05260nam 2200613Ia 450 991014396210332120170925054200.01-280-72272-X97866107227233-527-60806-03-527-60747-1(CKB)1000000000375910(EBL)482182(OCoLC)77733698(SSID)ssj0000196333(PQKBManifestationID)11196560(PQKBTitleCode)TC0000196333(PQKBWorkID)10142806(PQKB)11722673(MiAaPQ)EBC482182(EXLCZ)99100000000037591020050504d2006 uy 0engur|n|---|||||txtccrMammalian alkaline phosphatases[electronic resource] from biology to applications in medicine and biotechnology /José Luis MillánWeinheim ;Chichester Wiley-VCHc20061 online resource (340 p.)Description based upon print version of record.3-527-31079-7 Includes bibliographical references and index.Mammalian Alkaline Phosphatases; Contents; Preface; Abbreviations; Glossary; Introduction; Part I Gene and Protein Structure; 1 Gene Structure; 1.1 Genomic Organization and Complexity; 1.2 Restriction Fragment Length Polymorphisms; 2 Developmental Expression; 2.1 The TNAP Gene; 2.2 The TSAP Genes; 3 Gene Regulation; 3.1 The TNAP Gene; 3.2 The TSAP Genes; 4 Protein Structure and Functional Domains; 4.1 The Three-dimensional Structure of PLAP; 4.1.1 Overview of the Structure; 4.1.2 The Active Site; 4.1.3 The Calcium Site; 4.1.4 The Disulfide Bonds; 4.1.5 The N-terminal Arm4.1.6 The Crown Domain4.1.7 The Monomer-Monomer Interface; 4.1.8 The Noncatalytic Peripheral Binding Site; 4.2 Genetic Polymorphism and Protein Variability; 4.3 Post-translational Modifications; 4.3.1 Glycosylation Sites; 4.3.2 Ectoplasmic Localization of APs via a GPI Anchor; 4.3.3 Nonenzymatic Glycation of APs; 4.3.4 Quaternary Structure of APs; 4.3.5 Subcellular Localization of APs; 5 Enzymatic Properties; 5.1 Catalytic Inhibition; 5.1.1 Competitive and Noncompetitive Inhibitors of APs; 5.1.2 Uncompetitive Inhibition; 5.1.2.1 Mechanism of Inhibition in PLAP/GCAP5.1.2.2 Inhibitor Binding in TNAP5.2 Allosteric Behavior; 5.3 Catalytic Efficiency of Mammalian APs; 5.4 Substrate Specificities; 5.5 APs as Members of a Superfamily of Enzymes; 6 Epitope Maps; 6.1 Epitopes in PLAP and GCAP; 6.2 Epitopes in IAP; 6.3 Discrimination Between Bone and Liver TNAP; Part II In Vivo Functions; 7 The In Vivo Role of TNAP; 7.1 Function of TNAP in Bone; 7.1.1 Hypophosphatasia; 7.1.2 Hypophosphatasia Mutations; 7.1.3 Variable Penetrance and Expressivity; 7.2 Role of TNAP in Nonskeletal Tissues; 7.3 Proposed Biological Functions of TSAPs; 7.3.1 Proposed Functions of IAP7.3.2 Putative Functions of GCAP and PLAP8 Knockout Mouse Models; 8.1 Phenotypic Abnormalities in Akp2(-/-) mice; 8.1.1 Developmental and Skeletal Defects; 8.1.2 Dental Abnormalities in Akp2(-/-) Mice; 8.1.3 Deficient Mineralization by Akp2(-/-) Osteoblasts In Vitro; 8.1.4 Metabolic Pathways Affected in Akp2(-/-) Mice; 8.1.4.1 Neuro-physiological Abnormalities; 8.1.4.2 The Function of TNAP in Bone Mineralization; 8.1.4.3 Co-expression of TNAP and Fibrillar Collagens Restricts Calcification to Skeletal Tissues; 8.1.4.4 Other Organs Affected in Akp2(-/-) Mice8.2 Phenotypic Abnormalities in Akp3(-/-) Mice8.3 Phenotypic Abnormalities in Akp5(-/-) Mice; Part III AP Expression in Health and Disease; 9 APs as Physiological and Disease Markers; 9.1 Clinical Usefulness of TNAP; 9.1.1 TNAP as a Marker of Bone Formation; 9.1.2 TNAP and Bone Cancer or Bone Metastasis; 9.1.3 TNAP Expression in Cholestasis; 9.1.4 TNAP in Other Conditions; 9.2 Clinical Usefulness of PLAP in Normal and Complicated Pregnancies; 9.3 IAP Expression in Relation to ABO Status, Fat Feeding and Other Pathologies; 9.4 Complexes of APs and Immunoglobulins; 9.5 Hyperphosphatasia10 Neoplastic Expression of PLAP, GCAP, IAP (Regan, Nagao, Kasahara) and TNAP IsozymesA review and discussion of new knowledge on the structure and function of mammalian alkaline phosphatases (APs) gained over the last 25 years. It covers:* The structure, regulation and expression of the AP genes* The three-dimensional structure of APs and mutagenesis work that further defined the structural/functional domains of the isozymes* The phenotypic abnormalities of the different AP knockout mice* Our current understanding of the in vivo role of the AP isozymes.The book also describes the possible use of APs as therapeutic agents and therapeutic targets and Alkaline phosphataseHydrolasesElectronic books.Alkaline phosphatase.Hydrolases.572.7553Millán José Luis958179MiAaPQMiAaPQMiAaPQBOOK9910143962103321Mammalian alkaline phosphatases2170848UNINA