Metabolism: Cholesterol Flashcards
What are some end products of cholesterol?
- steroid hormones
- bile acids
- cholesterol esters
Which cholesterol derivative is a reversible reaction?
only cholesterol esters
How is cholesterol obtained?
- dietary cholesterol => chylomicrons
2. TAG breakdown
How does cholesterol travel in the blood?
in VLDL, which turn into LDL
What is mevalonate?
- intermediate of cholesterol synthesis
- produced by HMG-CoA Reductase
What is the rate-limiting step in cholesterol synthesis?
HMG-CoA Reductase in synthesizing mevalonate
Describe the mechanism/reaction of cholesterol synthesis.
- 3 acetyl-CoA => 1 HMG-CoA
- HMG-CoA Reductase => mevalonate
- => squalene
- cyclization => lanosterol
- decarboxylation => cholesterol
Describe activation of HMG-CoA Reductase.
- insulin activates the enzyme because you want to use the excess glucose to generate cholesterol
Describe inhibition of HMG-CoA Reductase.
- mevalonic acid negative inhibition of enzyme
- cholesterol negative inhibition
- cholesterol decreases transcription/translation, increases degradation
- allosteric inhibition via cAMP and glucagon
Describe HMG-CoA Reductase regulation on the transcriptional, translational, enzyme stability, and phosphorylation level.
- transcription is decreased by cholesterol
- translation is decreased by mevalonate derivatives
- degradation is increased by cholesterol and mevalonate
- phosphorylation = inactivation (cAMP, glucagon)
How is cholesterol used to synthesize bile acids?
via 7-alpha-hydroxylase
occurs in liver
Describe the function of ACAT.
ACAT = acyl-CoA Cholesterol Acyl Transferase
makes cholesterol esters for storage
How do statins work?
- statins inhibit HMG-CoA Reductase
- causes decreased production of cholesterol
- lower cholesterol levels leads to upregulation of LDL receptors
- increases LDL uptake in cells, effectively reducing circulating LDL levels
What is one situation where statins cannot work?
if patient has defect or deficiency in LDL receptors, statins will not work because even though you have less cholesterol, you will not impact the amount of LDL in the blood
- also take diet into consideration
In general, excess cholesterol intake leads to…
- inhibits cholesterol synthesis
- promotes cholesterol utilization in the liver
