Lipoproteins Flashcards
Chylomicrons
Formed in the intestinal mucosal cells.
Transport TAGs (90%), cholesterol esters, fat soluble vitamins, phospholipis, etc.
Released in the lymph (requires apo B-48), then to the blood.
Delivers dietery TAGs to peripheral tissue. Delivers cholesterol to the liver in the form of chylomicron remnants which are mostly depleted of their TAGs
Band at origin on electrophoresis due to lack of proteins
VLDL
Very low density lipoproteins
Produced in the liver
Functions to carry lipids from the liver to peripheral tissues. Lipids are in the form of TAGs
Apo B-100 signals release from the liver
60% TAG, 20% cholesterol plus cholesterol esters
Pre-Beta line on electrophoresis (due to apo b-100, apo C-II and apo E)
LDL
Low density lipoproteins
50% cholesterol esters, 8% TAG
Primary function is the provide cholesterol to the peripheral tissues.
Normal LDL cholesterol serum values are below
180 mg/dL
Beta line on electrophoresis (due to apo b-100
HDL
High Density Lipoproteins
40% Proteins, 25% cholesterol esters, 30% phospholipids
Resivoir for Apo C-II, Apo E
Function to take up cholesterol from peripheral tissues and return it to the liver as cholesterol esters
Normal HDL cholesterol serum levels are 40-70 mg/dL
Risk factor for males below 40, for females below 50 mg/dL
Alpha line on electrophoresis
Lipoprotein Lipase (LPL)
Extracellular enzyme mainly bound to capillary walls of heart, skeletal muscle and
adipose tissue. Anchored to endothelial cells by Heparan Sulfate
Cleaves TAGs inside of lipoproteins, specifically in chylomicronsand VLDL
TAG sare eventually cleaved to free glycerol and three free fatty acids in blood. (LPL itself cleaves TAGs to MAG and 2 fatty acids)
Requires ApoC-II for activation
Heart LPL vs. Adipose Tissue LPL
Heart LPL has smaller Km and therefore has a higher affinity
FA is not stored in the heart, but immediately used for energy.
Adipose LPL is activated by insulin. FA is stored in adipose tissue in the form of TAG
Apo B-48
Synthesized in intestinal mucosal cells and is needed for the release of chylomicrons into the lymph.
The structure of apo B-48 is 48% of apo B-100
(mRNA editing, cytidine deaminase forms a stop codon)
Apo B-100
Synthesized in the liver and is needed for the release of VLDLs into the blood
Liver LDL receptors also recognize Apo B-100 for uptake of LDLs.
Apo B-100 is the largest single polypeptide chain
Apo E
Required for receptor mediated endocytosis of IDL (LDL remnants) and chylomicron remnants.
Donated by HDL
Hepatic Lipase (HTGL)
Cleaves TAG to IDL (similar to Lipoprotein Lipase) in liver capillaries forming LDL.
Apo C-II
Activator of lipoprotein lipase.
Found in HDL and transferred to VLDL and chylomicrons in the blood.
LCAT (PCAT)
Lecitin: cholesterol acyltransferase (phosphatidylcholine)
Esterifies cholesterol taken up by HDL
Synthesized in the liver. binds to HDL and is activated by Apo A-I
SR-A
Scavenger Receptor-A
Found on macrophage cell membranes. Mediate endocytosis of chemically modified LDL.
Cholesteryl esters accumulate in macrophages and cause their transformation into Foam ells which participate in the formation of atherosclerotic plaque.
Risk factors for coronary artery disease
Total cholesterol: HDL >5 High LDL:HDL ratio TAG: HDL ration >4 High levels of LDL-B (more easily trapped and oxidized) Lp(a)
ACAT
Acyl-CoA Cholesterol acyl transferase
at high free cholesterol levels in the cytosol ACAT converts cholesterol to cholesterol esters
Acquired hypertriacylglycerolemias
Associated with: Hypertension Untreated Diabetes Mellitus Alcohol abuse Usage of oral contraceptives Hyperuricemia
Abnormal high levels of lipoproteins that have a high percentage of TAGs (chylomicrons and VLDLs)
[often related to reduced LPL activity or defective apoC-II or to increased release of VLDL]
Acquired hypercholesterolemia
Associated with:
Hypothyroidism
Nephrotic Syndrome
Obstructive Liver Disease
Abnormal high levels of lipoproteins with a high percentage of cholesterol and cholesterylesters
(LDL and lipoprotein remnants)
[often related to defective LDL-receptors or apoE deficiency]
Dyslipidemia Type I
Hyperchylomicronemia
Increased chylomicrons in the blood due to LPL deficiency or altered Apo C-II
Causes pancreatitis, hepatosplenomegaly, eruptive xanthomas
Autosomal recessive
Dyslipidemia Type IIa
Familial Hypercholesterolemia
Increased levels of LDL (normal VLDL) due to absent or decreased LDL receptors.
Causes accelerated atherosclerosis, Tendon Xanthomas, Corneal Arcus
Autosomal Dominant
Dyslipidemia Type IIb
Familial Combined Hyperlipidemia
Increased LDL and VLDL due to complex, not well understood mechanism.
Onset in puberty, Common 1:100
Dyslipidemia Type III
Dysbetalipoproteinemia
High IDL and Chylomicron remnants due to Apo E deficiency
Characterized by palmar xanthomas and tubereruptive xanthomas over the elbows and knees
Rare disorder with Adult onset with accelerated atherosclerosis
Dyslipidemia Type IV
Hyperprebetalipoproteinema
High serum VLDLs
may result from LPL deficiency or overproduction of VLDL. High serum TAG can lead to pancreatitis
Dyslipidemia Type V
Mixed Hypertriacylglycerolemia
High serum VLDL and high chylomicrons
Patients serum: creamy layer of top and turbid infranatant
CEPT
Allows the interchange of choleterol esters for TAGs from HDL2 to VLDL
SR-B1
facilitates the delivery of cholesterol esters from HDL to the liver.
Hypo alpha lipoproteinemia
Very low serum HDL cholesterol below 35 mg/dL
If it is acquired, it is related to obesity, smoking, some medical drugs and also to cholesterol reducing drugs
Tangier disease
Hereditary disease which leads to very low serum HDL and coronary heart disease in childhood
Defective cholesterol ABC transporter in the plasma membrane.
This leads to less substrate for LCAT and early degradation of the lipid poor apoA-1 in blood.
Characterized by coronary artery disease, corneal opacities and orange tonsils, also enlargement of liver and spleen.
Abetalipoproteinemia
Rare disease characterized by very low amounts of serum VLDL, LDL and chylomicrons.
defect in the microsomal TAG transfer protein (MTP) which normally interacts with apoB and is needed for the formation of VLDL or CM
Results in TAG accumulation in liver and intestine,
retinitis pigmentosa and peripheral neuropathy.
