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PDE4A
cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the ''PDE4A'' gene. Function The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, cyclic adenosine monophosphate, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Recently, it has been shown through the use of PDE4A knock out mice that PDE4A may play a role in the regulation of anxiety and emotional memory. Clinical significance PDE4A inhibition is a target of a number of drugs including: * rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7 * roflumilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6 References ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclic Nucleotide Phosphodiesterase
3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate: :nucleoside 3′,5′-cyclic phosphate + H2O = nucleoside 5′-phosphate They thus control the cellular levels of the cyclic second messengers and the rates of their degradation. Some examples of nucleoside 3′,5′-cyclic phosphate include: * 3′,5′-cyclic AMP *3′,5′-cyclic dAMP *3′,5′-cyclic IMP * 3′,5′-cyclic GMP *3′,5′-cyclic CMP There are 11 distinct phosphodiesterase families (PDE1–PDE11) with a variety in isoforms and splicing having unique three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities. Nomenclature The systematic name for this enzyme is 3′,5′-cyclic-nucleotide 5'-nucleotidohydrolase. Other names in use include cyclic 3′,5′-mononucleoti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE4
At least four types of the enzyme phosphodiesterase 4 (PDE4) are known: * PDE4A * PDE4B * PDE4C * PDE4D See also * 3',5'-cyclic-AMP phosphodiesterase * Phosphodiesterase (PDE) * PDE4 inhibitor A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitor ... {{chemistry index Molecular biology ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the 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 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 are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the react ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydrolyzes
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis is the cleavage of biomolecules where a water molecule is consumed to effect the separation of a larger molecule into component parts. When a carbohydrate is broken into its component sugar molecules by hydrolysis (e.g., sucrose being broken down into glucose and fructose), this is recognized as saccharification. Hydrolysis reactions can be the reverse of a condensation reaction in which two molecules join into a larger one and eject a water molecule. Thus hydrolysis adds water to break down, whereas condensation builds up by removing water. Types Usually hydrolysis is a chemical process in which a molecule of water is added to a substance. Sometimes this addition causes both the substance and water molecule to split into two parts. I ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclic Adenosine Monophosphate
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. History Earl Sutherland of Vanderbilt University won a Nobel Prize in Physiology or Medicine in 1971 "for his discoveries concerning the mechanisms of the action of hormones", especially epinephrine, via second messengers (such as cyclic adenosine monophosphate, cyclic AMP). Synthesis Cyclic AMP is synthesized from ATP by adenylate cyclase located on the inner side of the plasma membrane and anchored at various locations in the interior of the cell. Adenylate cyclase is ''activated'' by a range of signaling molecules through the activation of adenylate cyclase stimulatory G ( Gs)-protein-coupled receptors. Adenylate cyclase is ''inhibited'' by agonists of adenyl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rolipram
Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. It served as a prototype molecule for several companies' drug discovery and development efforts.McKenna, JM and Muller, GW. Medicinal Chemistry of PDE4 Inhibitors. Chapter 33 in Cyclic Nucleotide Phosphodiesterases in Health and Disease, Eds Joseph A. Beavo et al. CRC Press, Dec 5, 2006 Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects. Rolipram has several activities that make it a continuing focus for research. The etiology of many neurodegenerative diseases involves misfolded and clumped proteins which accumulate in the brain. Cells have a mechanism to dispose of such proteins called the proteasome. However, in Alzheimer's disease and some other conditions t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cilomilast
Cilomilast (INN, codenamed SB-207,499, proposed trade name Ariflo) is a drug which was developed for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). It is orally active and acts as a selective phosphodiesterase-4 inhibitor. Phosphodiesterase (PDE) inhibitors, such as theophylline, have been used to treat COPD for centuries; however, the clinical benefits of these agents have never been shown to outweigh the risks of their numerous adverse effects. Four clinical trials were identified evaluating the efficacy of cilomilast, the usual randomized, double-blind, and placebo-controlled protocols were used. It showed reasonable efficacy for treating COPD, but side effects were problematic and it is unclear whether cilomalast will be marketed, or merely used in the development of newer drugs. Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction, mucus hypersecretion, and airw ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
