Low Density Lipoprotiens

Question 0

Hyperlipoprotienemia

Answer 0

Elevated levels of lipoprotein in blood
Elevated cholesterol and triglyceride-> arteriolosclerosis early 
Fredricksons classification 
Type 1-> chylomicrons
Type 2a-> LDL
Type 2b-> LDL and VDL
Type 3-> remnants of VLDL and chylomicrons-> most common 
Type 4-> VLDL
Type 5-> chylomicrons and VLDL

Question 1

Role of apolipoprotiens

Answer 1

Apo protiens are essential for the metabolism of lipoproteins
Allow recognition of LPs by enzymes and receptors
LPs carry insoluble lipids in the blood plasma, mainly TH and CE

Question 2

Exogenous lipid transport

Answer 2

Removal of dietary lipids
Chylomicrons-> triglycerides, phospholipids and cholesterol with B-48(genetically related to live b-100 but 48% of size) -> HDL donates apolipoprotien C II and apo E in the lymph-> mature chylomicrons -> transport dietary lipids from intestines to liver, adipose,cardiac and skeletal muscle, lactating mammary gland
At the body sites->
CII-> activates/cofactor for lipoprotien lipase (LPL) on the capillary endothelium-> hydrolyses TGs from chylomicrons and VLDL -> FFA for absorption in to tissues-> chylomicrons remnant-> gives CII back to HDL
Apo E-> recognised by membrane receptors especially on the liver -> chylomicrons remnant recognised and enter by endocytosis

Question 3

Lipoprotein lipase effectiveness at different sites

Answer 3

Adipose LPL has a high Km so is more effective after a meal when there is more fat
Muscle LPL has a low Km so can obtain TGs for energy even when in low cons

Question 4

Endogenous lipid transport

Answer 4

Transport of lipid synthesised in the liver
VLDL-> TG and cholesterol esters generated in liver (from plasma FFA and chylomicrons remnants) and apo B-100-> transports endogenous lipid to tissues-> acquires CII and E from HDL
Apo CII-> LPL breaks down TGs for absorption
Apo CIII-> inhibits LPL so TG hydrolysis dependent on CII:CIII ratio
IDL-> product of LPL processing of VLDL and chylomicrons-> cholesterol rich VLDL and chylomicrons remnants-> endocytosed in to liver via apo E
Or metabolised by hepatic lipase in to LDL-> most cholesterol rich lipoprotien with no apo E -> 40-60% taken up in to liver via apo b100 and hepatic LDL receptors rest by scavenger receptors (non hepatic LDL receptors) mainly on macrophages -> Atheroma-> take up oxidised LDL and migrate in to epithelium

Question 5

HDL

Answer 5

Initially cholesterol free lipoproteins that are synthesised by enters types and the liver
Obtain cholesterol from peripheral tissues and other lipoproteins and transport it to where it is needed and the liver for clearance

Question 6

Hepatic LDL receptor regulation

Answer 6

Up regulated by decreased dietary fat and cholesterol

Down regulated by increased cholesterol and dietary saturated fat delivery to the liver

Question 7

Apo E

Answer 7

On chylomicrons, remnants, VLDL and HDL
LDL receptor ligand -> required for cellular uptake of lipids
LDL r-> degradation of lipoprotein particles -> binds apo B and apo E
LDL receptor related protein -> receptor for apo E on chylomicrons remnants
During LPL degradation of VLDL-> increased ApoE:ApoC ratio-> eventually left with just apo b
299 AA polypeptide -> domain for LDL binding on N terminal between AA 120-150

Question 8

Apo E2

Answer 8

8% of pop
C C
Binds poorly to cell surface receptors -> can’t form salt bridge in the correct location -> too low down in the ligand binding domain
Clear dietary fat more slowly
Early vascular disease
Associated with type 3 hyperlipoprotienemia

Question 9

E2E2 homozygotes

Answer 9

95% of type 3 hyperlipoprotienemia patients are E2/E2-> but only 1% of E2E2 people develop the disease-> must be polygenic
All have raised chylomicrons remnants
Associated with low LDL cholesterol in those who don’t have type III -> all pathways of VLDL and chylomicrons uptake are dysfunctional-> all becomes LDL-> increased chylomicrons remnants-> increased liver cholesterol-> decreased LDLr expression-> decreased cholesterol in liver-> increased LDL expression-> decreased plasma LDL

Question 10

Apo E3

Answer 10

77% of pop
Normal
A and C

Question 11

Apo E4

Answer 11

15%
A A
Arg 122 orientates the side chain of Arg 61 into the aqueous environment-> can interact with glu-255 between N and C terminals
Associated with Alzheimer’s and atherosclerosis

Question 12

Type III hyperlipoprotienemia

Answer 12

Increased chylomicrons remnants and accumulation of B VLDL
Low binding activity decelerates the catabolic change of chylomicrons, VLDL and remnants
Enhanced hepatic LDLr’s lowers LDL cholesterol and increases LDL cholesterol
Unmasked by conditions which repress LDL expression by increasing cholesterol
-> high fat diet, obesity, low oestrogen, diabetes, hypothyroidism
Or the absence of functional LDL R as well