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PDE4A
cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the ''PDE4A'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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: protei .... Function The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, 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 i ... [...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: * PDE, * cyclic 3′,5′-m ... [...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 inhibit ... {{chemistry index Molecular biology ... [...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] |
Gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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 non-coding genes. During gene expression (the synthesis of Gene product, RNA or protein from a gene), DNA is first transcription (biology), copied into RNA. RNA can be non-coding RNA, directly functional or be the intermediate protein biosynthesis, template for the synthesis of a protein. The transmission of genes to an organism's offspring, is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype, that is specific to every given individual, within the gene pool of the population (biology), population of a given species. The genotype, along with environmental and developmental factors, ultimately determines the phenotype ... [...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 reaction, substitution, elimination reaction, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis is the cleavage of Biomolecule, 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 su ... [...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, or cellular signal occurring within cells, that is 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 The synthesis of cAMP is stimulated by trophic hormones that bind to receptors on the cell surface. cAMP levels reach maximal levels within minutes and decrease gradually over an hour in cultured cells. Cyclic AMP is synthesized from ATP by adenylate cyclase located on the inner side of the plasma membrane and anchored at v ... [...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. 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 the activity of these proteasomes is impaired leading to a buildup of toxic aggregates. Research in mice suggests that rolipram has the ability to ramp up the activity of proteasomes and reduce th ... [...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 cilomilast 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 air ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Roflumilast
Roflumilast, sold under the brand name Daxas among others, is a medication used for the treatment of chronic obstructive pulmonary disease, plaque psoriasis, seborrheic dermatitis, and atopic dermatitis. It acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects. It was approved for medical use in the European Union in 2010, in the United States in 2011, and in Canada in 2017. It is available as a generic medication. Medical uses Roflumilast is indicated for the treatment of severe chronic obstructive pulmonary disease (COPD), plaque psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ..., seborrheic dermatitis, and atopic dermatitis, It is used in the prevention of exacerbations (lung attacks) in severe chron ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tofisopam
Tofisopam (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries. Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines (which are generally 1,4- or 1,5-substituted) however, tofisopam does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines (such as diazepam) and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin. Tofisopam is indicated for the treatment of anxiety and alcohol withdrawal, and is prescribed in a dosage of 50–300 mg per day divided into three doses. Peak plasma levels are attained two hours after an oral dose. Tofisopam is not reported as causing dependence to the same extent as other benzodiazepines, but is still recommended to be prescribed for a maximum of 12 weeks. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphodiesterase Inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, with those in the heart and lungs being some of the first to find therapeutic use. History The different forms or subtypes of phosphodiesterase were initially isolated from rat brains in the early 1970s and were soon afterward shown to be selectively inhibited in the brain and in other tissues by a variety of drugs. The potential for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait. This prediction meanwhile has proved to be true in a variety of fields. Classification Nonselective PDE inhibitors Methylated ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphodiesterase 3
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications. Function PDE3 enzymes are involved in regulation of cardiac and vascular smooth muscle contractility. Molecules that inhibit PDE3 were originally investigated for the treatment of heart failure, but, because of unwanted arrhythmic side-effects, they are not studied for that indication any longer. Nonetheless, the PDE3 inhibitor milrinone is approved for use in heart failure in intravenous form. Both PDE3A and PDE3B are expressed in va ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
