Cryptococcal urease is believed to be important for the degradation of exogenous urea that the yeast encounters both in its natural environment and within the human host. Endogenous urea produced by the yeast's own metabolic reactions, however, may also serve as a substrate for the urease enzyme. Using wild-type, urease-deletion mutant and urease-reconstituted strains of Cryptococcus neoformans H99, we studied reactions located up- and downstream from endogenous urea. We demonstrated that urease is important for cryptococcal growth and that, compared to nutrient-rich conditions at 26°C, urease activity is higher under nutrient-limited conditions at 37°C. Compared to cells with a functional urease enzyme, urease-deficient cells had significantly higher intracellular urea levels and also showed more arginase activity, which may act as a potential source of endogenous urea. Metabolic reactions linked to arginase were also affected, since urease-positive and urease-negative cells differed with respect to agmatinase activity, polyamine synthesis, and intracellular levels of proline and reactive oxygen species. Lastly, urease-deficient cells showed higher melanin levels at 26°C than wild-type cells, while the inverse was observed at 37°C. These results suggest that cryptococcal urease is associated with the functioning of key metabolic pathways within the yeast cell.

中文翻译：

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毒性因子脲酶及其在新隐球菌代谢中的未探索作用。

人们认为，隐球菌脲酶对于酵母在其自然环境和人类宿主内遇到的外源尿素的降解很重要。但是，由酵母自身的代谢反应产生的内源尿素也可以用作尿素酶的底物。使用野生型隐球菌的尿素酶缺失突变体和重组尿素酶的菌株H99，我们研究了内源尿素上游和下游的反应。我们证明了脲酶对于隐球菌的生长很重要，并且与26°C的营养丰富的条件相比，在37°C的有限营养条件下，脲酶的活性更高。与具有功能性尿素酶的细胞相比，缺乏尿素酶的细胞具有明显更高的细胞内尿素水平，并显示出更高的精氨酸酶活性，这可能是潜在的内源性尿素来源。与精氨酸酶有关的代谢反应也受到影响，因为脲酶阳性细胞和脲酶阴性细胞在胍丁胺酶活性，多胺合成以及脯氨酸和活性氧种类的细胞内水平方面有所不同。最后，缺乏脲酶的细胞在26°C时显示出比野生型细胞更高的黑色素水平，而在37°C时则相反。