Journal
MOLECULES
Volume 28, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/molecules28186667
Keywords
acetyl-CoA; citrate synthase; growth; isocitrate lyase; 2-methylcitrate synthase; 2-methylisocitrate lyase; propionyl-CoA; virulence
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The methylcitrate cycle and the glyoxylate cycle are important carbon metabolic pathways in fungi, which not only convert toxic intermediates into usable substances, but also play important roles in fungal growth, development, and pathogenic processes.
In fungi, the methylcitrate cycle converts cytotoxic propionyl-coenzyme A (CoA) to pyruvate, which enters gluconeogenesis. The glyoxylate cycle converts acetyl-CoA to succinate, which enters gluconeogenesis. The tricarboxylic acid cycle is a central carbon metabolic pathway that connects the methylcitrate cycle, the glyoxylate cycle, and other metabolisms for lipids, carbohydrates, and amino acids. Fungal citrate synthase and 2-methylcitrate synthase as well as isocitrate lyase and 2-methylisocitrate lyase, each evolved from a common ancestral protein. Impairment of the methylcitrate cycle leads to the accumulation of toxic intermediates such as propionyl-CoA, 2-methylcitrate, and 2-methylisocitrate in fungal cells, which in turn inhibits the activity of many enzymes such as dehydrogenases and remodels cellular carbon metabolic processes. The methylcitrate cycle and the glyoxylate cycle synergistically regulate carbon source utilization as well as fungal growth, development, and pathogenic process in pathogenic fungi.
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