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structure of cholesterol
27-carbon steroid containing 4 fused rings and an alcohol group on carbon 3
where does cholesterol synthesis occur?
cytosol
-what is stage 1 of Step 1 of cholesterol synthesis?
-what is stage 2 of Step 1 of cholesterol synthesis?
-what is stage 3 of Step 1 of cholesterol synthesis?
-which enzyme(s) is/are involved in this step?
-two acetyl-CoA molecules join to form acetoacetyl-CoA after the release of CoA-SH
-acetoacetyl-CoA is converted to HMG-CoA by converting acetyl-CoA to CoA-SH
-HMG-CoA is converted to mevalonate by releasing CoA-SH and converting 2 molecules of NADPH to NADP⁺ (regulated)
-thiolase; HMG-CoA synthase; HMG-CoA reductase
what is Step 2 of cholesterol synthesis?
the 6-carbon mevalonate is converted to a 5-carbon pyrophosphate-activated isoprene using an energy-expensive process, requiring 3 ATPs
what is Step 3 of cholesterol synthesis?
activated isoprene units join in multiple condensation steps to form a 30-carbon squalene
what is Step 4 of cholesterol synthesis?
squalene is oxidized to form an epoxide through the oxidation of NADPH, eventually leading to cyclization and the formation of cholesterol
HMG-CoA reductase is hormonally upregulated by __________ (insulin/glucagon) and downregulated by __________ (isnulin/glucagon)
insulin; glucagon
AMP kinase (AMPK) is activated when there are __________ (low/high) levels of AMP
high
AMPK __________ (activates/inhibits) HMG-CoA reductase
inhibits
what is the oxidized form of cholesterol?
oxysterol
oxysterol allosterically __________ (inhibits/activates) HMG-reductase
inhibits
acyl CoA cholesterol acyl transferase
converts cholesterol to cholesterol esters under high cholesterol conditions by adding a fatty acid to the alcohol group of carbon 3
which three genes of the ER membrane regulate long-term cholesterol levels?
Insig, SCAP, SREBP
Insig, SCAP, and SREBP are __________ (bound/unbound) at high sterol levels
bound
how do Insig, SCAP, and SREBP regulate cholesterol levels under low sterol conditions?
Insig is separated from SCAP and SREBP, and the proteolysis/cleavage of the regulatory domain of SREBP stimulates the transcription of lipid-synthesizing enzymes after the domain travels inside the nucleus
how is Vitamin D₃ synthesized?
7-dehydrocholestrol is converted to Vitamin D₃ using UV light
what is the lipoprotein associated with low-density lipoprotein (LDL) cholesterol?
ApoB-100
what do cholesterol and triacylglycerols (TAGs) use to be exported from the liver?
very low-density lipoproteins (VLDL)
what does lipoprotein lipase do during VLDL transport of TAGs?
it breaks down TAGs in VLDLs to fatty acids and delivers them to tissues
what happens to VLDLs after TAGs are broken down?
they are converted to intermediate-density lipoproteins (ILD) and eventually to low-density lipoproteins (LDL) that contain cholesterols and cholesterol esters
what delivers cholesterol to glands, muscle, and adipose?
LDL
what is the purpose of high-density lipoprotein (HDL)?
it scavenges to destroy and process all VLDL and LDL that did not deliver its contents
function of ApoB-100
it acts as a recognition system for LDL endocytosis into target tissue
atherosclerosis
a disease caused by the buildup of LDL in artery walls, leading to coronary heart disease
what do macrophages do when there is arterial blockages due to LDL buildup?
they form foam cells to target LDLs in artery walls
what happens when HDLs don't clear foam cells?
foam cells will accumulate and lead to plaque formation, resulting in arterial blockages