ReviewAlkaline phosphatase: Structure, expression and its function in bone mineralization
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.
Section snippets
Alkaline phosphatase structure
ALP is a metalloenzyme composed of a number of isoenzymes. Each isoenzymes are membrane attached glycoprotein which is encoded by specific loci genes and are believed to be evolved from a common ancestral gene (Golub and Boesze-Battaglia, 2007). 3 ALP genes are located at chromosome 2 and the fourth one that is L/B/K ALP resides at chromosome 1 as shown in Fig. 1. The nomenclature of these genes is based on the tissue where they are highly expressed and the detail has been tabulated in Table 1.
Alkaline phosphatase expression
The review on gene expression during osteoblastic differentiation and growth plate calcification offers a path to understanding the function of ALP in mineralization. ALP is produced early in growth and is easily found on the surface of the cell and in matrix vesicles of all tissues, bones and calcifying cartilages (Siller and Whyte, 2018). Subsequently, whereas certain genes are upregulated (e.g. osteocalcin), ALP expression reduces. In the initial stages of this process, ALP will obviously
Signaling mechanism in bone cell mineralization
ALP is one of the first functioning genes in the calcification mechanism. At least one of its functions in the mineralization cycle is also expected to take place at an early point. The matrix vesicles are extracelular vesicles of 50–200 nm of diameter invested in membranes, shaped by the polarized budding of chondrocytes and osteoblasts on their surface membrane. This function may require large amounts of intracellular calcium and extracellular phosphate. The lipid content varies from the
ALP initiation of calcium deposition in bone cells
ALP is an echoenzyme hydrolyzing the ester of monophosphate at elevated pH (8–10). Human ALP is categorized into four groups, depending on where they are predominantly expressed, as seen in Table 1. Tissue-nonspecific alkaline phosphatase (TNAP) is found in hypertrophic chondrocytes and osteoblasts cell membranes and often concentrates in those cells on the membranes of matrix vesicles. The biochemical substrates of TNAP shall be assumed to be pyridoxal 5′-phosphate (PLP) (Whyte et al., 1995).
ALP deficiency: Hypophosphatasia
ALPL mutations contribute to defects in TNAP function and, as such, extracellular aggregation of PPI, a normal TNAP substrate and a potent inhibitor of mineralization, are the consequence of hypophosphatasia. Hypophosphatasia also includes rickets, osteomalacia and tooth sludge. Enzyme substitution with minerally-target TNAP from birth avoided extreme hypophosphatasia disease in TNAP−/− knockout mice and then proved that babies and young children with life-threatening hypophosphatasia disease was
Conclusion
Bone mineralization is an essential process of life. Understanding of the underlying mineralization processes is important not only in physiological growth, but also to manage mineralization with deficiency. The recent problem in age related bone mineralization is an alert to the researchers to give more attention on development of prevention method in mineralization deficient and disease related to calcification.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This work was supported by Department of Science and Technology, INSPIRE Faculty Program, Government of India for the research grant to S. Vimalraj (grant no. DST/INSPIRE/04/2017/002913).
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