Alkaline Phosphatases

Abstract

This chapter focuses on the structure and function of tissue nonspecific AP (TNAP), making reference to these new studies. It mentions studies on other AP isozymes when there is paucity of data for TNAP or to exemplify structural features relevant to TNAP activity and function. The alkaline phosphatase isozyme expressed in bone is one of the several members of the mammalian AP gene family. In humans, four genes traditionally named after the tissues where they are predominantly expressed, although the gene nomenclature is now gaining wider use, encode APs. The tissue nonspecific AP (TNAP) gene (ALPL), located on chromosome 1, is expressed at its highest levels in liver, bone, kidney, in the placenta during the 1st trimester of pregnancy, and at lower levels in numerous other tissues. The other three isozymes, that is, placental (PLAP), placental-like or germ cell (GCAP), and intestinal AP (IAP), show a much more restricted tissue expression; hence, the general term tissue specific APs. These isozymes are encoded by three genes clustered on human chromosome 2, bands q34-q37, and are closely related to one another, showing 90% and 87% identical nucleotide and amino acid sequences, respectively. The orthologos TNAP gene in mice is called Akp2 and is located on mouse chromosome 4. The mouse Akp3 gene encodes the IAP isozyme, and the mouse Akp5 gene encodes the embryonic AP (EAP) isozyme that appears to be related to both the human PLAP and GCAP isozymes. © 2006 Elsevier Inc. All rights reserved.