-
Cold Spring Harbor Protocols Aug 2020Several types of alkaline phosphatases (or alkaline phosphomonoesterase) are commonly used in molecular cloning, including bacterial alkaline phosphatase (BAP) and calf...
Several types of alkaline phosphatases (or alkaline phosphomonoesterase) are commonly used in molecular cloning, including bacterial alkaline phosphatase (BAP) and calf intestinal alkaline phosphatase (CIP, CIAP, or CAP). Similar enzymes isolated from more esoteric cold-blooded organisms (e.g., SAP from shrimp) have become available in recent years and have the advantage of being easier to inactivate than BAP or CIP at the end of dephosphorylation reactions. The uses and properties of these enzymes are introduced here.
Topics: Alkaline Phosphatase; Animals; Bacteria; Cattle; Decapoda; Humans; Phosphorylation
PubMed: 32747588
DOI: 10.1101/pdb.top100768 -
Gene Sep 2020Alkaline 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... (Review)
Review
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 outermembrane of hypertrophic osteoblasts and chondrocytes. The expansion of hydroxyapatite formsinto 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.
Topics: Alkaline Phosphatase; Animals; Calcification, Physiologic; Humans; Hypophosphatasia; Isoenzymes
PubMed: 32522695
DOI: 10.1016/j.gene.2020.144855 -
Journal of Bone and Mineral Research :... Feb 2018Alkaline phosphatase can be considered "our favorite enzyme" for reasons apparent to those who diagnose and treat metabolic bone diseases or who study skeletal biology....
Alkaline phosphatase can be considered "our favorite enzyme" for reasons apparent to those who diagnose and treat metabolic bone diseases or who study skeletal biology. Few might know, however, that alkaline phosphatase likely represents the most frequently assayed enzyme in all of medicine. Elevated activity in the circulation is universally recognized as a marker for skeletal or hepatobiliary disease. Nevertheless, the assay conditions in many ways are nonphysiological. The term alkaline phosphatase emerged when it became necessary to distinguish "bone phosphatase" from the phosphatase in the prostate that features an acidic pH optimum. Beginning in 1948, studies of the inborn-error-of-metabolism hypophosphatasia would identify the natural substrates and establish the physiological role of alkaline phosphatase, including in biomineralization. Here, we recount the discovery in 1923 and then eventual naming of this enzyme that remains paramount in our field. © 2017 American Society for Bone and Mineral Research.
Topics: Alkaline Phosphatase; Enzyme Assays; History, 20th Century; Humans; Terminology as Topic
PubMed: 28727174
DOI: 10.1002/jbmr.3225 -
Gastroenterology Mar 1972
Review
Topics: Alkaline Phosphatase; Cells; Electrophoresis; Humans; Immunoassay; Isoenzymes; Liver; Organ Specificity
PubMed: 4551808
DOI: No ID Found -
Nutrition Reviews Oct 2019In recent years, much new data on intestinal alkaline phosphatase (IAP) have been published, and major breakthroughs have been disclosed. The aim of the present review... (Review)
Review
In recent years, much new data on intestinal alkaline phosphatase (IAP) have been published, and major breakthroughs have been disclosed. The aim of the present review is to critically analyze the publications released over the last 5 years. These breakthroughs include, for example, the direct implication of IAP in intestinal tight junction integrity and barrier function maintenance; chronic intestinal challenge with low concentrations of Salmonella generating long-lasting depletion of IAP and increased susceptibility to inflammation; the suggestion that genetic mutations in the IAP gene in humans contribute to some forms of chronic inflammatory diseases and loss of functional IAP along the gut and in stools; stool IAP as an early biomarker of incipient diabetes in humans; and omega-3 fatty acids as direct inducers of IAP in intestinal tissue. Many recent papers have also explored the prophylactic and therapeutic potential of IAP and other alkaline phosphatase (AP) isoforms in various experimental settings and diseases. Remarkably, nearly all data confirm the potent anti-inflammatory properties of (I)AP and the negative consequences of its inhibition on health. A simplified model of the body AP system integrating the IAP compartment is provided. Finally, the list of nutrients and food components stimulating IAP has continued to grow, thus emphasizing nutrition as a potent lever for limiting inflammation.
