Lipoproteins

Question 1

4 types of lipoproteins

Answer 1

• chylomicrons
• VLDL
• HDL
• LDL

Question 2

Which lipoproteins predominantly transfer cholesterol

Answer 2

• HDL

- LDL

Question 3

Which lipoproteins predominantly transfer triacylglycerol

Answer 3

• Chylomicrons

- VLDL

Question 4

During low energy circumstances TG is mobilized from adipose tissue as fatty acids and transported on

Answer 4

• Albumin

Question 5

Do medium and short chain fatty acids need to be carried on lipoproteins?

Answer 5

• No

Question 6

Chylomicrons

Answer 6

• largest and the most bouyant of the lipoproteins, due to the large amount of triacylglycerol present in the non-polar core of the lipoprotein
• come from dietary sources
• contain ApoB48 apoproteins, which are synthesized and packaged with nascent chylomicrons in the intestinal epithelial cells
• acquire apoproteins ApoCII and ApoE from HDL

Question 7

VLDL

Answer 7

• 2nd largest lipoprotein
• contains a large amount of TG, but not as much TG as Chylomicrons
• contain ApoB100 apoproteins, which are synthesized and packaged with nascent VLDL in liver cells
• acquire ApoCII and ApoE from HDL
• liver synthesizes fatty acids from glucose and packages them as triglycerides in VLDL

Question 8

LDL

Answer 8

• smaller and less dense, having the least amount of TG and the largest amount of cholesterol esters
• derived from VLDL
  
  • after VLDL releases the majority of their TG, they become Intermediate density lipoproteins (IDL), and with further loss of TG, the IDL become LDL
• contains ApoB100, but they transfer back ApoCII and ApoE to the HDL lipoproteins
• deliver cholesterol to tissues
• LDL that is delivered to tissues does not pose a threat of atherosclerosis, but increased LDL remaining in the bloodstream is the basis of coronary artery disease
• All cells in the body can take up LDL through specialized LDL receptors
  
  • recognize ApoB-100 and uptake by receptor-mediated endocytosis

Question 9

HDL

Answer 9

• very small, highly dense lipoproteins, having few TG and large amounts of cholesterol esters and protein, depending on their life cycle
• contain ApoA apoproteins as well as other apoproteins, such as ApoCII and ApoE
• two major functions:
  
  • carry cholesterol away from the tissues to the liver
  • carry and distribute apoproteins to other lipoproteins for their function
• newly secreted HDL particles acquire additional cholesterol and phospholipids via ABCA-1 on peripheral tissue
• also carries:
  
  • Phosphatidyl choline:Cholesterol Acyl-Transferase (PCAT)
  • Cholesterol Ester Transfer Protein (CETP)
  • Phospholipid Transfer Protein (PLTP)

Question 10

Apolipoproteins

Answer 10

• proteins that combine with lipoproteins either during packaging or are acquired later
• Apoproteins destined to be packaged with lipoproteins are synthesized on the rough ER and are packaged with lipids,
  cholesterol, and fat-soluble vitamins in the Golgi apparatus
• some apoproteins function as cofactors for enzymatic activity or are themselves enzymes, others assist in transferring lipids among various lipoproteins, and still others are
  recognized by cellular receptors to allow the lipoprotein to dock and be taken up by the cell

Question 11

ApoA-1

Answer 11

Lipoprotein expressed on:
- HDL
- chylomicrons 
Function 
- activates LCAT; ligand for HDL receptor

Question 12

ApoB-100

Answer 12

Lipoprotein expressed on: 
- LDL
- VLDL
- IDL 
Function: 
- LDL receptor ligand

Question 13

ApoB-48

Answer 13

Lipoprotein expressed on:
- chylomicrons
- chylo remnants 
Function: 
- Chylo assembly and secretion; dietary lipids

Question 14

ApoC-II

Answer 14

Lipoprotein expressed on:

• VLDL
• HDL
• Chylomicrons

Function:
- activates LPL, transfers b/w HDL and VLDL/chylomicrons

Question 15

ApoE

Answer 15

Lipoprotein expressed on:

• VLDL
• HDL
• Chylomicrons
• chylo remnants
• LDL

Function:
- Hepatic receptor ligand for chylomicron, LDL; is recycled b/w HDL and VLDL/chylomicrons

Question 16

Lipoprotein Lipase (LPL)

Answer 16

• an enzyme located on the
  inner leaflet of the endothelial cells lining the bloodstream
• breaks down the TG into three fatty acids plus glycerol
• LPL isozymes are regulated differently depending on the tissue
  
  • insulin activates LPL in adipocytes and in the capillary endothelium
  • By contrast, insulin has been shown to decrease expression of muscle LPL
  • Muscle and myocardial LPL is instead activated by glucagon and adrenaline

Question 17

chylomicron remnants

Answer 17

• chylomicrons that have lost most of their triglycerides

Question 18

Acyl CoA:Cholesterol Acyltransferase (ACAT)

Answer 18

• converts excess cellular cholesterol to cholesterol esters for storage
• attaches a fatty acid from fatty acyl-CoA to the free hydroxyl of cholesterol to form cholesterol ester, the non-polar storage form

Question 19

Regulatory functions of cholesterol:

Answer 19

• ↑ cholesterol inhibits HMG CoA Reductase enzyme
• ↑ cholesterol inhibits LDL receptor biosynthesis
• ↑ cholesterol activates ACAT (acyl CoA cholesterol acyltransferase)

