HDL and Tangier Disease

Question 1

describe reverse cholesterol transport

Answer 1

pathway where excess lipids are cleared from the periphery and brought back to the liver for elimination

liver and intestines create apoA1 proteins. this combines w/ phospholipids and cholesterol in the periphery to from discoidal nascent HDL.

the enzyme LCAT converts discoidal nascent HDL into HDL3, which contains more cholesterol esters and is spherical

LCAT then converts HDL3 to HDL2 by adding more cholestersol esters, which is then delivered to the liver

Question 2

describe the 2 methods of deliver for HDL cholesterol

Answer 2

1. HDL3 and 2 are recognized by the HDL receptor (SR-B1) in the liver and adrenal cortex and are metabolized for the reutilization of cholesterol esters
2. cholesterol ester transfer protein transfers cholesterol esters to VLDL, LDL, or IDL in exchange to triglycerides or phospholipids, and they are received by LDL receptors

Question 3

describe Tangier disease

Answer 3

rare genetic disease where the ABCA transporter does not transfer cholesterol to ApoA1, causing low levels of HDL and cellular accumulation of cholesterol

signs include enlarged spleen, liver, ocular abnormalities, orange tonsils etc.

Question 4

describe the structure of ABCA

Answer 4

ATP dependent protein comprised of a single strand. can be organized into 2 6-membrane spanning helicies, each with an ATP binding site, and a hydrophobic regulator site in between

ABCA draws from pools of excess cholesterol intracellularly, but it inclear how this is monitored

Question 5

describe genetic regulation of ABCA

Answer 5

the ABCA gene has a direct repeat response element called DR-4 in the promotor, which can bind LXR or RXR or both. both upregulate expression of ABCA and are synergistic.

LXR responds to oxysterols
RXR response to 9-cis-retinoic acid