Metabolism of CHolesterol, Plasma Lipoproteins and Steroids

4 fused rings, a hydrocarbon tail, OH groups on C-3 and a double bond at C-5 to C-6--------reactive sites.

all c-atoms of cholesterol come from acetate and reducing equivalents from NADPH
-------driven by ATP hydrolysis and AcCoA

cytoplasm and er of cells

form HMG-CoA from acetyl CoA via HMG-CoA synthase

FORMING MEVALONATE from HMG CoA and 2 NADPH.

subsequent steps use ATP and decarboxylation to form isopentylpyrphosphate. (5 carbon unit) ISOPRENE UNIT

in the synthesis of ubiquinone, dolichol, carotene, and isoprenoids

form 10c and 15 c compunds, and finally two farnysyl 15cs form squalene 30c linear compound,

uses NADPH and O2 to form cyclized LANOSTEROL from the squalene. Finally, a series of reactions trim the the 30c to 27c and modify the structure to form cholesterol.

is regulated by: SREBP on gene transcription. Rate of translation, rate of degradation of the enzyme.
Glucagon---phosphorylates and inactivates
INSULIN---dephosphorylates and activates.
STATINS---reversible inhibitors of HMG CoA reductase.

controls 30 genes (srebp) dedicated to the synthesis and uptake of cholesterol, fatty acids, TAGS, and PHOSPHOLIPIDS as well as the production of NADPH.

is enhanced by srebp1 binding to sterol regulatory elements SREs upstrme of the reductase genes.

ER where it is bound to SCAP by its regulatory domain called REG. When cholesterol levels fall, the complex moves to the GOLGI where Srebp undergoes two proteolytic cleavages. THIS FRESS THE DNA BINDING DOMAIN to go to the nucleus and bind to the SRE.

1a-low level but activates cholesterol and fatty acid synthesis. lc and 2 are the predominat forms.

fatty acid biosynthesis

cholesterol metabolism . ALSO important for the expression of the LDL receptor and the scavenger receptor B1.

activates for both cholesterol and fatty acid metabolism......

based on changes in cholesterol levels in the cell via binding to FXR (all) and LXR (liver)

mimics HMG but is not and results in enzyme HMG reductase inhibtion. This FORCES CELLS IN PERIPHERAL TISSUE TO TAKE UP CIRCULATING LDL TO GET CHOLESTEROL. LOWERS LDL LEVELS DRAMATICALLY, and VLDL AND IDL MODESTYL, WHILE STIMULATING HDL. MAY BE ANTI INFLAMMATORY. MAY CAUSE RHABDOMYOLOSIS AN MYOSITIS.