
  • If the reaction converting phenylalanine to tyrosine does not take place, because of the lack of PAH or a defect in this enzyme, then phenylalanine accumulates and tyrosine is deficient. (newworldencyclopedia.org)
  • Phenylalanine hydroxylase (PAH) is a member of aromatic amino acid hydroxylase (AAAHs) family, and catalyze phenylalanine (Phe) into tyrosine (Tyr). (kactusbio.com)
  • Phe is one of the essential amino acids in the human body and metabolized via the conversion of coenzyme tetrahydrobiopterin (BH4) into tyrosine (Tyr) under the action of Phe hydroxylase (PAH) [ 6 ]. (hindawi.com)
  • Phenylalanine is normally converted in the human body to tyrosine, another amino acid, by a specific organic catalyst, or enzyme, called phenylalanine hydroxylase. (altouxmal.com)
  • Dysfunction of human phenylalanine hydroxylase (hPAH, EC 1.14.16.1) is the primary cause of phenylketonuria, the most common inborn error of amino acid metabolism. (rcsb.org)
  • In humans, mutations in its encoding gene, PAH, can lead to the metabolic disorder phenylketonuria. (wikipedia.org)
  • Phenylketonuria (PKU) is a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. (genengnews.com)
  • The structural biology of Phenylalanine Hydroxylase, the enzyme that underlies the condition phenylketonuria (PKU) ( recent publication ). (upenn.edu)
  • A long noncoding RNA from humans appeared to help the enzyme phenylalanine hydroxylase work better in a mouse model of phenylketonuria, the disorder characterized by reduced activity of that enzyme. (the-scientist.com)
  • Richard contributed greatly to identification of the genes for phenylketonuria (PKU) and its variants by conceiving, planning and executing myeloma studies, conceiving affinity adsorbents for PAH (phenylalanine hydroxylase, the enzyme deficient in PKU) & DHPR (di-hydro-folate reductase, also involved in PKU), as well as contributing to tests that are now applied worldwide to all newborns being screened for this disease. (humanvariomeproject.org)
  • Phenylketonuria is the inability to metabolize phenylalanine. (newworldencyclopedia.org)
  • Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH). (wichita.edu)
  • Phenylalanine ammonia lyase, enzyme substitution therapy for phenylketonuria, where are we now? (moam.info)
  • Abstract Phenylketonuria (PKU) is an autosomal recessive genetic disorder in which mutations in the phenylalanine-4-hydroxylase (PAH) gene result in an inactive enzyme (PAH, EC 1.14.16.1). (moam.info)
  • Genetic variants of the phenylalanine hydroxylase gene in patients with phenylketonuria in the northeast of Iran. (cdc.gov)
  • replica handbags china Phenylketonuria (PKU), also called phenylpyruvic oligophrenia, hereditary inability of the body to metabolize the amino acid phenylalanine. (altouxmal.com)
  • Now, scientists at the University of Texas MD Anderson Cancer Center have discovered a new factor in regulating phenylalanine metabolism, which will guide researchers in preventing PKU. (genengnews.com)
  • Their findings are published in the journal Science in a paper titled, " A noncoding RNA modulator potentiates phenylalanine metabolism in mice . (genengnews.com)
  • PKU is caused by the defect of phenylalanine hydroxylase activity in children, which causes phenylalanine metabolism disorder, and tetrahydrobiopterin intervention therapy can affect the activity of phenylalanine hydroxylase, increase the decline rate of blood Phe, significantly reduce the level of phenylalanine in children, and promote intellectual recovery. (hindawi.com)
  • 3473611 ). N-Acetyl-L-phenylalanine is a product of enzyme phenylalanine N-acetyltransferase [EC 2.3.1.53] Which is found in the phenylalanine metabolism pathway. (np-mrd.org)
  • He is a pioneer in the field of Mutation Detection, developing methods for the chemical and enzymatic detection of human genetic mutations. (humanvariomeproject.org)
  • Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations, Am. J. Hum. (cytgen.com)
  • PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. (wikipedia.org)
  • What is known about the effectiveness of these treatment and management strategies overall and with respect to variables such as time of initiation of dietary management, level of phenylalanine at various ages, methods for enhancing dietary compliance, duration of dietary management, and dietary regimen for women of childbearing age and other adults? (nih.gov)
  • The eVect is an inability to metabolize phenylalanine (Phe), translating into elevated levels of Phe in the bloodstream (hyperphenylalaninemia). (moam.info)
