Biomaterial Database

Peptidylglycine alpha-amidating mono-oxygenase: neuropeptide amidation as a target for drug design. 1998

F N Bolkenius, and A J Ganzhorn

Synthélabo Biomoléculaire 16, Strasbourg, France.

1. Peptidylglycine alpha-amidating mono-oxygenase (PAM) is a bifunctional key enzyme in the bioactivation of neuropeptides. Its biosynthesis, distribution, functional role, and pharmacological manipulation are discussed. 2. PAM biosynthesis from a single gene precursor is characterized by alternative splicing and endoproteolytic events, which control intracellular transport, targeting, and enzyme activity. 3. The enzyme is mainly stored in secretory vesicles of many neuronal and endocrine cells with high abundance in the pituitary gland. Its functional role has been studied using enzyme inhibitors. Thus selective, peripheral PAM inhibition reduces substance P along with an anti-inflammatory action. 4. PAM-related pathologies are characterized by an increased relative abundance of alpha-amidated neuropeptides. To attenuate such hormone overproduction, novel, specific, and disease-targeted PAM inhibitors may be developed based on enzyme polymorphism.

UI	MeSH Term	Description	Entries
D009097	Multienzyme Complexes	Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.	Complexes, Multienzyme
D009479	Neuropeptides	Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.	Neuropeptide
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs