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Pku
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 microcephaly, small head, and low birth weight. Phenylketonuria is an Heredity, inherited genetic disorder. It is caused by mutations in the ''PAH gene, 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 mutat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Newborn Screening Program
Newborn screening (NBS) is a public health program of screening (medicine), screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions early enough to confirm the diagnosis and provide intervention that will alter the clinical course of the disease and prevent or ameliorate the clinical manifestations. NBS started with the discovery that the amino acid disorder phenylketonuria (PKU) could be treated by dietary adjustment, and that early intervention was required for the best outcome. Infants with PKU appear normal at birth, but are unable to metabolize the essential amino acid phenylalanine, resulting in irreversible intellectual disability. In the 1960s, Robert Guthrie (microbiologist), Robert Guthrie developed a simple method using a bacterial inhibition assay that could detect high levels of phenylalanine in blood shortly after a baby was born. Guth ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PAH Gene
Phenylalanine hydroxylase (PAH) () is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. 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. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans, mutations in its encoding gene, ''PAH (gene), PAH'', can lead to the metabolic disorder phenylketonuria. Enzyme mechanism The reaction is thought to proceed through the following steps: # formation of a Fe(II)-O-O-BH4 bridge. # 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. Formation and cleavage of the iron-peroxypterin bridge. Although evidenc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenylalanine Hydroxylase
Phenylalanine hydroxylase (PAH) () is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. 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. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans, mutations in its encoding gene, '' PAH'', can lead to the metabolic disorder phenylketonuria. Enzyme mechanism The reaction is thought to proceed through the following steps: # formation of a Fe(II)-O-O-BH4 bridge. # 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. Formation and cleavage of the iron-peroxypterin bridge. Although evidence strong ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sapropterin Dihydrochloride
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 treatin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ivar Asbjørn Følling
Ivar Asbjørn Følling (23 August 1888 – 24 January 1973) was a Norwegian physician and biochemist. He first described the disease commonly known as Følling's disease or phenylketonuria (PKU). Early life and education He was born on 23 August 1888 at Kvam (in the present-day Steinkjer Municipality in Trøndelag county, Norway). Følling studied chemistry at the Norwegian Institute of Technology in Trondheim and graduated in 1916. He then went to the University of Kristiania (now the University of Oslo), graduating in medicine in 1922. He received his cand.med. in 1929 after doing postgraduate work in Norway and abroad in Denmark, England, Vienna and the U.S. Starting in 1932, Følling occupied a series of medical posts in Oslo, culminating in his being Professor of Biochemistry and Physician-in-Chief at the central laboratory at the Norwegian national research hospital Oslo University Hospital. Følling was a professor of biochemistry at the University of Oslo for more than ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pegvaliase
Pegvaliase, sold under the brand name Palynziq, is a medication used for the treatment of the genetic disease phenylketonuria (PKU). It is a phenylalanine (Phe)‑metabolizing enzyme. Chemically, it is a pegylated derivative of the enzyme phenylalanine ammonia-lyase that metabolizes phenylalanine to reduce its blood levels. The most common adverse events include injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and, diarrhea. It was approved by the US Food and Drug Administration (FDA) for use in the United States in 2018. The FDA considers it to be a first-in-class medication. Medical uses Pegvaliase is indicated to reduce blood Phe concentrations in adults with phenylketonuria who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management. Adverse effects The FD ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Medical Genetics
Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics. In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). ''Genetic medicine'' is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, 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 chemical polarity, nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The chirality (chemistry)#Naming conventions, 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 biological pigment melanin. It is Genetic code, encoded by the messenger RNA 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 as it is a direct precursor to the neuromodulation, neuromodulator phe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inborn Error Of Metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrate (biochemistry), substrates) into others (Product (chemistry), products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or due to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are often referred to as congenital metabolic diseases or inherited metabolic disorders. Another term used to describe these disorders is "enzymopathies". This term was created following the study of Biochemical Processes, biodynamic enzymology, a science based on the study of the enzymes and their products. Finally, ''inborn errors of metabolism'' were studied for the first time by British physician Archibald Garrod (1857–1936), in 1908. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
