Alkaline phosphatase: Structure, expression and its function in bone mineralization

Highlights

• Bone mineralization is an essential process of life.

• ALP is highly expressed in the cells of mineralized tissue.

• TNAP hydrolyzes pyrophosphate and supplies inorganic phosphate.

Abstract

Alkaline phosphatase (ALP) is highly expressed in the cells of mineralized tissue and plays a critical function in the formation of hard tissue. The existing status of this critical enzyme should be reviewed periodically. ALP increases inorganic phosphate local rates and facilitates mineralization as well as reduces the extracellular pyrophosphate concentration, an inhibitor of mineral formation. Mineralization is the production, inside matrix vesicles, of hydroxyapatite crystals that bud from the outer membrane of hypertrophic osteoblasts and chondrocytes. The expansion of hydroxyapatite forms into the extracellular matrix and its accumulation between collagen fibrils is observed. Among various isoforms, the tissue-nonspecific isozyme of ALP (TNAP) is strongly expressed in bone, liver and kidney and plays a key function in the calcification of bones. TNAP hydrolyzes pyrophosphate and supplies inorganic phosphate to enhance mineralization. The biochemical substrates of TNAP are believed to be inorganic pyrophosphate and pyridoxal phosphate. These substrates concentrate in TNAP deficient condition which results in hypophosphatasia. The increased level of ALP expression and development in this environment would undoubtedly provide new and essential information about the fundamental molecular mechanisms of bone formation, offer therapeutic possibilities for the management of bone-related diseases.

Introduction

The extracellular mineralized matrix is a special characteristic of the vertebrate skeletal system. Mineralized tissue functions are not restricted to maintaining the body mass, preserving the internal soft tissues, or even promoting physical movement and mastication; they often act as a conveniently usable source for important minerals that are necessary for several physiological processes. The accumulated minerals are made of calcium phosphate, hydroxyapatite, which is contained in the extracellular matrix. Biochemical mineralization happens in hard tissues such as bone and cartilage, where many tissue-specific cells are involved in this mineralization process. Within bone, osteoblasts that are wrapping the osteoid are accountable for hydroxyapatite production (Murshed, 2018, Karpen, 2018). The reduction in bone density contributing to osteoporosis is attributed to a pathological mineralization deficiency (Ensrud and Crandall, 2017).

Alkaline phosphatase (ALP) [phosphate-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] enzyme is encoded by distinct genes as many tissue-specific isozymes. It is found in several organisms (bacteria, plants, and animals) and active in catalyzing phosphomonoester hydrolysis, R-O-PO3, with no respect for category 'R' identification. The catalytic process includes the creation at the active site of serine phosphate that interacts with water at high pH to liberate inorganic phosphate from the enzyme (Holtz and Kantrowitz, 1999, Golub and Boesze-Battaglia, 2007). As the organic alcohol activates the enzyme-bound inorganic phosphate and is phosphorylated, a transphosphorylation reaction occurs in the existence of elevated concentrations of organic alcohol (Han and Coleman, 1995). For vertebrates, the enzyme is an ectoenzyme that is bound covalently to the outer side of cell membrane by a phosphatidyl inositol glycophospholipid anchor connected to the enzyme's C-terminus (Han and Coleman, 1995, López-Delgado et al., 2018). Human beings have four ALP genes referring to the gene components of the intestinal, placental, placental and liver/bone/kidney (nonspecific tissue; TNAP) (Siller and Whyte, 2018). Throughout the various species and tissues where it exists, ALP has several specific roles, although the aim of this analysis is to understand the role of ALP in bone mineralization.