Metabolism of Lipids: Lipoproteins Flashcards
HDL accept cholesterol from cells through the action of:
Binding Cassette Transporter A1 (ABCA1)
Ligands for binding to LDL receptor and remanant receptor
Found: Remanant, VLDL, LDL, HDL
Apo E
How is cleared the chylomicron remanant?
Cleared from the circulation by the liver cell (hepatocytes) via the chylomicron remnant receptor on the hepatocytes, binding to the apoE on the remnant particle.
Does micelles can be absorbed?
NO!
Only freely dissolved monoglycerides and fatty acids can be absorbed
After digestion, monoglycerides and fatty acids associate with bile salts and phospholipids to form:
Mixed Micelles
Describe the Step 3 of lipid digestion
Phospholipids from the diet as well as bile, mainly LPA, are acylated by 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT) to form phosphatidic acid (PA), which is also converted into TAG.
Chylomicrons enter the lymphatic circulation and make their way via ___________ to the circulation where the duct empties into the ____________in the neck.
Thoracic Lymph Duct, Subclavian Vein in the Neck
Consist in: a core of TGs, cholesteryl esters (CE), and lipid-soluble vitamins, a monolayer membrane of PLs and small amounts of free cholesterol and apoproteins.
Lipoproteins
Structural protein for HDL and activator of hepatic lipase found on HDL.
Apo A-2
Acquire cholesterol from peripheral cells and either transport it by a direct route to the liver or indirectly transfer it to triglyceride-rich particles, chylomicrons, VLDL, or LDL, where they follow the remnant/LDL route
HDL
In the liver the hepatocytes binds the apoE on chylomicrons via the:
LDL receptor (LDL-R)
Are the transporters of dietary lipids (exogenous) to adipose tissue and the liver
Chylomicrons
Describe the Step 2 of VLDL metabolism
In the capillaries of adipocytes, VLDL binds LPL via the apoC-II with the enzyme cleaving the TGs to glycerol and fatty acids to be used by the adipocyte.
Whats the main role of lipoproteins?
Lipoproteins distribute triacylglycerols and cholesterol between the intestine, liver, and peripheral tissues.
Describe the Step 2 of lipid digestion
They are then re-esterified sequentially inside the endoplasmic reticulum by MAG acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) to form TAG.
___________ are ransporter molecules for TGs, PLs, free and cholesteryl esters, and other lipid- soluble nutrients like vitamins A, K, D and E from the blood to different organs and tissues.
Lipoproteins
Where are packed the chylomicrons?
Enterocyte cell lining the small intestine
Structural protein for chylomicrons
Found: Chylomicrons and remanants
Apo B-48
Serve as structural components of membranes, the major source of energy, and precursors to a variety of specialized regulatory molecules, such as steroid hormones, prostaglandins and leukotriens.
Lipids
Describe the Step 1 of the lipid digestion
FAs and MAG enter the enterocytes by transporters, such as intestinal FA-binding protein (IFABP), CD36 and FA-transport protein-4 (FATP4).
Lipoprotein Lipase (LPL) function?
Cleaves the triglycerides in the chylomicron and the glycerol and free fatty acids enter the adipocyte thus depleting the chylomicron of triglyceride content and filling the fat cell with fatty acids
Describe the Step 5 of lipid digestion
Facilitated by microsomal triglyceride transfer protein (MTP), TAG joins CE and apolipoprotein B (ApoB) to form chylomicrons (CM) that enter circulation through the lymph.
LDL Metabolism
Circulating LDL binds to the LDL receptor (LDLr) found in many tissues. The entire LDL is then degraded, providing the cell with cholesterol.
Liver > VLDL > LDL > Liver
What form mixed micelles?
Monoacylglycerol, diacylglycerol and free fatty acids that are released by lipid hydrolysis + bile salts, cholesterol, lysophosphatidic acid and fat- soluble vitamins
Structural protein for Lp(a), is the inhibitor of plasminogen activation
Found: Lp(a)
Apo (a)
How is transported the triacylglycerol?
Triacylglycerols are transported in plasma within lipoprotein particles
Acquisition of triglycerides enlarges the particle further, it now becomes: _____________
HDL-2
Carries mainly TGs and cholesterol esters
VLDL
Lecithin Cholesterol Acyltransferase (LCAT)
Esterified the free cholesterol acquired by the nascent HDL
What two new peripheral apoproteins acquire the chylomicrons in the blood?
apoCII and apoE
Wich molecule can bind to LDL to form a complex that appear atherogenic?
