LDL and Tangier Disease

Question 1

What is the origin, role and metabolic fate of HDL?

Answer 1

HDL is formed by the liver and the intestines and it produces ApoA1. ApoA1 will combine cholesterol with phospholipids at the plasma membrane to produce discoidal nascent HDL

Question 2

What is LCAT?

Answer 2

LCAT converts discoidal HDL to HDL3. HDL3 contains more cholesteryl esters.

LCAT also catalyzes below reaction:
Lecithin + Cholesterol –> Lysolecithin + Cholesterol Esters

Question 3

What is reverse cholesterol transport?

Answer 3

Reverse cholesterol transport is a metabolic pathway where excess cholesterol in peripheral tissues is transported to the liver for elimination from the body.

Question 4

How does HDL mediate reverse cholesterol transport?

Answer 4

1. HDL3 and HDL2 transfer their cholesteryl esters to VLDL or LDL or IDL, in exchange for TG or PL. VLDL or LDL or IDL is then recognized by the LDLR in the liver. The transfer reaction is then catalyzed by CHOLESTEROL ESTER TRANSFER PROTEIN

Question 5

What is HDL receptor and what tissues express the HDL receptor?

Answer 5

HDL Receptor is SR-BI. It is in the plasma membranes of liver cells and adrenal cortex cells for catabolism and reutilization of CE.

Question 6

Describe the involvement of CETP in reverse cholesterol transport

Answer 6

CETP is a drug target for raising cholesterol ester rich HDL

Question 7

What is Tangier disease?

Answer 7

Individuals with Tangier disease have large tonsils, hypocholesterolemia.

Question 8

What is familial HDL deficiency?

Answer 8

Homozygotes of Tangier Disease have absence of plasma HDL and ApoAI, low plasma LDL levels and hypertriglyceridemia. Have an accumulation of cholesterol esters in the macrophages of tissues.
Defects in ABCA1 cause this

Question 9

What does the ABCA1 gene product do?

Answer 9

ABCA1 transports both PL (directly) and cholesterol (indirectly) to Apo1. Failure to lipidate apolipoproteins by the APCA1 pathway leads to rapid catabolism of apo1 and accumulation of sterol esters in tissues

Question 10

What are ABC transporters?

Answer 10

ABC Transporters are a superfamily of proteins that use ATP as a source of energy to transport substrates between different cellular compartments and from the cell.