Question 20

ATP-binding cassette-A-1 (ABCA-1)

Answer 20

• one of a large family of transfer proteins that use energy in the form of ATP in the transfer of bile, cholesterol, ions, and many drugs across membranes
• ABCA-1 was the first discovered member of this family, and its function is to provide cholesterol to HDL

Question 21

Phosphatidyl choline:Cholesterol Acyl-Transferase (PCAT)

Answer 21

• carried by HDL
• converts cholesterol to cholesterol ester by transferring a fatty acyl group from the phospholipid phosphatidyl choline to cholesterol to form cholesterol ester

Question 22

Cholesterol Ester Transfer Protein (CETP)

Answer 22

• carried on HDL
• synthesized by many tissues,
  including liver and adipose
• exchanges cholesterol ester on HDL for triglyceride on VLDL
• pro- and anti-atherogenic functions
• Deficiency in CETP is associated with increased HDL levels

Question 23

Phospholipid Transfer Protein (PLTP)

Answer 23

• exchanges triglyceride on HDL for phospholipids on VLDL
• ApoE may be essential for stabilizing
• involved in HDL and VLDL remodeling, including conversion of HDL to large HDL2 and small lipid-poor HDL particles
• pro- and anti-atherogenic functions
• Deficiency is associated with decreased HDL and ApoA-1 levels.

Question 24

Cholesterol

Answer 24

• LDL delivers its cholesterol to the peripheral tissues, including a major user, the adrenal gland
  
  • converted to various cholesterol-derived hormones

Synthesized from acetyl CoA:

• first reaction forms hydroxyl-methyl-glutaryl-CoA (HMG-CoA)
• next step—converting HMG-CoA to mevalonic acid—is catalyzed by the enzyme HMG-CoA reductase
  
  • This is the committed step toward cholesterol synthesis and the regulated, rate-limiting step
• HMG-CoA reductase is inhibited by its ultimate product, cholesterol
  
  • This enzyme is the target of the statin drugs
• A series of cycling reactions results in Lanosterol, and finally Cholesterol

Question 25

Atherosclerosis

Answer 25

- Atherosclerosis, coronary heart disease (CHD), and coronary artery disease (CAD) - hallmark of CHD is the presence of excess LDL in circulation

Question 26

Familial Hypercholesterolemia

Answer 26

- genetic abnormality will result in increased circulating LDL - affects the synthesis and/or expression of LDL receptors on cell surfaces * Without these receptors, LDL levels and therefore cholesterol levels rise in the bloodstream

Question 27

Plasma LDL profile is characterization

Answer 27

characterized on the basis of size and density into two patterns: - large, buoyant LDL (pattern A) - small, dense LDL (pattern B) * Small, dense LDL (sd-LDL) penetrates more readily into the subintimal spaces, binds more tightly to proteoglycans in the ECM, therefore remaining longer in the ECM, and these types LDL are oxidized more rapidly than the larger LDL particles

Question 28

Genetic causes of hyperlipidemia

Answer 28

- Familial LPL deficiency (A type I hyperlipidemia) - PCAT deficiency (“Fish Eye Dz”) (A type II hyperlipidemia) HDL) - Familial ApoCII Deficiency (A type V hyperlipidemia) - Familial Defective ApoB100 (A type IIa hyperlipidemia) - Familial Hypercholesterolemia (A type IIa hyperlipidemia) - Polygenic Hypercholesterolemia

Question 29

Familial LPL deficiency

Answer 29

- defect in lipoprotein lipase * results in hypertriglyceridemia * Yields elevated chylomicrons * Autosomal recessive * Causes infantile pancreatitis, eruptive xanthomas, hepatomegaly, lipemia retinalis

Question 30

PCAT deficiency (“Fish Eye Dz”)

Answer 30

defect in PCAT - PCAT converts amphipathic cholesterol to non-polar cholesterol esters, thereby changing the shape of nascent HDL from pancake to spherical - Results in hypercholesterolemia (w/ unrecyclable HDL) - Yields elevated VLDL and total cholesterol - Causes corneal opacities, renal failure, vascular disease

Question 31

Familial ApoCII Deficiency

Answer 31

Deficient ApoCII - Autosomal recessive (RARE) - Yields severe hypertriglyceridemia, w/ ⇧ VLDL, chylo - Causes pancreatitis

Question 32

Familial Defective ApoB100

Answer 32

deficiency of ApoB100 - Autosomal Dominant - Results in hypercholesterolemia - Yields elevated plasma LDL - Causes vascular disease (atherosclerosis)

Question 33

Familial Hypercholesterolemia

Answer 33

deficiency of LDL receptors - Autosomal Dominant - Results in hypercholesterolemia - Yields elevated plasma LDL - Causes early SEVERE vascular disease - xanthomas

Question 34

Polygenic Hypercholesterolemia

Answer 34

The number one cause for hypercholesterolemia multiple genetic influences in combination environmental and other causes from underlying disorders - Yields elevated LDL +/- other anomalies - Causes vascular disease

Question 35

Cholesterol Screening

Answer 35

- cholesterol is ≥ 200 mg/dL, then HDL and TG should be checked - LDL is calculated from these values using the following formula: * Total cholesterol = LDL + TG/5 + HDL

Question 36

CHD Risk factors

Answer 36

- age * Male- 45yr. * Female- 55yr., premature menopause - family history of premature CHD - smoking - hypertension - HDL-cholesterol <35mg/dL - diabetes - obesity