Lipid Transport And Storage I

Front 1

Types of lipoproteins and their main functions, what they carry
-origins
-cycles of where it comes from and where it goes or is recycled to

Back 1

1. Chylomicrons: transport exogenous (from intestine) TAG to muscles for energy or adipose for storage; highest TAG, lowest cholesterol; chylomicron remnants go to liver

2. LDL: delivers cholesterol (and cholesteryl esters) from liver to peripheral tissues; low TAG, highest cholesterol

3. HDL: delvers cholesterol from peripheral tissues to liver for elimination; more protein than LDL; high choesterol, lowest TAG; **reverse cholesterol transport

4. VLDL: transports endogenous TAG (from liver) to muscles for energy and adipose for storage (lower density b/c less protein); high TAG, low cholesterol; VLDL remnants (IDL) can be converted to LDL which goes to tissues or liver, or IDL goes straight to liver

Origins:
Liver= VLDL, LDL derived from VLDL, HDL
Intestine= Chylomicrons, HDL, small amount of VLDL

Front 2

Structure of lipoproteins
-what the structures are made of
-defining characteristics of lipoproteins

Back 2

CORE= hydrophobic layer; TAG and cholesterol ester

SHELL= hydrophilic layer; amphipathic apolipoproteins, phospholipids, and cholesterol; polar portions exposed on surface to allow it to be soluble in aqueous solution

Defining characteristics:
-apolipoproteins are different/characteristic of the type of lipoprotein

-electrophoretic mobility:
-HDL migrates furthest toward + electrode (anode) (b/c most phospholipids)
-followed by VDL and LDL
-Chylomicrion remains at - electrode (cathode)

Front 3

Apolipoproteins (apoproteins)
-where are they made
-roles

Back 3

-made in liver and small intestine
-Roles: assembly, secretion, peripheral metabolism, and clearance of lipoproteins
-cofactors for enzymes
-- C-II for lipoprotein lipase
-- A-1 for lecithin: cholesterol acyltransferase (functions in HDL to esterfiy free cholesterol)
-inhibitors for enzymes:
-- Apo A-II and Apo C-III for lipoprotein lipase
--Apo C-I for cholesteryl estertransferase
-are ligands for interaction with lipoprotein receptors:
-- Apo B-100
-- Apo E for LDL
-- Apo A-I for HDL receptor

Front 4

Types of Apoproteins
-where are they made
-in which lipoproteins are types A and B found?
-major function of each type

Back 4

Lipoprotein A found in: HDL
Lipoprotein B (B-100) found in: LDL, VLDL,
-chylomicrons have truncated form of Apo B (B-48)


Type A (I and II)
-made in liver and small intestine
-major apoprotein of HDL (HDL= "alpha-lipoprotein")
-also part of cylomicrons
-major function: activates cholesterol-lecithin transferase (LCAT), which esterifies free cholesterol in HDL (A II is a LCAT coactivator)
-also acts as a ligand to interact with HDL receptors on target cells

Type B (B-100 and B-48)
-Apo B-100 made in liver
-VLDL (IDL) packing and secretion, cholesterol clearance contains LDL receptor binding domain (LDL= "beta-lipoprotein")

-Apo B-48 made in intestine (mRNA editing from same mRNA as B-100)
-chylomicron packing and secretion, cholesterol clearance lacks LDL receptor binding (LRP= LDL receptor RELATED protein)
-**chylomicrons and VLDL contain Apo B-48 (b/c both can be derived from small intestine)

Type C
-major function: enzyme activator/inhibitor, freely transfer b/t lipoproteins
-found in VLDL, HDL, and cylomicrons
-Apo C I= activates LCAT (esterfies free cholesterol)
-Apo CII= activates lipoprotein lipase (LPL; hydrolyzes triglyceride (TG) in VLDL and chylomicrons to glycerol and FA; *glycerol goes to liver to make TG and FA goes to muscle and adipose)
-Apo C III= inhibits LPL, hepatic uptake of triglyceride-rich lipoproteins for metabolism

Type E
-found in VLDL (IDL), chylomirons+remnants, and HDL
-activates LPL
-controls receptor binding of remnant particles
-ligand for LDL and hepatic chylomicron remnant receptors, cholesterol clearance

Front 5

Metabolism of Chylomicrons
-where are they made
-what do they carry to tissues
-what is their fate?

