#5 NS 160 Regulation of Cholesterol Synthesis

#5 NS 160 Regulation of Cholesterol Synthesis - Regulation...

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Unformatted text preview: Regulation of Cholesterol synthesis Cholesterol- regulated control of SREBPs Sterol- dependent degradation of HMG CoA reductase Cholesterol can be derived from the diet or synthesized de novo (liver and intestine) An adult on a low-cholesterol diet typically synthesizes about 800 mg of cholesterol per day. Rate of cholesterol synthesis is highly responsive to the cellular levels of cholester This feedback regulation is mediated primarily by changes in the amount and activity of 3- hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) and the transcription factor Sterol Regulatory Element Binding Protein (SREBP) Regulation of Cholesterol synthesis Expression of many genes involved in cholesterol and lipid synthesis are regulated by a transcription factor termed Sterol Regulatory Element Binding Protein (SREBP) Protein Sensors for Sterols The SREBP system Expression of many genes involved in cholesterol and lipid synthesis are regulated by a transcription factor termed Sterol Regulatory Element Binding Protein (SREBP) Protein Sensors for Sterols The SREBP system SREBPs are cotranslationally inserted into the ER membrane The C-terminus of SREBP binds to Scap (SREBP-clevage- activating protein), which act as sterol sensors Protein Sensors for Sterols The SREBP system In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) Protein Sensors for Sterols The SREBP system ER-Golgi Transport ER-Golgi Transport In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) In the Golgi SREBP is proteolytically processed by two proteases (S1P and S2P) to generated the nuclear form that activates genes for cholesterol synthesis and uptake Protein Sensors for Sterols The SREBP system In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) In the Golgi SREBP is proteolytically processed by two proteases (S1P and S2P) to generated the nuclear form that activates genes for cholesterol synthesis and uptake Protein Sensors for Sterols The SREBP system In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) In the Golgi SREBP is proteolytically processed by two proteases (S1P and S2P) to generated the nuclear form that activates genes for cholesterol synthesis and uptake Protein Sensors for Sterols The SREBP system In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) In the Golgi SREBP is proteolytically processed by two proteases (S1P and S2P) to generated the nuclear form that activates genes for cholesterol synthesis and uptake Protein Sensors for Sterols The SREBP system In sterol depleted cells Scap escorts SREBP to the Golgi by binding to Sec24 (a component of the CopII protein coat) In the Golgi SREBP is proteolytically processed by two proteases (S1P...
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#5 NS 160 Regulation of Cholesterol Synthesis - Regulation...

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