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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] |
Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme, pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Porphobilinogen Synthase
Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme () that in humans is encoded by the ''ALAD'' gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydratase) synthesizes porphobilinogen through the asymmetric condensation of two molecules of aminolevulinic acid. All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, share porphobilinogen as a common precursor. Porphobilinogen synthase is the prototype morpheein. Function It catalyzes the following reaction, the second step of the biosynthesis of porphyrin: :2 5- Aminolevulinic acid \rightleftharpoons porphobilinogen + 2 H2O It therefore catalyzes the condensation of 2 molecules of 5-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). This reaction is the first common step in the biosynthesis of all biological tetrapyrroles. Zinc is essential for enzymatic activity. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C57BL/6
C57BL/6, often referred to as "C57 black 6", "B6", "C57" or "black 6", is a common inbred strain of laboratory mouse. It is the most widely used "genetic background" for genetically modified mice for use as models of human disease. They are the most widely used and best-selling mouse strain due to the availability of congenic strains, easy breeding, and robustness. The median lifespan of C57BL/6 mice is 27–29 months and the maximum lifespan is about 36 months. Origin The inbred strain of C57BL mice was created in 1921 by C. C. Little at the Bussey Institute for Research in Applied Biology. The substrain "6" was the most popular of the surviving substrains. Little's supervisor William E. Castle had obtained the predecessor strain of C57BL/6, "mouse number 57", from Abbie Lathrop who was breeding inbred strains for mammary tumor research in collaboration with Leo Loeb at the time. Appearance and behavior C57BL/6 mice have a dark brown, nearly black coat. They are mor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Knockout Mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. Mice are currently the laboratory animal species most closely related to humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, fo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mass Spectrometry
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used in many different fields and is applied to pure samples as well as complex mixtures. A mass spectrum is a type of plot of the ion signal as a function of the mass-to-charge ratio. These spectra are used to determine the elemental or isotopic signature of a sample, the masses of particles and of molecules, and to elucidate the chemical identity or structure of molecules and other chemical compounds. In a typical MS procedure, a sample, which may be solid, liquid, or gaseous, is ionization, ionized, for example by bombarding it with a Electron ionization, beam of electrons. This may cause some of the sample's molecules to break up into positively charged fragments or simply become positively charged without fragmenting. These ions (fragmen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Newborn Screening
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] |
Guthrie Test
The neonatal heel prick is a blood collection, blood collection procedure done on newborns. It consists of making a pinprick puncture in one heel of the newborn to collect their blood. This Medical procedure, technique is used frequently as the main way to collect blood from neonates. Other techniques include vein, venous or artery, arterial needle sticks, cord blood sampling, or umbilical line collection. This technique is often utilized for the Guthrie test, where it is used to soak the blood into pre-printed collection cards known as Guthrie cards. The classical Guthrie test is named after Robert Guthrie (microbiologist), Robert Guthrie, an American bacteriologist and physician who devised it in 1962. The test has been widely used throughout North America and Europe as one of the core newborn screening tests since the late 1960s. The test was initially a bacterial inhibition assay, but is gradually being replaced in many areas by newer techniques such as tandem mass spectromet ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacological Chaperone
A pharmacological chaperone or pharmacoperone is a drug that acts as a chaperone (protein), protein chaperone. That is, it contains small molecules that enter cells and serve as a molecular scaffolding in order to cause otherwise-protein folding, misfolded mutant proteins to fold and route correctly within the cell. Mutation of proteins often causes molecular misfolding, which results in protein misrouting within the cell. Accordingly, mutant molecules may retain proper function but end up in parts of the cell where the function is inappropriate, or even deleterious, to cell function. Misfolded proteins are usually recognized by the quality-control system of the cell and retained (and often destroyed or recycled) in the endoplasmic reticulum. Pharmacoperones correct the folding of misfolded proteins, allowing them to pass through the cell's quality-control system and become correctly routed. Since mutations often cause disease by causing misfolding and misrouting, pharmacoperones ... [...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 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 phenylalanine concentrations in unaffected persons are about 2-6mg/dl (120–360 μmol/L) phenylalanine concentrations in those with untreated hyperphenylalaninemia can be up to 20 mg/dL (1200 μmol/L). Measurable IQ deficits are often detected as phenylalanine levels approach 10 mg/dL (600 mol/L). Phenylketonuria (PKU)-like symptoms, including more pronounced developmental defects, skin irritation, and vomiting, may appear when phenylalanine levels are near 20 mg/dL (1200 mol/L).Hyperphenylalaninemia is a recessive hereditary metabolic disorder that is caused by the body ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tryptophan Hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction : L-tryptophan + tetrahydrobiopterin + O2 \rightleftharpoons 5-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron. Function It is responsible for addition of the -OH group ( hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin. Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the ''TH'' gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs). Reaction Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the meta position to obt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenylpyruvate
Phenylpyruvic acid is the organic compound with the formula C6H5CH2C(O)CO2H. It is a keto acid. Occurrence and properties The compound exists in equilibrium with its (''E'')- and (''Z'')-enol tautomers. It is a product from the oxidative deamination of phenylalanine. When the activity of the enzyme phenylalanine hydroxylase is reduced, the amino acid phenylalanine accumulates and gets converted into phenylpyruvic acid (phenylpyruvate), which leads to ' Phenylketonuria (PKU)' instead of 'tyrosine' which is the normal product of phenylalanine hydroxylase. Preparation and reactions It can be prepared by many methods. Classically it is produced from aminocinnamic acid derivatives. It has been prepared by condensation of benzaldehyde and glycine derivatives to give phenylazlactone, which is then hydrolyzed with acid- or base-catalysis. It can also be synthesized from benzyl chloride by double carbonylation. Reductive amination of phenylpyruvic acid gives phenylalanine. See a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
