Mammilian Alkaline Phosphatases

INTRODUCTION AND SCOPE
GENOMIC ORGANIZATION AND COMPLEXITY
Human APs genes
Mouse AP genes
AP genes in other species
DEVELOPMENTAL EXPRESSION
During embryogenesis
In postnatal and adult life
PROTEIN STRUCTURE
3D structure
Functional domains and mutagenesis
Epitope maps
ENZYME KINETICS
Allosteric behavior
Uncompetitive inhibition mechanism
Substrate specificities
HUMAN AP DEFICINCIES - HYPOPHOSPHATASIA
KNOCKOUT MOUSE MODELS
TNAP deficiency
EAP deficiency
IAP deficiency
IN VIVO FUNCTIONS
In vivo substrates
Metabolic pathways affected by AP deficiencies
Role in bone mineralization
Other organs
Non-catalytic functions
APS AS MARKERS OF DISEASE
Bone and liver disease
Cancer
APS AS THERAPEUTIC MOLECULES
In the treatment of bone disorders
In cancer treatments
Other diseases
AP USES IN BIOTECHNOLOGY
As molecular biology reagents
As diagnostic reagents
As markers in vivo
METHODOLOGIES
Specific detection and quantification by RT-PCR
Histochemical and immunohistochemical detection

José Luis Millán received his early training in Clinical Chemistry at the University of Buenos Aires, Argentina and received pre-doctoral training at the La Jolla Cancer Research Foundation (the predecessor of the Burnham Institute) from 1977-1980. He completed his Ph.D. studies at the University of Umeå, Sweden in 1983. After a period of postdoctoral training at the La Jolla Cancer Research Foundation he was appointed to the staff in 1986. He was promoted to Associate Professor in 1989 and to Professor in 1994 at that Institution. He also held the Chair of Medical Genetics at the Department of Medical Biosciences, School of Medicine, Umeå University, Umeå, Sweden from 1995 to 2000. Dr. Millán is currently Professor at The Burnham Institute and he maintains adjunct affiliations with Umeå University and the Royal Academy of Medicine and Surgery, Murcia, Spain. Professor Millán has dedicated most of his scientific carrier to the understanding of the structure and biological functions of alkaline phosphatases during development and the significance of their re-expression in malignancy. This book highlights and discusses the major advances made in this field in the last 25 years.