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Flashcards in Lipoproteins Deck (45):


-released by intestinal mucosal cells (into lymph: thoracic duct-->L brachiocephalic vein)
-TAGs resynthesized from 2-MAGs
-ApoB48 (RNA editing, C-deaminase)
-Cholestoryl Esters
-Lipid soluble vitamins
-Remnants (after TAGs removed) absorbed by liver
-dietary lipids
-float on top of blood sample, not present in fasting blood
-90% TAGs, 2% protein, 3% phospholipid, 5% cholesterol and CE (highester % of TAGs in lipoproteins, major source of TAGs in blood with VLDLs)
-ApoCII (recieved from HDLs, also tranfered back)-activates LPL
-ApoE (recieved from HDLs)-necessary for CM remnant uptake by liver



-formed and released by liver with products of de novo fatty acid and cholesterol synthesis following carbohydrate rich meal
-for storage or use
-60% TAG, 20% cholesterol and CE, 15% phospholipids, 5% protein (major source of TAGs in blood with chylomicrons)
-ApoB100 for release into blood
-ApoCII (recieved from HDLs, also transfered back)-activates LPL
-ApoE (recieved from HDLs)-necessary for IDL uptake by liver
-also called pre-β lipoproteins



-VLDLs after TAGs are removed by lipoprotein lipase (via IDLs)
-50% Cholestrol and CE, 22% phospholipids, 8% TAGs, 20% protein (highest % of Cholesterol and CE)
-Normal serum LDL <200 mg/dL (or 180), LDL-C is 100-130 mg/dL, increase with age
-have ApoB100
-70% taken up by liver, 30% to extrahepatic tissues
-t1/2=4 days
-LDL-B is most dense and small (more easily penetrate endothelium, risk factor for CHD)
-LDL-A is less dense
-also called β-lipoproteins



-transport cholesterols from tissues to liver (reverse cholesterol transport)
-40% protein, 30% phospholipid, 25% Cholesterol and CE, 5% TAGs (HDL-2 specifically, highest in protein)
-Resevoir of Apolipoproteins (ApoA1* (70%, for reverse cholesterol transport), ApoCII+ApoE 30%)
-Normal levels b/w 50-70 mg/dL
-higher in females than males, increases with exercise
-risk factor: males: 3 > 2 >1 (size is opposite)
-also called α-lipoproteins
-Potential anti-atherogenic properties
-CEs formed by LCAT activated by ApoA-1, also need free cholesterol ABC-transporter and CETB (reverse cholesterol transport)
-Paraoxonase and PAF acetylhydrolase-reduce LDL oxidation
-Plaque stabilization properties (reduce plaque lipid content, reduce macrophage content, increase plaque smooth muscle content and prevent rupture)
-HDL2 delivers cholesteryl esters to liver or steriodogenic tissue via SR-B1


Normal Fasting blood TAG level

100-150 mg/dL


Lipoprotein Lipase

-cleaves TAGs in lipoproteins to 2 FA and MAG (last fatty acid is eventually cleaved as well, free glycerol taken up by hepatocytes, Fatty acids used for β-oxidation or storage as TAGs)
-anchored in place in capillaries (by heparan sulfate) mostly in heart and adipose (and skeletal muscle)
-Activated by ApoCII (in VLDLs and CMs high % of TAGs, recieved from HDLs)
-synthesized mainly by heart and adipose, N-glycosylated, bound to luninal surfatce of vascular endothelium
-(active as dimer)
-heart isozyme has low Km
-fat isozyme is activated by insulin (high blood glucose), also high Km (faster)


CM remnants

-still contain dietary lipids, lipid soluble vitamins, CEs
-taken up by liver as source of cholesterol
-ApoE, ApoB48



-found in CMs, needed for release from mucosal cells
-Also for receptor recognition of CM remnants



-Found in VLDLs for relase into blood
-If oxidized LDLs cannot be taken up normally and are phagocytized by macrophages-->foam cells
-Required for LDL-receptor



-activates LPL
-found in VLDLs and CMs (high % of TAGs, received from HDLs)
-Given back to HDLs as well



-found on (HDLs), VLDLs, CMs, IDLs, CM remnants, LDLs
-Donated to VLDLs by HDLs
-used for uptake of IDLs and CM remnants by liver
-In general needed for remnant receptors
-Used by LRP for recognition of IDLs
-Different alleles: ApoE-3 most common (75%), ApoE-2 (10%) has poor binding to remnant receptor



-should have ApoB100, ApoCII (this is when they start loosing it, probably very little still have it), ApoE (used for uptake by liver)
-50% taken up by liver
-50% further broken down to LDLs



