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Biochemistry
Published in Ronald Fayer, Lihua Xiao, Cryptosporidium and Cryptosporidiosis, 2007
Similar to other apicomplexans, Cryptosporidium is unable to synthesize purines de novo. However, its purine scavenge pathway is highly streamlined and appears to solely rely on uptake of adenosine from host through a transporter (Figure 3.1). Adenosine is converted to AMP by an adenosine kinase (AK) (Galazka et al., 2006), which in turn is converted to IMP (by AMP deaminase, [AMPDA]), XMP (by IMP dehydrogenase [IMPDH]), and GMP (by GMP synthase [GMPS]). However, unlike other apicomplexans, Cryptosporidium lacks a gene encoding hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT), indicating that GMP may only be made via a simple AMP-to-GMP pathway (Abrahamsen et al., 2004; Striepen and Kissinger, 2004). More surprisingly, CpIMPDH differs from other apicomplexan IMPDHs and is evolutionarily related to ε-proteobacterial homologues (Striepen et al., 2002; Umejiego et al., 2004). For this reason, CpIMPDH is much less sensitive to mycophenolic acid (MPA) than other eukaryotic homologues, including TgIMPDH. In fact, the CpIMPDH gene was first identified unexpectedly by complementation screening of a C. parvum expression library in a ΔHXGPRT strain of T. gondii (Striepen et al., 2002). The assay was originally designed to hunt for the hypothetical CpHXGPRT gene under the selection by MPA. More recently, this enzyme has been expressed as a recombinant protein, and its enzyme kinetics were characterized in detail (Umejiego et al., 2004). Additionally, CpIMPDH was also able to complement the function in an IMPDH-knockout strain of Escherichia coli, which not only confirms the function of this enzyme, but also makes it possible to perform bacterial growth-based high-throughput screening of anti-CpIMPDH compounds for drug development (Umejiego et al., 2004).
Polycyclic musks in the environment: A review of their concentrations and distribution, ecological effects and behavior, current concerns and future prospects
Published in Critical Reviews in Environmental Science and Technology, 2021
Jianv Liu, Wenying Zhang, Qixing Zhou, Qingqin Zhou, Yu Zhang, Linfang Zhu
At the molecular level (Table 6), investigations into the interactive mechanisms between PCMs and the biomacromolecules of organisms are in progress. To protect against the overaccumulation of reactive oxygen species induced by pollution stress, a series of antioxidant mechanisms control the redox balance of cells and reduce oxidative stress and cell damage during the long-term phylogenetic development of organisms. Antioxidant enzyme systems are often used as indicators to monitor the toxic effects of pollutants on organisms. After subchronic exposure to AHTN, the antioxidant enzyme activities of zebrafish were determined, and the results showed that the synergistic cooperation of various parts of the antioxidant system maintained an equilibrium with respect to the production and removal of ROS in cells; thus, zebrafish could be protected from AHTN toxicity (Blahova et al., 2018). As another kind of functional enzyme of invertebrates, higher organisms and plants, AMP deaminase, which plays a critical role in energy metabolism (AMP-DA, AMP-aminohydrolase, EC3.4.5.6.), was examined (Skladanowski, Stepnowski, Kleszczynski, & Dmochowska, 2005), and the results indicated that AMP deaminase activity was inhibited and changed regularly with changes in the concentrations of HHCB, AHTN, MX and MK. In addition to biological enzyme activity studies, some progress has already been made in understanding gene expression changes in test organisms when exposed to PCMs. As an estrogenic effect indicator, estrogen-responsive genes (ERs) (ERα and β) in medaka livers were analyzed after exposure to 500 µg/LAHTN and/or HHCB (Yamauchi et al., 2008). The results showed that the ERα expression level changed markedly with PCM treatment, whereas the ERβ expression level did not respond to these compounds. Similarly, as a hormonal effect indicator, the human thyroid hormone receptor (hTR) was observed following contamination by the PCMs. Although there was an interaction between hERa, hAR and the tested PCMs, changes in the expression level of hTR beta were not obvious (Mori et al., 2007). The above two cases indicated that the gene expression level may not be easily changed when an individual is exposed to natural PCM contamination. Parolini et al. (2015) also observed this phenomenon because no obvious gene damage was found when Dreissena polymorpha was exposed to HHCB and AHTN. However, in contrast to the gene data in the study, the protein carbonyl content (PCC) levels and DNA strand breaks were significantly increased. The metabolism and mode action of PCMs have also been investigated (Fernandes et al., 2013).