Rate limiting step in cholesterol synthesis

Regulation of Cholesterol SynthesisThe regulatory enzyme is HMG CoA reductase. Long-term regulation involves regulation of transcription of the gene for HMG CoA reductase. When sufficient cholesterol is present in the cell, transcription of the gene for HMG CoA reductase is suppressed, and cellular synthesis of cholesterol is decreased. When cholesterol in diet is low, synthesis is increased Cholesterol regulates the expression of HMG CoA reductase gene and LDLR (LDL receptor) gene. A specific recognition sequence known as the sterol regulatory element (SRE) is present in DNA. SRE binding by sterol regulatory element binding protein (SREBP) is essential for the transcription of these genes. When cholesterol levels are sufficiently high, the SREBP remains as an inactive precursor. The SREBP cleavage activator protein (SCAP), is an intracellular cholesterol sensor. When cholesterol is less, SCAP escos SREBP to Golgi bodies. Two Golgi proteases (S1P and S2P) sequentially cleave the SREBP to a protein which binds to SRE and activates transcription of HMG CoA reductase geneFor the transcription of these genes. When cholesterol levels are sufficiently high, the SREBP remains as an inactive precursor. The SREBP cleavage activator protein (SCAP), is an intracellular cholesterol sensor. When cholesterol is less, SCAP escos SREBP to Golgi bodies. Two Golgi proteases (S1P and S2P) sequentially cleave the SREBP to a protein which binds to SRE and activates transcription of HMG CoA reductase gene Insulin and thyroxine increase the activity of HMG CoA reductase Coisol and glucagon decrease its activityRef: D.M Vasudevan, 6th edition, page no: 149