-Hepatic Lipase (acting on TAGs) (also has phospholipase activity)
-Cleaves TAGs in IDLs, similiar to LDL
-Bound via Heparan sulfate in hepatic capillaires


LDL receptors

-expressed in many (all?-->all cells need cholesterol for membranes) tissues including liver and macrophages
-used for uptake of LDLs (and IDLs in liver)
-recognizes ApoB100
-Down-regulated in liver following cholesterol rich meal: high CM remnants (high cholesterol)--|LDL receptor-->increased serum LDL
-down regulated in extrahepatic tissues when cells have sufficient cholesterol
-do not regonized oxLDLs
-LDL-receptor-related protein (LRP) (said something about taking up IDLs in liver)
-can be recycled, also use catherin to form endosomes (endocytosis)


Some oxidizing agents and antioxidents

oxidants: O2-⋅, NO⋅, H2O2
antioxidents: Vit E, Vit C (ascorbic acid), β-carotene



-low affinity (high Km), nonspecific, nonregulated scavenger receptor on macrophages
-macrophages use to phagocitize oxidized LDLs (oxLDL) (I guess it's able to bind to the oxidized ApoB100 or something)
-macrophage has generally downregulated its LDL receptor when this is being used


Foam cell

-a macrophage (or smooth muscle cell) that has consumed too many oxLDLs
-is large, has irregular membrane, and many lipid droplets
-releases growth factors and cytokines that stimulate migration of smooth muscle (move from media to intima, proliferate, produce collagen, and take up lipid potentially becoming foam cells as well) (fibrofatty atheroma-->atherosclerosis-->potentially MI or stroke or CHD etc)



-Similar to LDL but has unusual structure ("kringles"
-#'s increased by trans-FAs
-#'s lowered by ω-3s and niacin
-Risk factor for CHD



-glycoprotein covalently linked to ApoB100 via disulfide bond
-structural analog to plasminogen (plasmin cleaves fibrin in blood clogs)
-may compete with plasminogen for binding to fibrin-->reduce clot removal-->MI or stroke


CHD risk factors

-total cholesterol:HDL > 5
-high LDL:HDL (LDL-C/HDL-C: >3.5 male, >3 female-PMC article 274394 table 1
-high LDL-B
-Lp(a) may reduce clot removal via Apo(a)


HIgh free cholesterol:

ACAT stores as CE, down regulates HMG-CoA reductase and synthesis of LDL recpetors (SCAP-SREBP retained in ER membrane, cannot enter nucleus)



-activates Lecithin (phosphotidyl choline):cholesterol acyltransferase (LCAT or PCAT)
-synthesized in liver (and maybe small intestine)
-found in HDLs (also in CMs with unknown fxn)



-Lecithin:cholesterol acyltransferase (also PCAT b/c PC)
-phosphotidyl choline + free cholesterol--->lysoPC + CE
-needs ApoA1 for activation
-CEs go into HDLs for reverse cholesterol transport
-synthesized by liver, found free in blood throughout body



-disease where there are abnormally high levels of lipoproteins in blood (hypercholesterolemias and hypertriacylglycerolemias)

Aquired HyperTAGs associated with:
-untreated diabetes mellitus
-EtOH abuse
-Oral contraceptives

Aquired Hypercholesterol
-nephrotic syndrome
-obstructive liver disease
-certain drugs



-abnormally high levels of CMs and VLDLs (high TAG)
-often reduced LPL activity or defective ApoCII or increased release of VLDL
-Normal TAG is <160 mg/dL but increases with age

Aquired HyperTAGs associated with:
-untreated diabetes mellitus
-EtOH abuse
-Oral contraceptives



-high levels of LDLs and remnants (i.e.: CM remnants) (high cholesterol and CEs)
-often defective LDL-receptors or ApoE deficiency
-normal total cholesterol <200 mg/dL (inc w/ age)
(total C=LDL-C + HDL-C + VLDL-C, VLDL-C is assumed to be VLDL/5, not necessarily true in obese patients)

Aquired Hypercholesterol
-nephrotic syndrome
-obstructive liver disease
-certain drugs


Type I Hyperlipidemia

Hyperchylomicronemia (rare)
-high levels after 12-14 hr fast
-Type 1a=deficiency of LPL
-Type 1b=deficiency of ApoCII
-Type 1c=presence of LPL inhibitor protein
-childhood onset, abdominal colic
-xanthomas (trunk, buttock, extremities
-blood shows vial lipemic plasma (creamy layer on top with clear infranatant)
-lipemia retinalis, hepatosplenomegaly, irritability, recurrent epigastric pain, inc risk of pancreatitis