Topics: Alkaline Phosphatase; Animals; Gastrointestinal Microbiome; Humans; Inflammation; Intestines; Nutritional Physiological Phenomena
PubMed: 31086953
DOI: 10.1093/nutrit/nuz015 -
Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target.Current Cardiology Reviews 2019Vascular calcification is a pathologic phenomenon consisting of calcium phosphate crystal deposition in the vascular walls. Vascular calcification has been found to be a... (Review)
Review
Vascular calcification is a pathologic phenomenon consisting of calcium phosphate crystal deposition in the vascular walls. Vascular calcification has been found to be a risk factor for cardiovascular diseases, due to its correlation with cardiovascular events and mortality, and it has been associated with aging, diabetes, and chronic kidney disease. Studies of vascular calcification have focused on phosphate homeostasis, primarily on the important role of hyperphosphatemia. Moreover, vascular calcification has been associated with loss of plasma pyrophosphate, one of the main inhibitors of calcification, thus indicating the importance of the phosphate/pyrophosphate ratio. Extracellular pyrophosphate can be synthesized from extracellular ATP by ecto-nucleotide pyrophosphatase/ phosphodiesterase, whereas pyrophosphate is hydrolyzed to phosphate by tissuenonspecific alkaline phosphatase, contributing to the formation of hydroxyapatite crystals. Over the last decade, vascular calcification has been the subject of numerous reviews and studies, which have revealed new agents and activities that may aid in explaining the complex physiology of this condition. This review summarizes current knowledge about alkaline phosphatase and its role in the process of vascular calcification as a key regulator of the phosphate/pyrophosphate ratio.
Topics: Alkaline Phosphatase; Humans; Vascular Calcification
PubMed: 30381085
DOI: 10.2174/1573403X14666181031141226 -
Chemico-biological Interactions Jan 2015Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is... (Review)
Review
Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases.
Topics: Alkaline Phosphatase; Alzheimer Disease; Animals; Humans; Inflammation; Organ Specificity; Protein Transport
PubMed: 25500268
DOI: 10.1016/j.cbi.2014.12.006 -
Sub-cellular Biochemistry 2015
Topics: Alkaline Phosphatase; Animals; Biomarkers; Child; Humans; Infant; Mice; Models, Animal; Rats
PubMed: 26410897
DOI: No ID Found -
International Journal of Molecular... May 2021Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP's... (Review)
Review
Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP's function is well-recognized from earlier studies establishing its important role in bone mineralization. TNAP is also highly expressed in cerebral microvessels; however, its function in brain cerebral microvessels is poorly understood. In recent years, few studies have begun to delineate a role for TNAP in brain microvascular endothelial cells (BMECs)-a key component of cerebral microvessels. This review summarizes important information on the role of BMEC TNAP, and its implication in health and disease. Furthermore, we discuss current models and tools that may assist researchers in elucidating the function of TNAP in BMECs.
Topics: Alkaline Phosphatase; Animals; Brain; Central Nervous System; Endothelial Cells; Humans; Microvessels
PubMed: 34067629
DOI: 10.3390/ijms22105257 -
Clinical Chemistry Dec 1992Gene cloning and site-directed mutagenesis have had a profound effect on alkaline phosphatase research. Four distinct structural genes encoding placental, intestinal,... (Review)
Review
Gene cloning and site-directed mutagenesis have had a profound effect on alkaline phosphatase research. Four distinct structural genes encoding placental, intestinal, and tissue-nonspecific isoenzymes have been cloned, sequenced, and mapped to human chromosomes. Differences in properties between the respective gene products are due to variations in primary structure involving only one, or a few, key amino acid residues. Recognition that alkaline phosphatase belongs to the category of molecules that are localized to cell membranes through a COOH-terminal glycan-phosphatidylinositol anchor provides a basis for understanding the generation of isoforms observed in plasma in disease. Isoforms produced by differential cleavage or preservation of the glycan-phosphatidylinositol anchor may offer new correlations with disease that are of diagnostic value. However, a more important contribution of alkaline phosphatase research to clinical chemistry may prove to be an increased understanding of disease processes at the molecular level.
Topics: Alkaline Phosphatase; Cell Membrane; Fetus; Gene Expression; Humans; Isoenzymes; Molecular Structure
PubMed: 1458591
DOI: No ID Found