Acid Phosphatase Tartrate-Resistant

Kim MS, Day CJ, Selinger Cl, Magno CL, Stephens SR, Morrison NA. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATcl, and calcitonin receptor-positive but require receptor activator of NFkap-paB ligand for bone resorption. J Biol Chem 2006 281(2) 1274-1285. 

Moreover, as expected disruption of genes coding for enzymes critical to the function of osteoclast such as tartrate-resistant acid phosphatase (Hayman et al., 1996) and cathepsin K (Gowen et al., 1999) also produced osteopetrosis. This complements earlier discussed spontaneous osteopetrotic phenotypes produced by interception of pathways generating either protons or chloride necessary for mineral dissolution. 

Hayman, A.R., and Cox, T.M. (2003) Tartrate Resistant Acid Phosphatase Knockout Mice. Journal of Bone and Mineral Research 18,1905-1907. 

Halleen, J.M., Raisanen, S., Salo, J.J., Reddy, S.V., Roodman, G.D., Hentunen, T.A., Lehenkari, P.P., Kaija, H., Vihko, P., and Vaananen, H.K. 1999. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase. J. Biol. Chem. 274, 22907-22910. 

Tartrate-Resistant Acid Phosphatase, Marker of Bone Resorption (TRACP, EC.3.1.3.2 5-TRACP)... 

HI. Halleen, J. M., Karp, M., Viloma, S., Laaksonen, P., Heilman, J., et al., Two-site immunoassays for osteoclastic tartrate-resistant acid phosphatase based on characterization of six monoclonal antibodies. J. Bone Miner. Res. 14,464-469 (1999). 

Bone enzymes are direct products of active osteoblasts (bone ALP) and osteoclasts (tartrate-resistant acid phosphatase). 

Methods for the Determination of Tartrate-Resistant Acid Phosphatase... 

Panteghini M, Pagani F. Reference intervals for two bone-derived enzyme activities in serum bone isoenzyme of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TR-ACP). Clin Chem 1989 35 181-1. 

Bone resorption markers are Listed in Box 49-5. N- and C-telopeptides of type I collagen (NTx and CTx) and deoxypyridinoline are most frequently measured. Other markers include serum tartrate-resistant acid phosphatase (TRAP) and hydroxyproline. Bone resorption markers, apart from TRAP, were initially measured in urine. More recently, methods using serum have been developed for a number of these analytes including N- and C-telopeptides. 

Cheung CK, Panesar NS, Haines C, Masarei J, Swaminathan R. Immunoassay of tartrate-resistant acid phosphatase in serum. Clin Chem 1995 41 679-86. 

Halleen JM, Alatalo SL, Janckila AJ> Woitge HW, Seibel MJ, Vaananen HK. Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption. Clin Chem 2001 47 597-600. 

Kraenzlin ME, Lau KHW, Liang L, Freeman TK, Singer FR, Stepan J, et al. Development of an immunoassay for serum osteoclastic tartrate resistant acid phosphatase. J Clin Endocrinol Metab 1990 71 442-51. 

Nakanishi M, Yoh K, Miura T, Ohasi T, Rai SK, Uchida K. Development of a kinetic assay for band 5b tartrate-resistant acid phosphatase activity in serum. Clin Chem 2000 46 469-73. 

Price CP, Kirwan A, Vader C. Tartrate-resistant acid phosphatase as a marker of bone resorption. Clin Chem 1995 41 641-3. 

Acid phosphatases are enzymes that have been studied extensively due to the fact that their dysregulation is associated with pathophysiological conditions. This characteristic has been exploited for the development of diagnostic and therapeutic methods. As an example, prostatic acid phosphatase was the first marker for metastatic prostate cancer diagnosis and the dysregulation of tartrate resistant acid phosphatase is associated with abnormal bone resorption linked to osteoporosis. 

The pioneering crystallization smdies on prostatic acid phosphatase and mammalian tartrate-resistant acid phosphatase conformed significant milestones towards the elucidation of the mechanisms followed by these enzymes (Schneider et al., EMBO J 12 2609-2615, 1993). Acid phosphatases are also found in nonmammalian species such as bacteria, fungi, parasites, and plants, and most of them share structural similarities with mammalian acid phosphatase enzymes. 

Still there is no official nomenclature for this class of enzymes but there is a consensus in the literature by which the term purple acid phosphatase refers to those metallo-dependent acid phosphatases found in nonmammalian species while the term tartrate-resistant acid phosphatase is kept for those enzymes found in mammals. 

The nature of the metal-ions in the active site also varies between species. Whereas the purple acid phosphatase isolated from red kidney beans (rkbPAP) contains Fe and Zn", the tartrate-resistant acid phosphatase isolated from rat osteoclasts (TRAcP) contains two iron atoms in different oxidation states, an stabilized Fe ion and a redox-active Fe ion. In this way, the ability of the ferrous ion to act as an electron donor confers to the enzyme an alternative function as generator of reactive oxygen species (ROS) [20, 21]. The enzyme may appear in an inactive purple form when the redox-active iron is oxidized to the ferric state, or it can be in an active pink form where the redox-active iron is reduced to the ferrous state [22]. In particular, the tartrate-resistant acid phosphatase isolated from osteoclasts is synthetized as a precursor which is activated by cysteine proteinases resulting in an active two subunit enzyme [23]. 

In vitro studies have shown that TRAcP 5b isoform remains intracellularly in macrophages and dendritic cells which only secrete the TRAcP 5a isoform [25]. Therefore, for clinical determinations it is assumed that the tartrate-resistant acid phosphatase activity associated with bone resorbing osteoclasts derives only from the TRAcP 5 b isoform. 

The tartrate-resistant acid phosphatases showed preferential activity towards esters of aromatic compounds and less towards phosphoanhydrides such as nucleotide triphosphate and diphosphate and phosphotyrosine but not against phosphoserine, phos-phothreonine [26], or aliphatic alcohols [27]. 

The activity of the tartrate-resistant acid phosphatase enzyme is affected by the strength of reducing agents. Whereas mild-reducing agents, such as ascorbate or p-mercaptoethanol, lead to... 

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