  • An enzyme needed to metabolize phenylalanine, an amino acid found in most protein-containing foods. (biomarin.com)
  • Phenylalanine hydroxylase from Legionella pneumophila (lpPAH) has a major functional role in the synthesis of the pigment pyomelanin, which is a potential virulence factor. (uit.no)
  • Background: Legionella pneumophila is a pathogenic bacterium that can cause Legionnaires' disease and other non-pneumonic infections in humans. (uib.no)
  • High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. (expasy.org)
  • Tetrahydrobiopterin deficiencies are disorders that affect phenylalanine (Phe) homeostasis, as well as brain biosynthesis of catecholamine, serotonin, and (occasionally) nitric oxide. (medscape.com)
  • 16465618 ). In addition to the NAT enzymes and protein-based acetylation, N-acetylation of free phenylalanine can also occur. (np-mrd.org)
  • In humans, the L-isomer of phenylalanine, which is the only form that is involved in protein synthesis, is one of the 20 standard amino acids common in animal proteins and required for normal functioning in humans. (newworldencyclopedia.org)
  • Scalar light instructions are able to assemble and maintain molecules of amino acids and proteins crucial to human and animal quantum health. (scalarlight.com)
  • The Scalar Light Amino Acid and Protein Program operates twenty-four (24) hours per day seven (7) days per week thereby assuring a constant creation and delivery of amino acids and proteins to the quantum, human body. (scalarlight.com)
  • Amino acids that the human body cannot synthesize (or cannot synthesize in sufficient quantities to meet cellular needs) and must be taken in the diet. (blogspot.com)
  • Those amino acids that are synthesized by the human body in sufficient quantities to meet cellular needs. (blogspot.com)
  • There are 10 such amino acids for which biosynthetic pathways do not exist in cells of the human body. (blogspot.com)
  • N-Acetyl-L-phenylalanine or N-Acetylphenylalanine, belongs to the class of organic compounds known as N-acyl-alpha amino acids. (np-mrd.org)
  • Phenylalanine also is classified as an "essential amino acid" since it cannot be synthesized by the human body from other compounds through chemical reactions and thus has to be taken in with the diet. (newworldencyclopedia.org)
  • Members who choose to subscribe to Human Mutation will receive a substantial discount. (hgvs.org)
  • Following this discovery, Richard's research focus shifted to the biochemical genetics of human disease and he began to focus on human genetic mutation-the damaging of our genetic material that causes inherited disease and cancer. (humanvariomeproject.org)
  • In 1992, Richard Cotton founded the scientific journal Human Mutation, which has since grown to be a top 20 journal in the category of Genetics and Heredity. (humanvariomeproject.org)
  • Human mutation 2020 4 41 (7): 1329-1338. (cdc.gov)
  • Human mutation 2021 7 42 (10): 1229-1238. (cdc.gov)
  • PAH mutation analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus, Nucleic Acids Res. (cytgen.com)
  • This product is for research use only and is not approved for use in humans or in clinical diagnosis. (novusbio.com)
  • N-PAC (AAH64940.1, 1 a.a. - 484 a.a.) full-length human protein. (novusbio.com)
  • In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. (bvsalud.org)
  • Recombinant Human PAH (D415N) Protein is expressed from Baculovirus-Insect Cells with His tag at the N-terminus.It contains Met1-Lys452 (D415N). (kactusbio.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human G Protein Coupled Estrogen Receptor 1 (GPER) in serum, plasma, tissue homogenates and other biological fluids. (allelisakits.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human G Protein Coupled Estrogen Receptor 1 (GPER) in samples from serum, plasma, tissue homogenates and other biological fluids with no significant corss-reactivity with analogues from other species. (allelisakits.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tumor Protein, Translationally Controlled 1 (TPT1) in tissue homogenates, cell lysates, cell culture supernates and other biological fluids. (allelisakits.com)
  • Description: A competitive ELISA for quantitative measurement of Human Translationally controlled tumor protein(TPT1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. (allelisakits.com)
  • Explore the normal functions of human genes and the health implications of genetic changes. (medlineplus.gov)
  • Humans have about 20,000 to 23,000 genes. (msdmanuals.com)
  • Phenylalanine hydroxylase has long been known to be regulated by allosteric factors, but we didn't know what those factors were until now. (genengnews.com)
