Lecture 7

Question 1

Cholesterol modification to form bile acids.

Answer 1

Hydroxylation, side chain cleavage, conjugation to glycine or taurine.

Question 2

What do all steroids have in common?

Answer 2

Cholesterol moiety.

Question 3

Which cell type must diet-derived lipids enter to be synthesized into macromolecular forms?

Answer 3

Enterocytes.

Question 4

Where do chylomicrons originate?

Answer 4

Only from the intestine.

Question 5

Where can excess dietary cholesterol mix in with de novo cholesterol?

Answer 5

In the small intestine.

Question 6

Dyslipidemias.

Answer 6

Abnormal lipid concentration in the blood. Different types: hypertriglyceridemia, hypercholesterolemia. Can be genetic or acquired.

Question 7

Abetalipoproteinia: an example of hypocholesteroemia.

Answer 7

B lipoprotein is missing. Low to undetectable levels of circulating chylomicrons due to malabsorption of fat and fat-soluble vitamins. Solution: limit triglyceride intake to medium chains (not long) and less than 15 g per day. Individuals live, but are very sick.

Question 8

Hypocholesterolemia.

Answer 8

Very low or no chylomicrons, absorption in the intestine is not good, packaging of fats is not good, there can be complete absence of bile acids (though the individual would not survive).

Question 9

Symptoms of abetalipoproteinemia.

Answer 9

Chromic diarrhea (steatorrhea), rhinitis pigmentosa (because the individual cannot absorb fat-soluble vitamin A, ataxia, star-shaped RBCs (Membranes of phosphatidylcholine are not well made).

Question 10

Name a lipid metabolizing enzyme.

Answer 10

ACAT.

Question 11

Lipid carrier proteins.

Answer 11

MTP, Apo 48.

Question 12

Name a fatty acid transporter.

Answer 12

CD36.

Question 13

In the absence of ACAT…

Answer 13

You cannot convert cholesterol into cholesteryl esters.

Question 14

MTP is required for…

Answer 14

Transport of triglycerides and cholesteryl esters between intracellular membranes (it is a carrier protein). It is essential for chylomicron assembly.

Question 15

Membrane-bound receptors on the surface of enterocytes.

Answer 15

NPC1L1 (cholesterol receptor), FATP4 and CD36 (fatty acid receptors), and MFSD2A (phospholipid receptor).

Question 16

Ezetimibe.

Answer 16

It can block cholesterol absorption without affecting the absorption of other lipids. Ezetimibe is a competitive inhibitor with cholesterol for the NPC1L1 binding site.

Question 17

Familial hypercholesterolemia (FH).

Answer 17

Studied using fibroblasts (skin cells); found the molecular mechanism related to cholesterol transport, biosynthesis, etc.

Question 18

Genetic metabolic disorders.

Answer 18

1 gene can code for many enzymes. Can be inherited: defects in specific genes are passed on to the next generation.

Question 19

Encode project.

Answer 19

Most of the genome is composed of regulatory elements. The DNA double helix can be packaged into chromatin to shut down transcription; methylation can also affect transcription and translation.

Question 20

Name on shut-down technique of DNA.

Answer 20

Methylation.

Question 21

Long-range regulatory elements.

Answer 21

They make instructions to make proteins.

Question 22

Epigenetic modification.

Answer 22

The entire genetic information is in on chromosome. Access to the information can be hindered by methylation or acetylation of the histones so the DNA cannot sit properly.

Question 23

Purpose of epigenetic modification.

Answer 23

A mechanism for controlling the use of genetic information during the lifetime of the organism, as well as the next generation. Certain regulatory regions in the parents are marked by the system to be passed on to the next generation; nutrition is a strong regulator of marking the genome. These markings are not permanent.

Question 24

What influences the marking of the genome in epigenetic modification?

Answer 24

Nutritional status.

Question 25

Familial Hypercholesterolemia (FH).

Answer 25

Lipoproteins are isolated from the fibroblasts of patients and are purified. The metabolism of cholesterol can be observed: through the use of isotopes.

Question 26

Clinical features of FH.

Answer 26

High concentration of cholesterol in the blood, fasting plasma is milky due to high lipid content; a normal individual would have yellow fasting plasma. Cholesterol deposits in the skin: xanthelasmas or xanthomas.

Question 27

What is the usefulness of growing fibroblasts from an FH individual in the lab?

Answer 27

You can subject the cells to different conditions and study their responses.

Question 28

What can be found in lipoproteins?

Answer 28

Triacylglycerols, apolipoproteins, cholesteryl esters, phospholipids, etc.

Question 29

Radioactive tracers added to lipoproteins.

Answer 29

H3 or I125 can be added on fatty acyl chains or cholesterol moiety. You can follow the pathway of a specific type of lipoprotein.

Question 30

Use of radioactive tracers: effect of LDL on metabolism of cholesterol.

Answer 30

We can see how a normal cell binds LDL, whereas an FH cell does not. We can see the FH cells do not have a lot of LDL inside. FH cells do not have much hydrolysis.

Question 31

Hydrolysis of Apo B results in…

Answer 31

Amino acids.

Question 32

Hydrolysis of cholesteryl esters results in…

Answer 32

Cholesterol.

Question 33

Conclusions of FH cells regarding LDL.

Answer 33

FH cells are unable to bind, internalize, or metabolize LDL.