LDL can complex with apo(a) protein to form Lp(a)
The chylomicron will also bind to adipocytes via the apoCII to:
Lipoprotein lipase (LPL)
Essential cofactor for LPL
Found: Chylomicrons, VLDL
Apo C-ll
Fnal steps of HDL Metabolism
- HDL-3 particles bind to the scavenger receptor BI on the hepatocyte membrane and transfer CEs to the liver.
- When the transfer is completed, the size of the HDL particle decreases again.
Structural proteins for HDL and activator of LCAT found in HDL
Apo A-1
Interacts with chylomicrons and VLDL to catalyze the hydrolysis of the triglycerides to form free fatty acids (FFA)
Lipoprotein Lipase (LPL)
Where is completed the digestive process of lipids?
Intestinal lumen
Aided by the _______, HDL transfers some of its cholesteryl esters to chylomicrons, VLDL, and remnant particles in exchange for triglycerides.
CETP
Describe the Step 1 of VLDL metabolism
VLDLs Passes into the blood stream and acquires two further apoC-II and apoE surface apoproteins from HDL molecules
Is the major cholesterol carrier in human blood.
LDL
What is the most ocmmon mutation for LPL deficiency?
Replace the glycine with acid glutamic acid at position 188 in the enzyme (Gly188Glu or G188E).
On the lipoprotein serves as a cofactor for LPL
Apo C-ll
High TG in their blood can lead to: __________
Acute Pancreatitis
Describe the Step 4 of lipid digestion
Dietary CL is acylated by acyl-CoA:cholesterol acyltransferase (ACAT) to cholesterol esters (CE).
VLDL remnant-LDL cascade
Used by the liver provides some cholesterol
How is transported short and medium chain FA?
Short- and medium-chain fatty acids are transported bound to albumin
Molecules that circulate in the blood, carrying TGs, PLs and cholesterol from the liver to other tissues throughout the body
VLDLs
Transport the poorly soluble monoglycerides and fatty acids to the surface of the enterocyte where they can be absorbed, contain gat soluble vitamines and cholesterol.
Micelles
It is an “integral” apoprotein (transmembrane protein) and is a shortened form of apoB-100, being approximately 48% as long
Apo B-48
Inhibitor proteins binding to receptors
Found: Chylomicrons, VLDL, HDL
Apo C-lll
Is structurally similar to LDLs containing an apoB-100 surface protein with an additional apo(a) moiety, giving it prothrombotic capabilities in addition to potential atherogenicity
Lp (a)
What effect has the mutation on LPL gene?
Mutations in the LPL gene reduce or eliminate the activity of lipoprotein lipase, preventing the removing TGs from chylomicrons.
Wich major protein retain LDL?
Retains a single major protein, apoB100, and is removed from circulation by the apoB/E receptor.
what is formed when large emulsions of fat globules are mixed with bile salts and pancreatic lipid digestive enzymes?
Aqueous suspension of small fatty droplets to maximize exposure to the pancreatic lipases for lipid hydrolysis
Activator of LPL and LCAT found in HDL and chylomicrons
Apo A-IV
Structural protein for VLDL and LDL that is also a ligand for binding LDL receptor
Found in: VLDL,IDL,LDL
Apo B-100
Uses ATP as a source of energy and is rate-limiting for the efflux of free cholesterol to apoAI.
Binding cassette transporter A1 (ABCA1)
Cholesteryl esters move into the interior of the particle, which enlarges and becomes spherical - it is now designated: ________
HDL-3
Inhibit plasminogen activation, potentially leading to a tendency for thrombosis, a process known to play a role in acute cardiac events.
Apo (a) because the similarity on structure to Lp (a)
Provides instructions for making two versions of the apolipoprotein B protein, ashort version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100
APOB gene
Triacylglycerides, Phospholipids, Sphingolipids, Cholesterol, Free and Cholesterol esters, Waxes and lipid-soluble vitamins.
Lipids in Human Diet
Provide a continuous source of digested dietary products for absorption at the brush-border membranes of the enterocytes.
Mixed Miscelles
Their main apolipoproteins are apoAI and apoAII, but they also contain apoC and apoE
HDL
Triglyceride is reduced to 20% in the chylomicron the apoCII dissociates from the chylomicron and this reduced triglyceride lipoprotein with only apoB48 and apoE and is now called:
Chylomicron Remanant
_________________ are particles found in plasma, composed of proteins and various classes of lipids.
Lipoproteins
Whats the action of LPL on VLDL?
To produce intermediate-density lipoproteins (IDL), which can be taken up by B-100, E-receptor, or further lipolyzed, to produce LDL.