Back 5

-assembled in intesine mucosal cells
-carries dietary TG, C, and CE to peripheral tissues
-CMs degraded by LPL to from CM remnants
CM remnants removed from blood= Apo E binds to receptor on liver and endocytosed in
-Vesicles fuse with lysosome= Apoproteins, CE, and lipids are degraded to release AA, C, and FA

Contains:
-Apo A and B-48= packing and secretion from intestine
-Apo C and E= acquired from HDL
-Apo CII and E= activate LPL, CM remnants formed
-Apo CI= activates LCAT to esterfy free cholesterol
-Apo E of CM remnants binds to LRP on liver and gets degraded

Front 6

Metabolism of VLDL and Production of LDL

Back 6

VLDL: made in liver, carries TG and cholesterol from liver to muscle and fat
-LDL: (beta-lipoproteins) final stage in catabolism of VLDL, delivers cholesterol to tissues

VLDL:
-contains Apo B-100= packing and secretion from liver, LDL receptor binding domain
-Apo C and E= acquired from HDL, activates LPL
-LPL hyrolyzes VLDL to make FA for tissues, glycerol for liver, and IDL
-IDL= remnant that makes LDL for goes to liver to be degraded to release FA and cholesterol
-LDL= contains Apo B-100 and E as a receptor binding domain so it can bind to tissues or liver to deliver cholesterol

**VLDL and LDL bind to membrane with ApoB/E receptor (chylomicron just has a Apo E receptor on liver)

Front 7

Metabolism of HDL in reverse cholesterol transport
-steps in cholesterol transport to liver
-roles of SR-B1

Back 7

-moves cholesterol from tissues to liver for elimination as bile or bile acids

Steps in cholesterol transport to the liver:
1. HDL assembled in liver and intestine= discoidal HDL containing Apo A-I, Phospholipid (PL), C, and LCAT
2. scavenge cholesterol from cell membranes
3. LCAT activity, esterfies cholesterol to give particle a round shape...forms HDL3
4. HDL exchanged Apoproteins and CE with other Lipoproteins via cholesterol ester transfer protein (CETP)
5. HDL exchanges CE for TG. CE go to VLDL (then IDL) and TG and PL come from VLDL...HDL2 formed

SR-B1= class B Scavenger Receptor B1, HDL receptor, dual role:
-In liver: binds HDL via Apo A-1 and mediates CE uptake
-In other tissues: mediates acceptance of C from the cells

Front 8

Receptors involved in cholesterol transport
-LDL receptor
-LRP
-SR-B1

Back 8

LDL receptor: binds Apo B-100 and E, uptake of LDL and remnants (IDL, CR)

LRP: LDL receptor related protein, hepatic uptake of remnant proteins

SR-B1: Scavenger Receptor, hepatic uptake of CE from HDL in reverse C transport

Front 9

Enzymes involved in cholesterol transport

-LPL
-HL
-PL (shmeh)
-LCAT
-CETP
-ACAT
-MTP

Back 9

LPL: lipoprotein lipase, attached to capillaries in muscle and adipose, hydrolyzes TG in VLDL and chylomicrons to generate FFA for oxidation (muscle) or storage (adipose)
-requires PL and Apo C-II as cofactors
-activated by CII
-inhibited by A-II and C-III

HL: hepatic lipase, attached to liver cells or released by heparin, involved in metabolism of CM remnants and HDL, hydrolyzes lipoprotein TAG and PL

PL: Pancreatic Lipase, Digests TCA in stomach and intestine, makes 2-monoacylglycerols and FFA (similar function to LPL)

LCAT: Lecithin:Cholesterol AcylTransferase, activated by Apo A-I, transfer of FA from lecitin (phosphatidylcholine) to free cholesterol in **HDL

-Cholesteryl Ester Transferase (CETP): exchange of CE for TG b/t HDL and VLDL, associated with HDL, in plasma, transfers CE from HDL to VLDL, IDL, and LDL

Acyl-CoA:Cholesterol Acyltransferase (ACAT): IN CELLS, catalyzes conversion of free cholesterol to CE for storage

Microsomal TG Transfer Protein (MTP): binds TG to Apo B

Front 10

Overflow pathway in cholesterol transport

Back 10

LDL made from VLDL remnants (IDL) deliver cholesterol to peripheral tissues
-extra cholesterol transported back to liver in HDL

-LDL can enter arterial wall on its way back to the liver

Front 11

Why cholesterol requires lipoproteins for transport
-2 reasons

Back 11

Cholesterol requires lipoprotein transport because:
-cholesterol has very low solubility
-cholesterol cannot bind to serum albumin during transportation b/t tissues
-transported in lipoproteins in either free or esterfied form