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2.b. Biochemistry II > Lipoproteins > Flashcards

Lipoproteins Flashcards

1
Q

Chylomicrons

A

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

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2
Q

VLDL

A

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)

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3
Q

LDL

A

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

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4
Q

HDL

A

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

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5
Q

Lipoprotein Lipase (LPL)

A

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

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6
Q

Heart LPL vs. Adipose Tissue LPL

A

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

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7
Q

Apo B-48

A

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)

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8
Q

Apo B-100

A

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

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9
Q

Apo E

A

Required for receptor mediated endocytosis of IDL (LDL remnants) and chylomicron remnants.

Donated by HDL

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10
Q

Hepatic Lipase (HTGL)

A

Cleaves TAG to IDL (similar to Lipoprotein Lipase) in liver capillaries forming LDL.

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11
Q

Apo C-II

A

Activator of lipoprotein lipase.

Found in HDL and transferred to VLDL and chylomicrons in the blood.

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12
Q

LCAT (PCAT)

A

Lecitin: cholesterol acyltransferase (phosphatidylcholine)

Esterifies cholesterol taken up by HDL

Synthesized in the liver. binds to HDL and is activated by Apo A-I

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13
Q

SR-A

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.

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14
Q

Risk factors for coronary artery disease

A 
Total cholesterol: HDL >5
High LDL:HDL ratio
TAG: HDL ration >4
High levels of LDL-B (more easily trapped and oxidized)
Lp(a)
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15
Q

ACAT

A

Acyl-CoA Cholesterol acyl transferase

at high free cholesterol levels in the cytosol ACAT converts cholesterol to cholesterol esters

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16
Q

Acquired hypertriacylglycerolemias

A 
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]

17
Q

Acquired hypercholesterolemia

A

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]

18
Q

Dyslipidemia Type I

A

Hyperchylomicronemia

Increased chylomicrons in the blood due to LPL deficiency or altered Apo C-II

Causes pancreatitis, hepatosplenomegaly, eruptive xanthomas

Autosomal recessive

19
Q

Dyslipidemia Type IIa

A

Familial Hypercholesterolemia

Increased levels of LDL (normal VLDL) due to absent or decreased LDL receptors.

Causes accelerated atherosclerosis, Tendon Xanthomas, Corneal Arcus

Autosomal Dominant

20
Q

Dyslipidemia Type IIb

A

Familial Combined Hyperlipidemia

Increased LDL and VLDL due to complex, not well understood mechanism.

Onset in puberty, Common 1:100

21
Q

Dyslipidemia Type III

A

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

22
Q

Dyslipidemia Type IV

A

Hyperprebetalipoproteinema

High serum VLDLs

may result from LPL deficiency or overproduction of VLDL. High serum TAG can lead to pancreatitis

23
Q

Dyslipidemia Type V

A

Mixed Hypertriacylglycerolemia

High serum VLDL and high chylomicrons
Patients serum: creamy layer of top and turbid infranatant

24
Q

CEPT

A

Allows the interchange of choleterol esters for TAGs from HDL2 to VLDL

25
Q

SR-B1

A

facilitates the delivery of cholesterol esters from HDL to the liver.

26
Q

Hypo alpha lipoproteinemia

A

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

27
Q

Tangier disease

A

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.

28
Q

Abetalipoproteinemia

A

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.

2.b. Biochemistry II (17 decks)

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