Lipids Flashcards
What are the precursors to cholesterol?
acetyl coA, FA, AA
What is the rate limiting step in cholesterol synthesis?
HMG-CoA reductase
which is inhibited by statins
How do we synthesize mevalonate?
- 2 acetyl coA acetoacetyl-coA -HMG-CoA synthase-> HMG-CoA -HMG-CoA reductase-> mevalonate
the last step uses 2 NADPH in order to remove the CoA-SH and reduce HMG-CoA
What happens when cholesterol synthesis is deficient?
smith-lemli-opita syndrome (SLOS)
or embryonic malformation
What are the 2 methods of cholesterol esterification and why do we use them?
- Acyl CoA: cholesterol acyltransferase (ACAT) used for steroid hormones and storage in cells
- Lecithin: cholesterol acyltransferase (LCAT) is used for cholesterol esterification in HDL
Can cholesterol be used for energy?
No, because it cannot be degraded. This is why it must be excreted in the form of bile in feces.
Bile salt synthesis
In liver only: cholic acid using cholesterol 7-alpha-hydroxylase (rate limiting step).
The other bile acid is chenodeoxycholic acid
Bile salt synthesis
- Adding glycine to cholic acid = glycocholic acid
2. adding taurine to chenodeoxycholic acid = taurochenodeoxycholic acid
How do hormones affect cholesterol synthesis?
- Insulin actuvates HMG-CoA reductase by dephosphorylating it
- Glucagon inhibits HMG-CoA reductase by phosphorylating it
Which substances signal to stop cholesterol synthesis?
bile salts
cholesterol
An excess of intracellular cholesterol signals …
- an increase in cholesterol ester production
2. a decrease in LDL receptor-mediated endocytosis
How do statins work:
- HMG-CoA analog
2. HMG-CoA reductase inhibitor
Which lipoprotein contains mostly TGs?
chylomicrons
Which lipoprotein contains TGs and cholesterol?
VLDL (most TG, least CHO), IDL, LDL (least TG, most CHO)
Please describe the path of chylomicrons.
- Chylomicrons are formed in the intestinal cells from HDL proteins
- Remnant chylomicrons: TGs in chylomicrons are mostly digested, leaving CHO
- remnant chylomicrons enter the liver
Please describe the path of VLDL
- The liver synthesizes VLDL
- VLDL Remnants are IDL: TGs are digested, leaving mostly the hydrophilic portions and CHO
- IDL may be turned into LDL, or return to the liver immediately.
- LDL returns to the liver or goes to peripheral tissues.
Describe HDL’s path
peripheral tissues release HDL back to the liver
LPL and Km
LPL of heart and muscle has low Km, meaning that they metabolize TG at a low level
LPL of adipocytes has a high Km, meaning that they metabolize TG at a high level
Which enzyme and which Apo protein is used for chylomicron synthesis?
- Microsomal triglyceride transfer protein (MTP) in the ER
2. Apo B48, vit E
What is abetalipoproteinemia?
hypolipoproteinemia caused by loss of function mutations in MTP enzyme (transfers lipids to chylomicrons and VLDL)
Consequences:
- Low plasma CHO and TG (no chylomicron, no VLDL)
- Clinical features: steatorrhea and failure to thrive due to fat malabsorption
- Malabsorption of fat soluble vitamins
Treatment:
low-fat, high-caloric, vitamin-enriched diet
What is abetalipoproteinemia?
hypolipoproteinemia caused by loss of function mutations in MTP enzyme (t lipids to chylomicrons and VLDL)
Which apo protein is used to tag VLDL, IDL and LDL?
apo B-100
What are apo C-II?
Apolipoprotein C-II or apolipoprotein C2 is a protein that is a component of very low density lipoproteins and chylomicrons.
This protein activates the enzyme lipoprotein lipase in capillaries.
Mutations in this gene cause hyperlipoproteinemia type IB, characterized by xanthomas, pancreatitis, and hepatosplenomegaly, but no increased risk for atherosclerosis. Lab tests will show elevated blood levels of triglycerides, cholesterol, and chylomicrons.
What is Apo A-I?
found in chylomicrons (because chylomicrons use HDL proteins) and HDL
activator of LCAT
