Final answer:
The intracellular concentration of unesterified cholesterol is reduced mainly by suppressing cholesterol biosynthesis via feedback inhibition of HMG-CoA reductase, dietary changes, increased physical activity, and the use of statins and other drugs. Receptor-mediated endocytosis and the conversion of cholesterol into bile acids also play a role in reducing cholesterol levels.
Step-by-step explanation:
Processes Decreasing Intracellular Concentration of Free Cholesterol
The intracellular concentration of unesterified/free cholesterol can be decreased by several processes, including the regulation of cholesterol biosynthesis, dietary modifications, physical activity, and pharmacological interventions. Cholesterol synthesis is primarily regulated at the enzyme HMG-CoA reductase step, where feedback inhibition occurs if cholesterol or its intermediate mevalonate is in excess. This enzyme's activity is reduced by phosphorylation with hormones like glucagon and epinephrine and increased by dephosphorylation.
Dietary changes can significantly impact cholesterol levels. For instance, reducing saturated and trans fats, and incorporating unsaturated fats can lower serum cholesterol levels. Additionally, when blood cholesterol exceeds 150 mg/100 mL, the liver's cholesterol synthesis rate drops significantly, evidencing an innate feedback mechanism. Physical activity also contributes to lower cholesterol levels and improves the LDL:HDL ratio.
Lastly, cholesterol is also removed from the blood via receptor-mediated endocytosis wherein LDL particles are taken up. The excess cholesterol is then converted by the liver into bile acids for excretion. Thus, reducing the absorption of cholesterol in the gut or enhancing its excretion can substantially lower intracellular and blood cholesterol levels.