Intro.
HDLs are formed in the blood by addition of lipid to Apo-AI (woah new apolipoprotein). HDLs transfer cholesterol from peripheral tissue to the liver.
HDLs.
HDLs serve many important functions such as:
Reservoir for apolipoproteins.
As mentioned previously, HDL provides Chylomicrons and VLDLs with Apo-CII and Apo-E. (Apo-CII for LPL activation and Apo-E for receptor-mediated endocytosis of Chylomicron and VLDL remnants.)
Uptake of cholesterol.
Origin and function.
Nascent HDLs are disc-shaped and formed mainly of Apo-A1. Nascent HDL roams the blood and picks up cholesterol along the way through ABCA-1 on peripheral cells. It also picks up cholesterol from foam cells (macrophages) protecting the body from atherosclerosis.
Esterification.
The cholesterol the HDLs uptake is immediately esterified by LCAT which is activated by Apo-A1. As cholesterol esters accumulate it goes form nascent HDL -⇒ -⇒ . The latter of which transfers it to the liver through SRB-1 (which binds HDL) on liver cells. Or through VLDL particles through CETP enzyme. Since VLDLs are catabolized by the liver, the cholesterol esters are ultimately taken up by the liver.
Dyslipidemia.
Hypolipoproteinemia.
- Defect in loading of Apo-B. (deficiency in Chylomicrons, VLDLs, LDLs)
- Low blood TAGs. Liver and Intestinal accumulation of TAGs.
Familial Alpha-lipoprotein deficiency.
- Defect in loading of Apo-A1. (deficiency in HDL)
- High blood TAGs (absent Apo-CII, inactive LPL) and low LDL levels.
Familia lipoprotein lipase deficiency. (Type I)
- Defect in LPL or deficiency in Apo-CII causing inactive LPL.
- Slow clearance of chylomicrons and VLDL, Low LDL and HDL. (no risk of hypercholesterolemia)
Familial hypercholesteremia. (Type II)
- Defect in LDL receptors or mutation in Apo-B100. (Bad VLDLs)
- High LDL levels and hypercholesterolemia.
Familial hyperlipoproteinemia. (Type III)
- Defect in Apo-E. (low clearance of remanent)
- Hypercholesterolemia, increased chylomicron and VLDL remnants.
Familia hypertriacylglycerolemia. (Type IV)
- Increased VLDL.
- Increased cholesterol.