Lipoprotein metabolism is the transport of dietary and endogenously derived lipids across different tissues or organs mainly through circulation. Since lipids like triacylglycerol, cholesterol, fatty acids are not soluble in water, their transportation through blood is very difficult. This problem solved by complexing with proteins called apolipoproteins or apoproteins. Together with apoproteins, these lipids are packaged in the form of lipoproteins namely; chylomicron, very low-density lipoprotein [VLDL], low-density lipoprotein [LDL] and high-density lipoprotein [HDL]. So, there are 2 pathways of lipoprotein metabolism.
- Exogenous pathway of lipid transport or metabolism of chylomicron
- Endogenous pathway of lipid transport: metabolism of VLDL, LDL, and HDL
Exogenous pathway of lipid transport
Metabolism and transport of dietary lipids is called exogenous pathway of lipid transport. Triglycerides, phospholipids, cholesterol esters present in the diet are hydrolyzed by lipolytic enzymes in the intestine and absorbed into intestinal mucosal cells. Inside the intestinal mucosal cells, these lipids are packaged along with an apoprotein which is exclusively synthesized there to form chylomicron. Now, this chylomicron transported to lymphatics then onto the thoracic duct and finally to the systemic circulation. In the walls of capillaries or blood vessels, we have an enzyme called lipoprotein lipase which is activated by apo C-II start hydrolyzing triglycerides present in the chylomicron. So, chylomicron becomes smaller and it is called chylomicron remnant which will be taken by liver through LRP or lipoprotein receptor-related protein. Please watch the below-embedded video to understand more regarding chylomicron metabolism.
Endogenous pathway of lipid transport: VLDL and LDL metabolism
In this pathway, lipids primarily derived from liver along with apoproteins synthesized in the liver are packaged in the form of VLDL and released into the circulation where it will convert to initially IDL and then on to LDL by lipoprotein lipase which is present on the walls of capillaries. 1:30 Various lipid synthesized within the liver or endogenously derived lipids by hepatocytes 4:26 Release of nascent VLDL from liver to the circulation 5:10 Conversion of nascent VLDL to mature VLDL by apo E, apo C and circulating HDL with the help of cholesterol ester transfer protein or CETP 6:16 Activation of lipoprotein lipase by apo C-II and conversion of mature VLDL to IDL 7:50 Conversion of IDL to LDL 9:43 Fate of LDL, LDL taken to extrahepatic tissues and liver through receptor-mediated endocytosis through LDL receptors.
HDL Metabolism: Reverse cholesterol transport
In this video, I have explained HDL synthesis as a nascent HDL and maturation of HDL. HDL helps in reverse cholesterol transport from extrahepatic tissues to the liver. There are two transporters or receptors responsible for reverse cholesterol transport by HDL namely, ATP binding cassette transporter A1 or ABCA1 and scavenger receptor B1. Major apolipoprotein or apoprotein present in HDL is apo-AI which is synthesized by both liver and intestinal mucosal cells. Nascent HDL also acquires apo-C and apo-E from the liver. An important enzyme binds to nascent HDL, which is synthesized by liver is LCAT. 1:20 Nascent HDL, phospholipid, cholesterol 4:05 Lecithin cholesterol acyltransferase or LCAT, cholesterol ester, lysolecithin 6:35 Pathway of HDL metabolism 7:45 ABCA1 or ATP binding cassette transporter A1 and SR-B1 or scavenger receptor B1 11:08 HDL 2, the formation of HDL 2 11:38 Formation of HDL 3 or mature HDL with the help of CETP or cholesterol ester transfer protein 12:47 Uptake of HDL by the liver through SR-B1.