Freitas-Mesquita Anita Leocadio, Meyer-Fernandes José Roberto
Medical Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Subcell Biochem. 2014;74:217-52. doi: 10.1007/978-94-007-7305-9_10.
Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.
外切酶可定义为膜结合蛋白,其活性位点面向细胞外环境。在锥虫中,这些酶的生理作用仍有待完全阐明;然而,许多重要事件已经与它们相关,例如寄生虫在其复杂生命周期中的存活以及宿主感染的成功建立。本章重点介绍两类显著的外切酶:外切核苷酸酶和外切磷酸酶,总结它们在利什曼原虫属和锥虫属中的存在情况及其可能的生理作用。外切核苷酸酶的特征在于其水解细胞外核苷酸的能力,在嘌呤能信号传导中起重要作用。通过这些外切酶的作用,寄生虫能够调节宿主免疫系统,从而导致寄生虫感染成功。此外,外切核苷酸酶还参与嘌呤补救途径,作用于生成能够通过特殊转运体穿过质膜的核苷。在大量致病生物中存在的另一种重要外切酶是外切磷酸酶。这些酶能够水解细胞外磷酸化底物,释放可被细胞内化的游离无机磷酸,通过磷酸转运体穿过质膜。外切磷酸酶也参与寄生虫在宿主细胞中的入侵和存活。对于这些酶在寄生虫中的作用,还提出了几种其他功能,例如参与它们的增殖、分化、营养和保护。在此背景下,本章概述了与利什曼原虫和锥虫寄生虫中外切核苷酸酶和外切磷酸酶活性的发生相关的最新发现。