Describe how the high level of cholesterol metabolism can be regulated: a. At the transcriptional level (Sterol dependent regulation)b. At the hormonal level
a. In mammals, intracellular levels of cholesterol and fatty acids are controlled through a feedback regulatory system mediated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs). SREBPs are synthesized as inactive precursors bound to membranes of the endoplasmic reticulum. When cells are deprived of cholesterol and fatty acids, NH2-terminal fragments of SREBPs become proteolytically released from membranes and migrate to the nucleus to activate transcription of genes required for lipid synthesis and uptake. Conversely, lipid repletion inhibits proteolytic processing of SREBPs and thereby suppresses lipid accumulation.
b. Cholesterol homeostasis is tightly regulated by a group of endocrine hormones under physiological conditions. Circulating hormones regulate cholesterol metabolism by altering levels of relative genes either through their interactions with nuclear receptors or by interfering with bile acid signaling pathways. Cortisol, glucocorticoids, and insulin counterregulatory hormone, glucagon have an inhibitory effect.