Type IIa Hyperlipidemia

Familial Hypercholestrolemia

-High LDL, normal VLDL
-defective LDL-receptor (autosomal dominant)
-heterozygous 1:500 (adult onset, risk of coronary heart disease)
-homozygous 1^-6 (childhood onset, risk of MI, death in childhood)
-xanthoma over tendon and xanthelasmas


Type IIb Hyperlipidemia

Familial combined hyperlipidemia

-high LDL and high VLDL
-onset in puberty 1:100 (pts with CVD are 1:10)
-complex causes, several genes (ApoB100 up?, VLDL up? defective clearance of LDL?)


Type III Hyperlipidemia

Dysbetalipoproteinemia (rare)

-homozygous for ApoE2 (low affinity for receptor) (called β-VLDL)
-high IDL and CM remnants
-total cholesterol similar to Type IIa or IIb
-palmar xanthomas and tubereruptive xanthomas over elbows and knees
-adult onset
-accelerated atherosclerosis


Type IV Hyperlipidemia

Hyperprebetalipoproteinemia (1:100)

-High serum VLDL
-LPL deficiency or overproduction of VLDL
-High serum TAG can lead to pancreatitis


Type V hyperlipidemia

Mixed Hypertriacylglycerolemia

-High VLDL, High CM
-Blood: creamy layer on top and turbid infranatant



Inhibit HMG-CoA Reductase (competitve inhibition)

-down mevalonic acid-->less GPP (prenylation)-->less FPP (prenylation, dilichol, ubiquinone)-->less hepatic cholesterol-->more SREBP-->more LDL receptors-->Less VLDL assembly

-less great: down isoprenylated proteins, less CoQ, less diliochol


Plant stanols and sterols

Displace cholsterol from micelles druing absorpion



blocks transporter protein, reduces cholesterol absorption


Bile sequestering drugs

-bind bile acids/salts in intestine-->less lipid digestion, increased bile content in feces
-block reuptake into liver via portal vein-->liver needs to do de novo cholesterol synthesis for 1º bile acids
-low free cholesterol levels in hepatocyte--> up LDL receptor synthesis-->lower serum LDL



-Inhibit synthesis of ApoC-III (a LPL inhibitor) in hepatocytes
-Lower VLDL concentration in blood via decreased VLDL synthesis and increased LPL
-stimulate Apo A synthesis-->up hepatocytes
(for hyperlipidemia)
-For type II patients



Vitamin (B3), i'm sure it does other stuff too

reduces LDL-cholesterol and TAGs, raises HDL



-plasma membrae free cholesterol ABC-transporter
-transports free cholesterol from plasma membrane into extracellular space


reverse cholesterol transport

-Nacent discoidal HDL formed either in liver and secreted into blood or Apo A-1 released by liver and HDL is formed by addition of phospholipid fragments from other lipoproteins
-discoidal, contains Apo A-1 needed for activation of LCAT
-few if any CEs
-LCAT uses PC from HDL to form CE and lyso-PC
-Phospholipids from other lipoproteins taken up from blood or transfered to HDL3 by specific protein forming HDL2 with more cholestrly esters
-HDL2 delivers cholesteryl esters to liver or steriodogenic tissue via SR-B1
-After bind SR-B1, phospholipid layer is opened by phospholipase activity of hepatic lipase-->CE enters liver-->phospholipid layer closes and is HDL3 again



-HDL2 delivers cholesteryl esters to liver or steriodogenic tissue via SR-B1 (scavenger receptor)



cholesteryl ester transfer protein

-Transfer of TAGs from VLDL to HDL in exchange for CEs
-improves LCAT action (more substrate, less product)



-very low serum HDL (<35 mg/dL)
-aquired is related to obesity, smoking, medical drugs, cholesterol reducing drugs

-Tangier disease: hereditary form, defective cholesterol ABC transporter, low HDL adn coronary heart diseas in childhood


Tangier Disease

-hereditary form of hypoalphalipoproteinemia
-defective cholesterol ABC transporter
-low serum HDL
-coronary heart diseas in childhood
-orange tonsils
-corneal opacities
-enlargement of liver and spleen



-very low serum VLDL and LDL and CMs
-name refers to LDLs, nearly absent
-defect in Microsomal TAG transfer Protein (MTP) which normally interacts with api B in formation/assembly of VLDLs and CMs
-fat malabsorbtion
-TAG accumulation in liver and intestine
-retinis pigmentosa
-peripheral neuropathy