Nozaki Tomoyoshi, Ali Vahab, Tokoro Masaharu
Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Adv Parasitol. 2005;60:1-99. doi: 10.1016/S0065-308X(05)60001-2.
Sulfur-containing amino acids play indispensable roles in a wide variety of biological activities including protein synthesis, methylation, and biosynthesis of polyamines and glutathione. Biosynthesis and catabolism of these amino acids need to be carefully regulated to achieve the requirement of the above-mentioned activities and also to eliminate toxicity attributable to the amino acids. Genome-wide analyses of enzymes involved in the metabolic pathways of sulfur-containing amino acids, including transsulfuration, sulfur assimilatory de novo cysteine biosynthesis, methionine cycle, and degradation, using genome databases available from a variety of parasitic protozoa, reveal remarkable diversity between protozoan parasites and their mammalian hosts. Thus, the sulfur-containing amino acid metabolic pathways are a rational target for the development of novel chemotherapeutic and prophylactic agents against diseases caused by protozoan parasites. These pathways also demonstrate notable heterogeneity among parasites, suggesting that the metabolism of sulfur-containing amino acids reflects the diversity of parasitism among parasite species, and probably influences their biology and pathophysiology such as virulence competence and stress defense.
含硫氨基酸在多种生物活性中发挥着不可或缺的作用，包括蛋白质合成、甲基化以及多胺和谷胱甘肽的生物合成。这些氨基酸的生物合成和分解代谢需要得到精细调控，以满足上述活性的需求，并消除氨基酸所致的毒性。利用多种寄生原生动物的基因组数据库，对参与含硫氨基酸代谢途径（包括转硫作用、硫同化从头合成半胱氨酸、甲硫氨酸循环和降解）的酶进行全基因组分析，结果显示原生动物寄生虫与其哺乳动物宿主之间存在显著差异。因此，含硫氨基酸代谢途径是开发针对原生动物寄生虫所致疾病的新型化疗和预防药物的合理靶点。这些途径在寄生虫之间也表现出显著的异质性，这表明含硫氨基酸的代谢反映了寄生虫物种间寄生现象的多样性，并且可能影响它们的生物学特性和病理生理学，如毒力和应激防御能力。
