Flashcards in Biochem - Metabolism (Cholesterol synthesis, Lipid transport, & Familial dyslipidemias) Deck (47):
What is the rate-limiting step of cholesterol synthesis, and what enzyme catalyzes it? What substance induces the activity of this enzyme?
Rate-limiting step is catalyzed by HMG-CoA reductase (induced by insulin), which converts HMG-CoA to mevaolonate
What is LCAT, and what role does it play in cholesterol synthesis? What portion of cholesterol participates in its role?
2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)
What is the mechanism of Statins? Give an example of a Statin.
Statins (e.g., lovastatin) competitively and reversibly inhibit HMG-CoA reductase.
What role does pancreatic lipase play in lipid transport?
Degradation of dietary triglycerides (TG) in small intestine
What role does lipoprotein lipase (LPL) play in lipid transport? Where are they found?
Degradation of TC circulating in chylomicrons and VLDLs. Found on vascular endothelial surface.
What role does Hepatic TG lipase (HL) play in lipid transport?
Degradation of TG remaining in IDL
What role does hormone-sensitive lipase play in lipid transport?
Degradation of TG stored in adipocytes
What role does LCAT play in lipid transport?
Catalyzes esterification of cholesterol
What role does cholesterol ester transfer protein (CETP) play in lipid transport?
Mediates transfer of cholesterol esters to other lipoprotein particles
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.
See p. 117 in First Aid 2014 for visual near top/middle of page
What are 2 major kinds of receptors on the liver involved in lipid transport?
(1) LDL receptors (2) Remnant (chylomicron remnants) receptors
Draw a diagram depicting the general actions of LCAT & CETP plus the organs involved.
See p. 117 in First Aid 2014 for visual near bottom/middle of page
Name 5 major apolipoproteins?
(1) E (2) A-1 (3) C-II (4) B-48 (5) B-100
What is the function of apolipoprotein E?
Mediates remnant uptake
Which of the following describes apolipoprotein E: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?
(1) Yes (2) Yes (3) Yes (4) Yes (5) No (6) Yes
What is the function of apolipoprotein A-I?
Which of the following describes apolipoprotein A-I: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?
(1) Yes (2) No (3) No (4) No (5) No (6) Yes
What is the function of apolipoprotein C-II?
Lipoprotein lipase cofactor
Which of the following describes apolipoprotein C-II: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?
(1) Yes (2) No (3) Yes (4) No (5) No (6) Yes
What is the function of apolipoprotein B-48?
Mediates chylomicron secretion
Which of the following describes apolipoprotein B-48: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?
(1) Yes (2) Yes (3) No (4) No (5) No (6) No
What is the function of apolipoprotein B-100?
Binds LDL receptor
Which of the following describes apolipoprotein B-100: (1) Chylomicron (2) Chylomicron remnant (3) VLDL (4) IDL (5) LDL (6) HDL?
(1) No (2) No (3) Yes (4) Yes (5) Yes (6) No
What are the components of lipoproteins?
Lipoproteins are composed of varying proportions of cholesterol, TGs, and phospholipids
Which 2 kinds of lipoproteins carry the most cholesterol?
LDL and HDL carry most cholesterol
Where does LDL versus HDL transport cholesterol?
LDL transports cholesterol from liver to tissues; HDL transports cholesterol from periphery to liver; Think: "LDL is Lousy, HDL is Healthy"
What are 2 functions of chylomicrons?
Delivers dietary TGs to peripheral tissue. Divers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triaglycerols.
What secretes chylomicrons?
Secreted by intestinal epithelial cells
What is the function of VLDL?
Delivers hepatic TGs to peripheral tissue
What secretes VLDL?
Secreted by liver
How is IDL formed?
Formed in the degradation of VLDL
What is the function of IDL?
Delivers TGs and cholesterol to liver
What is the function of LDL?
Delivers hepatic cholesterol to peripheral tissues
What forms LDL? How is LDL taken up by target cells?
Formed by hepatic lipase modification of IDL in the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.
What are 2 major functions of HDL?
(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).
What secretes HDL? What effect does alcohol have on HDL synthesis?
Secreted from both liver and intestine. Alcohol increases synthesis.
What is the name of type I familial dyslipidemia? What substances have an increased blood level?
I - Hyperchylomicronemia; Chylomicrons, TG, cholesterol
What is the name of type IIa familial dyslipidemia? What substances have an increased blood level?
IIa - Familial Hypercholesterolemia; LDL, cholesterol
What is the name of type IV familial dyslipidemia? What substances have an increased blood level?
IV - Hypertriglyceridemia; VLDL, TG
What is the mode of inheritance for the following familial dyslipidemias: (1) Type I - Hyperchylomicronemia (2) Type IIa - Familial Hypercholesterolemia (3) Type IV - Hypertriglyceridemia.
(1) Autosomal recessive (2) Autosomal dominant (3) Autosomal dominant
What defects may cause Type I familial dyslipidemia (Hyperchylomicronemia)?
Lipoprotein lipase deficiency or altered apolipoprotein C-II
What are 3 clinical findings associated with Type I familial dyslipidemia (Hyperchylomicronemia)? How does this disorder affect the risk for atherosclersois?
Causes (1) pancreatitis, (2) hepatosplenomegaly, and (3) eruptive/pruritic xanthomas (no increased risk for atherosclerosis)
What is the defect that causes Type IIa familial dyslipidemia - Familial Hypercholesterolemia?
Absent or defective LDL receptors
For Familial Hypercholesterolemia, what is the cholesterol level for heterozygotes versus homozygotes? Also estimate the incidence of heterozygote versus homozygote.
Heterozygotes (1:500) have cholesterol ~ 300 mg/dL; Homozygotes (very rare) have cholesterol ~ 700+ mg/dL.
What are 3 clinical findings associated with Type IIa familial dyslipidemia - Familial Hypercholesterolemia?
Causes accelerated atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus
What is the defect in Type IV familial dyslipidemia - Hypertriglyceridemia?
Hepatic overproduction of VLDL