Which of the following best explains the mechanism by which insulin action can result in increased hepatic cholesterol biosynthesis?
A) insulin action results in phosphorylation of SCAP leading to increased release of SREBP-1c
B) insulin action results in reduced levels of cAMP with consequent reduction in active PKA-mediated phosphorylation of SCAP
C) insulin action results in reduced levels of cAMP with consequent reduction in active PKA-mediated phosphorylation of HMG-CoA reductase
D) insulin action causes reduced levels of cAMP, which lead to reduced PKA-mediated phosphorylation of protein phosphatase inhibitor 1 (PPI-1)
E) insulin action leads to tyrosine phosphorylation of AMPK, causing loss of the AMPK-mediated inhibition of HMG-CoA reductase

Question

Quizplus · Accepted Answer

One of the effects, within cells such as hepatocytes, of insulin activation of its receptor is activation of phosphodiesterase. Phosphodiesterase catalyzes the hydrolysis of cAMP to AMP. Reduced levels of cAMP lead to decreased activation of PKA. With respect to cholesterol biosynthesis, PKA normally phosphorylates PPI-1, which when phosphorylated prevents phosphate removal from HMG-CoA reductase (HMGR) by HMGR phosphatase. The reduction in the activity of PPI-1 results in increased HMGR phosphatase activity. Removal of phosphates from HMGR returns it to its more active state. Thus, the net effect of insulin is an increase in the synthesis of cholesterol via its effects on HMGR activity.

Which of the Following Best Explains the Mechanism by Which