Sterol biosynthesis in yeast. 3-Hydorxy-3-methylglutaryl-Coenzyme A reductase as a regulatory enzyme

Anaerobically and aerobically grown yeast contains 3-hydroxy-3-methylglutaryl-CoA reductase, which is located in the mitochondrial fraction of the cell. Anaerobically grown yeast has a low specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase and a low sterol content. Aeration of this yeast in buffer, without growth, results in an increase in the specific activity of the enzyme, which is paralleled by an increase in the sterol content. This induction has an oscillatory profile with yeast grown anaerobically for 24 h and a linear pattern with cells grown anaerobically for 72 h. With the latter type of yeast, glucose is necessary for an induction, whereas with the other yeast an induction occurs with and without glucose. By an anaerobic incubation in buffer of the yeast grown anaerobically for 24 h, the oscillatory profile can be transformed into a linear one. The extent of induction of the reductase is strictly dependent on the concentration of glucose present. Sterols increase in whole cells, but they do not increase in the mitochondrial fraction. The induction of 3-hydroxy-3-methylglutaryl-CoA reductase is strongly inhibited by cycloheximide, but is not affected by chloramphenicol. The induction of the enzyme is closely connected with the glucose metabolism of the cell; fructose, mannose, and ethanol can also induce the reductase.