Question

The liver takes up cholesterol for excretion and metabolism from three
different lipoprotein particles (LDL, chylomicron remnants and HDL).
Describe the discovery, structure and functional characteristics of the
three receptors involved. Where appropriate, include examples of
genetic mutations that helped identify functional domains within each
receptor, and hence provided insight into uptake mechanisms.

Answer 1

ANS

Liver uses cholesterol for the excretion and metabolism from mainly three lipoprotein particles which are LDL, chylomicron remnants and HDL. Lipoproteins are also called as apolipoproteins and can be differentiated by their density, and degree of lipids are affected by the lipoprotein density. LDL (low density lipoprotein) which is used to process the cholesterol in the cell, when triacylglycerol is removed from VLDL these particles are remodeled and changes into LDL in liver. LDL is used to deliver the cholesterol to cells, for synthesis of steroid hormones which is used by endocytosis and then the LDL binds with specific LDL receptor gets into the endocytic vesicle. By the hydrolysis process of endolysosome, and LDL receptor releases cholesterol in the cell. Chylomicrons are synthesized by lipid enterocytes and gets absorbed in small intenstine. Chylomicrons delivers the energy rich triacylglycerol to the cells with the action of lipoprotein lipase enzyme and this enzyme digests the triacylglycerol to the fatty acids and monoglycerides which are oxidized in the adipose. HDL (High density lipoprotein) removes excess cholesterol from body through liver and converts bile into bile. HDL works on the reverse cholesterol transport pathway process where HDL synthesized by the liver and small intestine collects in the cholesterol and turns into mature HDL.

Receptors (LDL, Chylomicrons and HDL) receptors are involved in the genetic mutations and identify functional domains such as – SARA2 gene form the mutations in the chylomicrons and involved in the transportation of chylomicron by enterocyte secretory pathway. R-BI receptor binds with the ligands and plays role in binding with the high affinity with the HDL lipoprotein. By this cholesteryl esters are delivered to the liver for formation of bile acid.