**Metabolic Adaptation of Isocitrate Lyase in the Yeast Pathogen** *Candida albicans*

Doblin Sandai

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http://dx.doi.org/10.5772/62406

#### **Abstract**

The *ICL1* gene, which encodes the glyoxylate cycle enzyme isocitrate lyase (Icl1), is re‐ quired for the growth of *Candida albicans* on non-fermentable carbon sources and for this yeast to be virulent. The aim of this study is to test the stability of the Icl1 enzyme in re‐ sponse to glucose. Glucose was found to trigger the degradation of the *ICL1* but the CaIcl1 was not destabilized by glucose. When CaIcl1 was expressed in *Saccharomycess cer‐ evisiae*, it was not degraded in response to glucose, suggesting that CaIcl1 has lost the mo‐ lecular signal that triggers destabilization in response to glucose. However, when ScIcl1 was expressed in *C. albicans* it was rapidly degraded in response to glucose indicating that *C. albicans* has retained the molecular apparatus for glucose-accelerated degradation of target proteins. ScIcl1 degradation was slowed in Ca*ubi4/ubi4* in which ubiquitin-medi‐ ated protein turnover is reduced. Furthermore, the addition of putative ubiquitination site to the carboxyl-terminus of CaIcl1 led to the glucose-accelerated degradation of this protein. *C. albicans* has retained the apparatus for ubiquitin-mediated degradation of tar‐ get protein in response to glucose. However, CaIcl1 has lost the Ubi-site that mediate glu‐ cose accelerated protein degradation, thereby allowing *C. albicans* to simultaneously assimilate alternative carbon sources and glucose.

**Keywords:** Glyoxylate cycle, isocitrate lyase (Icl1), metabolic adaptation, virulence, path‐ ogenicity
