Biochem - Metabolism (Cholesterol synthesis, Lipid transport, & Familial dyslipidemias)

Question 1

What is the rate-limiting step of cholesterol synthesis, and what enzyme catalyzes it? What substance induces the activity of this enzyme?

Answer 1

Rate-limiting step is catalyzed by HMG-CoA reductase (induced by insulin), which converts HMG-CoA to mevaolonate

Question 2

What is LCAT, and what role does it play in cholesterol synthesis? What portion of cholesterol participates in its role?

Answer 2

2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)

Question 3

What is the mechanism of Statins? Give an example of a Statin.

Answer 3

Statins (e.g., lovastatin) competitively and reversibly inhibit HMG-CoA reductase.

Question 4

What role does pancreatic lipase play in lipid transport?

Answer 4

Degradation of dietary triglycerides (TG) in small intestine

Question 5

What role does lipoprotein lipase (LPL) play in lipid transport? Where are they found?

Answer 5

Degradation of TC circulating in chylomicrons and VLDLs. Found on vascular endothelial surface.

Question 6

What role does Hepatic TG lipase (HL) play in lipid transport?

Answer 6

Degradation of TG remaining in IDL

Question 7

What role does hormone-sensitive lipase play in lipid transport?

Answer 7

Degradation of TG stored in adipocytes

Question 8

What role does LCAT play in lipid transport?

Answer 8

Catalyzes esterification of cholesterol

Question 9

What role does cholesterol ester transfer protein (CETP) play in lipid transport?

Answer 9

Mediates transfer of cholesterol esters to other lipoprotein particles

Question 10

Draw a diagram demonstrating the interconnections of lipid transport, including and labeling the following involved body parts: (1) Intestine (2) Liver (3) Adipose tissue (4) Capillary (5) Peripheral tissues (with LDL receptors). Also include the lipid transport steps that flow between them.

Answer 10

See p. 117 in First Aid 2014 for visual near top/middle of page

Question 11

What are 2 major kinds of receptors on the liver involved in lipid transport?

Answer 11

(1) LDL receptors (2) Remnant (chylomicron remnants) receptors

Question 12

Draw a diagram depicting the general actions of LCAT & CETP plus the organs involved.

Answer 12

See p. 117 in First Aid 2014 for visual near bottom/middle of page

Question 13

Name 5 major apolipoproteins?

Answer 13

(1) E (2) A-1 (3) C-II (4) B-48 (5) B-100

Question 14

What is the function of apolipoprotein E?

Answer 14

Mediates remnant uptake

Question 15

Which of the following describes apolipoprotein E: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?

Answer 15

(1) Yes (2) Yes (3) Yes (4) Yes (5) No (6) Yes

Question 16

What is the function of apolipoprotein A-I?

Answer 16

Activates LCAT

Question 17

Which of the following describes apolipoprotein A-I: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?

Answer 17

(1) Yes (2) No (3) No (4) No (5) No (6) Yes

Question 18

What is the function of apolipoprotein C-II?

Answer 18

Lipoprotein lipase cofactor

Question 19

Which of the following describes apolipoprotein C-II: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?

Answer 19

(1) Yes (2) No (3) Yes (4) No (5) No (6) Yes

Question 20

What is the function of apolipoprotein B-48?

Answer 20

Mediates chylomicron secretion

Question 21

Which of the following describes apolipoprotein B-48: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?

Answer 21

(1) Yes (2) Yes (3) No (4) No (5) No (6) No

Question 22

What is the function of apolipoprotein B-100?

Answer 22

Binds LDL receptor

Question 23

Which of the following describes apolipoprotein B-100: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?

Answer 23

(1) No (2) No (3) Yes (4) Yes (5) Yes (6) No

Question 24

What are the components of lipoproteins?

Answer 24

Lipoproteins are composed of varying proportions of cholesterol, TGs, and phospholipids

Question 25

Which 2 kinds of lipoproteins carry the most cholesterol?

Answer 25

LDL and HDL carry most cholesterol

Question 26

Where does LDL versus HDL transport cholesterol?

Answer 26

LDL transports cholesterol from liver to tissues; HDL transports cholesterol from periphery to liver; Think: "LDL is Lousy, HDL is Healthy"

Question 27

What are 2 functions of chylomicrons?

Answer 27

Delivers dietary TGs to peripheral tissue. Divers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triaglycerols.

Question 28

What secretes chylomicrons?

Answer 28

Secreted by intestinal epithelial cells

Question 29

What is the function of VLDL?

Answer 29

Delivers hepatic TGs to peripheral tissue

Question 30

What secretes VLDL?

Answer 30

Secreted by liver

Question 31

How is IDL formed?

Answer 31

Formed in the degradation of VLDL

Question 32

What is the function of IDL?

Answer 32

Delivers TGs and cholesterol to liver

Question 33

What is the function of LDL?

Answer 33

Delivers hepatic cholesterol to peripheral tissues

Question 34

What forms LDL? How is LDL taken up by target cells?

Answer 34

Formed by hepatic lipase modification of IDL in the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.

Question 35

What are 2 major functions of HDL?

Answer 35

(1) Mediates reverse cholesterol transport from periphery to liver. (2) Acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism).

Question 36

What secretes HDL? What effect does alcohol have on HDL synthesis?

Answer 36

Secreted from both liver and intestine. Alcohol increases synthesis.

Question 37

What is the name of type I familial dyslipidemia? What substances have an increased blood level?

Answer 37

I - Hyperchylomicronemia; Chylomicrons, TG, cholesterol

Question 38

What is the name of type IIa familial dyslipidemia? What substances have an increased blood level?

Answer 38

IIa - Familial Hypercholesterolemia; LDL, cholesterol

Question 39

What is the name of type IV familial dyslipidemia? What substances have an increased blood level?

Answer 39

IV - Hypertriglyceridemia; VLDL, TG

Question 40

What is the mode of inheritance for the following familial dyslipidemias: (1) Type I - Hyperchylomicronemia (2) Type IIa - Familial Hypercholesterolemia (3) Type IV - Hypertriglyceridemia.

Answer 40

(1) Autosomal recessive (2) Autosomal dominant (3) Autosomal dominant

Question 41

What defects may cause Type I familial dyslipidemia (Hyperchylomicronemia)?

Answer 41

Lipoprotein lipase deficiency or altered apolipoprotein C-II

Question 42

What are 3 clinical findings associated with Type I familial dyslipidemia (Hyperchylomicronemia)? How does this disorder affect the risk for atherosclersois?

Answer 42

Causes (1) pancreatitis, (2) hepatosplenomegaly, and (3) eruptive/pruritic xanthomas (no increased risk for atherosclerosis)

Question 43

What is the defect that causes Type IIa familial dyslipidemia - Familial Hypercholesterolemia?

Answer 43

Absent or defective LDL receptors

Question 44

For Familial Hypercholesterolemia, what is the cholesterol level for heterozygotes versus homozygotes? Also estimate the incidence of heterozygote versus homozygote.

Answer 44

Heterozygotes (1:500) have cholesterol ~ 300 mg/dL; Homozygotes (very rare) have cholesterol ~ 700+ mg/dL.

Question 45

What are 3 clinical findings associated with Type IIa familial dyslipidemia - Familial Hypercholesterolemia?

Answer 45

Causes accelerated atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus

Question 46

What is the defect in Type IV familial dyslipidemia - Hypertriglyceridemia?

Answer 46

Hepatic overproduction of VLDL

Question 47

What clinical condition can Type IV familial dyslipidemia - Hypertriglyceridemia cause?

Answer 47

Causes pancreatitis