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LIPOPROTEIN, image lipid_intro-Image005, lipid_intro-Image001 - Coggle…
LIPOPROTEIN
APOLIPOPROTEINS
Apo A-II
Structural protein for HDL
Activates hepatic lipase
Apo A-IV
Regulates food intake
Apo A-V
Promotes LPL mediated TG lipolysis
Apo B-48
Structural protein for chylomicrons
Apo B-100
Structural protein
Ligand for LDL receptor
Apo C-I
Activates LCAT
Apo C-II
Co-factor for LPL
Apo C-III
Inhibits LPL and uptake of lipoproteins
Apo E
Ligand for LDL receptor
Apo (a)
Inhibits plasminogen activation
Apo A-I
Activates LDL
Structural protein for HDL
LIPOPROTEIN RECEPTORS AND LIPID TRANSPORTERS
LDL Receptor
Liver
Recognizes Apo B-100 and Apo-E and mediates the uptake of LDL, chylomicron remnants, and IDL.
LDL Receptor Related Protein(LRP)
Liver
Recognizes Apo E and mediates the uptake of chylomicron remnants and IDL.
Class B Scavenger Receptor B1(SR-B1)
Liver, adrenal glands, ovaries, testes, macrophages, and other cells
Mediates the selective uptake of cholesterol esters in liver and facilitates the efflux of cholesterol from cells to HDL in macropages
ATP-Binding Cassette Transporter A1 (ABCA1)
Hepatocytes, enterocytes, macrophages
Mediates the transport of cholesterol and phospholipids from cells to HDL
ATP-Binding Cassette Transporter G1 (ABCG1)
Many different cell types
Mediates the efflux of cholesterol from the cell to HDL particles
ATP-Binding Cassette Transporter G5 and G8 (ABCG5/ABCG8)
Liver and intestine and form a heterodimer
In the intestine, mediate the movement of plant sterols and cholesterol from inside the enterocyte into the intestinal lumen .
In the liver, play a role in the movement of cholesterol and plant sterols into the bile facilitating the excretion of plant sterols.
Niemann-Pick C1-Like 1(NPC1L1)
Intestine
Mediates the uptake of cholesterol and plant sterols from the intestinal lumen into the enterocyte
Classes
Chylomicrons
Chylomicron Remnants
VLDL
IDL
HDL
LDL
Lp (a)
ENZYMES AND TRANSFER PROTEINS INVOLVED IN LIPID METABOLISM
Lipoprotein Lipase(LPL)
This enzyme hydrolyzes the triglycerides carried in chylomicrons and VLDL to fatty acids, which can be taken up by cells
Hepatic Lipase
It mediates the hydrolysis of triglycerides and phospholipids in IDL and LDL leading to smaller particles
Endothelial Lipase
This lipase plays a major role in hydrolyzing the phospholipids in HD
Lecithin: Cholesterol Acyltransferase(LCAT)
It catalyzes the synthesis of cholesterol esters in HDL by facilitating the transfer of a fatty acid from position 2 of lecithin to cholesterol
Cholesterol Ester Transfer Protein(CETP)
Mediates the transfer of cholesterol esters from HDL to VLDL, chylomicrons, and LDL and the transfer of triglycerides from VLDL and chylomicrons to HDL.
EXOGENOUS LIPOPROTEIN PATHWAY
1. FAT ABSORPTION
2. INTESTINAL CELL AND STEROL METABOLISM
3. FORMATION OF CHYLOMICRONS
4. CHYLOMICRONS METABOLISM
Functions
Transport toxic foreign hydrophobic and amphipathic compounds
Transport of lipids from liver to peripheral tissues
Transport of lipids from peripheral tissues to liver and intestine
Absortion and transport of dietary lipids by the small intestine
ENDOGENOUS LIPOPROPTEIN PATHWAY
Liver
VLDL
Muscle and adipose tissues
Fatty acids and IDL
Formation of VLDL
VLDL Metabolism
particles are transported and are hydrolyzed and fatty acids are released.
The amount of lipid available determines whether Apo B-100 is degraded or secreted
LDL Metabolism
LDL are determined by the rate of LDL production and the rate of LDL clearance, both of which are regulated by the number of LDL receptors
the level of hepatic LDL receptors plays a key role in regulating plasma LDL levels.
The levels of LDL receptors in the liver are mainly regulated by the cholesterol content of the hepatocyte
LDL receptor is targeted for degradation by PCSK9, a secreted protein that binds to the LDL receptor and enhances LDL receptor degradation in the lysosomes.
Structure
Central hydrophobic core
Non polar lipids
Primary cholesterol esters
Triglycerides
Hydrophilic membrane
Phospholipids
Free cholesterol
Apolipoproteins
HDL METABOLISM AND REVERSE CHOLESTEROL TRANSPORT
After Apo A-I is secreted, it acquires cholesterol and phospholipids that are effluxed from hepatocytes and enterocytes
newly formed HDL can also obtain cholesterol and phospholipids from chylomicrons and VLDL during their lipolysis by LPL
HDL Cholesterol Esterification
cholesterol in the core of HDL is esterified
LCAT activity is required for the formation of large HDL particles.
HDL2
SRBI
Synthesis of ApoA-1
Apo A-1
Pre-BHDL
HDL3
LCAT
ABCG1
Macrophages
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ABCG4
LCAT
LDL
CETP
ULDL
