The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization

Abstract

Tissue-nonspecific alkaline phosphatase (TNAP) is a key enzyme responsible for skeletal tissue mineralization. It is involved in the dephosphorylation of various physiological substrates, and has vital physiological functions, including extra-skeletal functions, such as neuronal development, detoxification of lipopolysaccharide (LPS), an anti-inflammatory role, bile pH regulation, and the maintenance of the blood brain barrier (BBB). TNAP is also implicated in ectopic pathological calcification of soft tissues, especially the vasculature. Although it is the crucial enzyme in mineralization of skeletal and dental tissues, it is a logical clinical target to attenuate vascular calcification. Various tools and studies have been developed to inhibit its activity to arrest soft tissue mineralization. However, we should not neglect its other physiological functions prior to therapies targeting TNAP. Therefore, a better understanding into the mechanisms mediated by TNAP is needed for minimizing off targeted effects and aid in the betterment of various pathological scenarios. In this review, we have discussed the mechanism of mineralization and functions of TNAP beyond its primary role of hard tissue mineralization.

Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease

“…ALP can detoxify bacterial toxins and pro-inflammatory mediators, e.g., adenosine-tri-phosphate, through the dephosphorylation of various compounds. In some animal models of sepsis, ALP has been shown to improve survival rates by reducing inflammation and organ dysfunction [ 48 , 49 , 50 , 51 ]. Clinical studies of different intravenous ALP compounds in sepsis have produced promising renoprotective results.…”

Evaluation of Diagnostic Role of Alkaline Phosphatase in the Patients of Cerebral Stroke

“…23,26 Furthermore, TNAP plays a crucial role in neurotransmitter synthesis and spinal cord myelination. 13,14 30 , showed that ALP levels were significantly altered in stroke patients who underwent cardiac bypass surgery as a result of stroke.…”

“…Under the influence of TNAP, different neurotransmitters are synthesized and regulated. 13,14 In different regions of the world, researchers are investigating the levels of ALP and specific TNAP in brain tissues, cerebrospinal fluid samples, and blood samples to determine different variations in TNAP levels in animal and human models. In the brain, ALP is also involved in phosphorylation.…”

Diet supplementation of organic zinc positively affects growth, antioxidant capacity, immune response and lipid metabolism in juvenile largemouth bass, Micropterus salmoides

“…ALP, a type of metalloenzyme, requires Zn 2+ and Mg 2+ to coordinate with specific amino acid residues. It shows anti-inflammatory activity partly by mediating the detoxification of lipopolysaccharide (LPS) through dephosphorylation (1,52) . ACP also targets the phosphate bonds of external entities for conducting hydrolysis and advance their degradation (51,53) .…”