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Structure of Acid Phosphatases

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Phosphatase Modulators

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1053))

Abstract

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 studies 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.

Acid phosphatase (EC 3.1.3.2) enzymes catalyze the hydrolysis of phosphate monoesters following the general equation (1).

$$ \text{Phosphate}\,\text{monoester}+{\text{H}}_{2}\text{O}\,\iff \text{alcohol}+\text{phosphate}$$
(1)

The general classification “acid phosphatase” relies only on the optimum acidic pH for the enzymatic activity in assay conditions using non-physiological substrates. These enzymes accept a wide range of substrates in vitro, ranging from small organic molecules to phosphoproteins, constituting a heterogeneous group of enzymes from the structural point of view. These structural differences account for the divergence in cofactor dependences and behavior against substrates, inhibitors, and activators. In this group only the tartrate-resistant acid phosphatase is a metallo-enzyme whereas the other members do not require metal-ion binding for their catalytic activity. In addition, tartrate-resistant acid phosphatase and erythrocytic acid phosphatase are not inhibited by l-(+)-tartrate ion while the prostatic acid phosphatase is tartrate-sensitive. This is an important difference that can be exploited in in vitro assays to differentiate between different kinds of phosphatase activity. The search for more sensitive and specific methods of detection in clinical laboratory applications led to the development of radioimmunoassays (RIA) for determination of prostatic acid phosphatase in serum. These methods permit the direct quantification of the enzyme regardless of its activity status. Therefore, an independent structural classification exists that helps to group these enzymes according to their structural features and mechanisms. Based on this we can distinguish the histidine acid phosphatases (Van Etten, Ann N Y Acad Sci 390:27–51, 1982), the low molecular weight protein tyrosine acid phosphatases and the metal-ion dependent phosphatases.

A note of caution is worthwhile mentioning here. The nomenclature of acid phosphatases has not been particularly easy for those new to the subject. Unfortunately, the acronym PAP is very common in the literature about purple acid phosphatases and prostatic acid phosphatase. In addition, LPAP is the acronym chosen to refer to the lysophosphatidic acid phosphatase which is a different enzyme. It is important to bear in mind this distinction while reviewing the literature to avoid confusion.

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Authors and Affiliations

  1. Department of Clinical Chemistry, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland

    César L. Araujo & Pirkko T. Vihko

  2. Helsinki University Hospital Laboratory, Helsinki, Finland

    César L. Araujo & Pirkko T. Vihko

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  1. César L. Araujo
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  2. Pirkko T. Vihko
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Editors and Affiliations

  1. Sanford Children's Health Research Ctr., Sanford-Burnham Medical Research Inst., North Torrey Pines Road 10901, La Jolla, 92037, California, USA

    José Luis Millán

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Araujo, C.L., Vihko, P.T. (2013). Structure of Acid Phosphatases. In: Millán, J. (eds) Phosphatase Modulators. Methods in Molecular Biology, vol 1053. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-562-0_11

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  • DOI: https://doi.org/10.1007/978-1-62703-562-0_11

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  • Publisher Name: Humana Press, Totowa, NJ

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