Lipids

Question 1

What are the precursors to cholesterol?

Answer 1

acetyl coA, FA, AA

Question 2

What is the rate limiting step in cholesterol synthesis?

Answer 2

HMG-CoA reductase

which is inhibited by statins

Question 3

How do we synthesize mevalonate?

Answer 3

1. 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

Question 4

What happens when cholesterol synthesis is deficient?

Answer 4

smith-lemli-opita syndrome (SLOS)

or embryonic malformation

Question 5

What are the 2 methods of cholesterol esterification and why do we use them?

Answer 5

1. Acyl CoA: cholesterol acyltransferase (ACAT) used for steroid hormones and storage in cells
2. Lecithin: cholesterol acyltransferase (LCAT) is used for cholesterol esterification in HDL

Question 6

Can cholesterol be used for energy?

Answer 6

No, because it cannot be degraded. This is why it must be excreted in the form of bile in feces.

Question 7

Bile salt synthesis

Answer 7

In liver only: cholic acid using cholesterol 7-alpha-hydroxylase (rate limiting step).

The other bile acid is chenodeoxycholic acid

Question 8

Bile salt synthesis

Answer 8

1. Adding glycine to cholic acid = glycocholic acid

2. adding taurine to chenodeoxycholic acid = taurochenodeoxycholic acid

Question 9

How do hormones affect cholesterol synthesis?

Answer 9

1. Insulin actuvates HMG-CoA reductase by dephosphorylating it
2. Glucagon inhibits HMG-CoA reductase by phosphorylating it

Question 10

Which substances signal to stop cholesterol synthesis?

Answer 10

bile salts

cholesterol

Question 11

An excess of intracellular cholesterol signals …

Answer 11

1. an increase in cholesterol ester production

2. a decrease in LDL receptor-mediated endocytosis

Question 12

How do statins work:

Answer 12

1. HMG-CoA analog

2. HMG-CoA reductase inhibitor

Question 13

Which lipoprotein contains mostly TGs?

Answer 13

chylomicrons

Question 14

Which lipoprotein contains TGs and cholesterol?

Answer 14

VLDL (most TG, least CHO), IDL, LDL (least TG, most CHO)

Question 15

Please describe the path of chylomicrons.

Answer 15

1. Chylomicrons are formed in the intestinal cells from HDL proteins
2. Remnant chylomicrons: TGs in chylomicrons are mostly digested, leaving CHO
3. remnant chylomicrons enter the liver

Question 16

Please describe the path of VLDL

Answer 16

1. The liver synthesizes VLDL
2. VLDL Remnants are IDL: TGs are digested, leaving mostly the hydrophilic portions and CHO
3. IDL may be turned into LDL, or return to the liver immediately.
4. LDL returns to the liver or goes to peripheral tissues.

Question 17

Describe HDL’s path

Answer 17

peripheral tissues release HDL back to the liver

Question 18

LPL and Km

Answer 18

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

Question 19

Which enzyme and which Apo protein is used for chylomicron synthesis?

Answer 19

1. Microsomal triglyceride transfer protein (MTP) in the ER

2. Apo B48, vit E

Question 20

What is abetalipoproteinemia?

Answer 20

hypolipoproteinemia caused by loss of function mutations in MTP enzyme (transfers lipids to chylomicrons and VLDL)

Consequences:

1. Low plasma CHO and TG (no chylomicron, no VLDL)
2. Clinical features: steatorrhea and failure to thrive due to fat malabsorption
3. Malabsorption of fat soluble vitamins

Treatment:
low-fat, high-caloric, vitamin-enriched diet

Question 21

What is abetalipoproteinemia?

Answer 21

hypolipoproteinemia caused by loss of function mutations in MTP enzyme (t lipids to chylomicrons and VLDL)

Question 22

Which apo protein is used to tag VLDL, IDL and LDL?

Answer 22

apo B-100

Question 23

What are apo C-II?

Answer 23

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.

Question 24

What is Apo A-I?

Answer 24

found in chylomicrons (because chylomicrons use HDL proteins) and HDL

activator of LCAT