  • At the time designation, Kuvan (sapropterin) and Palynziq (pegvaliase) were authorised in the EU to treat high blood levels of phenylalanine. (europa.eu)
  • The Andean altiplano has long been a focus of research into high-altitude adaptation for a number of reasons including relative accessibility, the large numbers of altitude-adapted species that thrive there, the presence of large indigenous human populations and the early involvement in the field by such eminent Latin American biologists as Carlos Monge M., his son Carlos Monge C. and Alberto Hurtado. (silverchair.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Cytochrome b (COB) in samples from Tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (antibody-tech.com)
  • This causes phenylalanine to build up in the blood to harmful levels and can lead to brain damage and impair normal development. (europa.eu)
  • This is because laboratory studies showed that a single dose of the medicine is able to lower levels of phenylalanine in the blood and keep levels low for a long time, meaning that patients would not need regular treatment. (europa.eu)
  • Phenylalanine is added to the diet, which is then adjusted according to blood PHE levels. (nih.gov)
  • Women affected by PKU must pay special attention to their diet if they wish to become pregnant, since high levels of phenylalanine in the uterine environment can cause severe malformation and mental retardation in the child. (newworldencyclopedia.org)
  • Penrose [ 5 ] later confirmed that the main contributor to the disease was the excessive levels of phenylalanine (Phe) in the blood, so the disease was named hyperphenylalaninaemia (HPA) and afterwards named PKU. (hindawi.com)
  • Human body needs to control its body fluid levels, in order to function properly. (supreme-essay.com)
  • The screening ciency the Delfia® time-resolved fluores- tests themselves but includes all of the protocol utilized a combination of MS/ cence application (Wallac Oy) was used elements essential for every neonate MS, molecular technologies and bio- to determine levels of phenylalanine to have access to a screening system chemical analysis. (who.int)
  • During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. (wikipedia.org)
  • thus, molecular oxygen is the source of both oxygen atoms used to hydroxylate the pterin ring and phenylalanine. (wikipedia.org)
  • There is a growing appreciation for the role of long noncoding RNAs in a variety of human diseases, but this is the first discovery of any long noncoding RNA involved with PKU," said co-senior author Liuqing Yang, PhD, associate professor of molecular & cellular oncology. (genengnews.com)
  • As the founder and Scientific Director of the Human Variome Project, he has led the world in developing ways to collect, curate, interpret and share information on the genetic changes that underlie both inherited and complex disease. (humanvariomeproject.org)
  • A complex trait is influenced by multiple genetic and environmental factors and, in humans, it is inherently very difficult to determine what proportion of the trait is dictated by an individual's genetic heritage and what proportion develops in response to the environment in which the person is born and raised. (silverchair.com)
  • The human body is complex. (supreme-essay.com)
  • When productive, though, the Fe(IV)=O intermediate is added to phenylalanine in an electrophilic aromatic substitution reaction that reduces iron from the ferryl to the ferrous state. (wikipedia.org)
  • PKU patients respond to treatment with a low-phenylalanine diet, but compliance with the diet is diYcult, therefore the development of alternative treatments is desirable. (moam.info)
  • This is the only known role of PAH in the human body (Krapp and Wilson 2005). (newworldencyclopedia.org)
  • A small structure within a cell that performs a dedicated function, analogous to an organ in the human body. (biomarin.com)
  • The human body is an organism made up of building blocks. (supreme-essay.com)
  • The two thirds of the human body is water. (supreme-essay.com)
  • By working with clinicians, diagnostic labs and national governments to make information on genetic variations and their effect on patients freely and openly available, the Human Variome Project is enabling universal access to knowledge that can be used to prevent, diagnose and treat all human disease. (humanvariomeproject.org)
  • Nearly 20,000 lncRNAs identified in human cells may play some role in cellular activities. (the-scientist.com)