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Cholesterol
Sanford
36
Biology
Professional
09/18/2008

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Term
How do you regulate Cholesterol synthesis?
Definition
  • regulate HMG-CoA reductase
  • (-)Statin Drugs lower cholesterol
  • (-)Bile acids allosteric inhibitor

↓ATP=↑AMP→ (-)AMP-activate kinase (short term regulation)

Term
What are the primary and secondary bile acids? What are they conjugated with?
Definition

Primary:

-Cholic Acid (31%)

-Chendeoxycholic Acid (45%)

Secondary

-Deoxycholic Acid

-Lithocholic Acid

 

They are all conjugated with Glycine and Taurine

Term
What enzyme breaks down cholesterol? What are it's cofactors?
Definition
  • 7α-hydroxylase
  • NADPH
  • O2
  • Vitamin C
Term
How do you regulate bile synthesis(cholesterol degradation)?
Definition
  • Regulate 7α-hydroxylase
  • (+)live Cholesterol
  • (-)Bile Acids
  • (-)SHP-1 which is induced by FXR when bound to bile acids
  • Thyroid hormone, insulin, glucagon, and glucocorticoids also regulate expression.
Term
Describe the Enterohepatic Circulation of Bile Acids:
Definition
  • 0.3-0.5g/day of cholesterol are taken in by the liver from the blood and converted to primary bile acids.
  • 15/30g of primary bile acids are secreted to the small intestine through the Common Bile Duct.
  • Primary bile acids are reduced/deconjugated →secondary bile acids.
  • 0.3-0.5g are excreted as fecal matter
  • 15/30g are reabsorbed through the Portal Veinand re-conjugated.
Term
What are the symptoms of Gallstones?
Definition
  • sometimes NONE
  • nausea
  • Intense, steady ache in upper middle or upper right abdomen.
  • Sometime pain can be severe and intermettent(come in phases)
  • Can obstruct the bile ducts and lead to severe of life-threatening infection of the bile ducts, pancreas, or liver.
Term
What percentage of Americans are affected by Gallstones?
Definition
1/12
Term
What are the types of Gallstones?
Definition

Cholesterol stones: When the bile contains too much cholesterol/bilirubin and not enough biles salts. Or when the gallbladder doesn't empty as it should.

-Cholesterol in the blood have no relation to the cholesterol in the bile.

-Cholesterol-lowering drugs don't help prevent the stones.

Pigment stones: tend to develop in people who have Cirrhosis, Biliary tract infections, and Hereditary Blood Disorders such as sickle cell anemia. 

Term
Treatments of Gallstones:
Definition
  • surgical removal of gall bladder. (cholecystectomy)
  • oral intake of bile acids (chenodeoxycholic acid and ursodeoxycholic acid)
  • direct perfusion of of gallbladder with organic solvents. (meth t-butyl ether)
  • fragmentation by lithotripsy (involves ultrasound and waves)
Term
What are Lipoproteins? What are the different types?
Definition
  • Phospholipid monolayer surrounding Triacylglycerides and Cholesterol Esters. Also has Apoproteins on surface.
  • Chylomicrons
  • VLDL
  • LDL
  • HDL
Term
How will the different lipoproteins show up on electrophoresi
Definition

(-)Chylomicrons---LDL(β)---VLDL(Pre-β)---HDL(α)(+)

 

Lp(a) give the same band as VLDL(Pre-β)

Term

Describe the properties of plasma lipoproteins:

Definition

Chylomicron: Dietary TAG is major core lipid. ApoB-48, C, E. Delivers lipids by getting hydrolized by lipoprotein lipase.

Chylomicron remnant: Dietary CE is major core lipid. ApoB-48, E. Delivers lipids to Liver by receptor mediated endocytosis.

VLDL: Endegenous TAG. B-100, C, E. Hydrolysis by lipoprotein lypase.

IDL: Endegenous CE. B-100, E. Receptor mediated endocytosis by liverand conversion to LDL.

LDL: Endegenous CE. B-100. Receptor mediated endocytosis by liver and other tissues.

HDL: Endegenous CE. A. Transfer of cholesterol esters to IDL and LDL.

 

Term
What are the different Apolipoproteins? What lipoprotein are they associated with? What is their functions(if known)?
Definition
  • ApoA-1: HDL. Activate LCAT; interacts with ABD transporter.
  • ApoB-48: Chylomicrons. (Unknown Function)
  • ApoB-100: VLDL, LDL. Bind to LDL receptors.
  • ApoC-II: Chylomicrons, VLDL, HDL. Activates lipoproteins lipase.
  • ApoE: Chylomicrons, VLDL, HDL. Triggers clearance of VLDL and chylomicron remnants.
Term
Lipoprotein lipase
Definition
  • Located outside the Liver. Adheres to heparin sulfate on the surface of endothelial cells of blood capillaries.
  • Hydrolyzes TAG of chylomicrons and VLDL, on carbon 1 and 2.
  • Heart lipase is always active, even during a fast. Unlike Adipose lipase.
Term
Hepatic Lipase
Definition
  • Anchored on the surface of liver cells by heparin sulfate.
  • Necessary to convert VLDL remnants(IDL) to HDL.
Term
β-VLDL
Definition
  • VLDL or Chylomicron remnants that have defective ApoE.
  • Migrate as a broad β-band in Type III Hyperproteinemia.(Hyperlipidemia)
  • Intestinal β-VLDL (Chylo remnants), Apo-B48 and Apo-E
  • Hepatic β-VLDL (VLDL remnants), Apo-B100 and Apo-E
  • Risk factor for heart disease
Term
Lipoprotein(a)
Definition
  • Complex of apoprotein(a) and LDL
  • Apoprotein(a) homologous to plasminogen.
  • Elevated levels increase risk of heart disease.
Term
What are the 4 proteins involved in the transfer of cholesterol by HDL?
Definition
  • ABC1
  • LCAT
  • CETP
  • SR-B1
Term
ABC1
Definition

ATP-Binding cassette protein-1

A cell membrane protein that binds HDL (through either apoA-1 or apoE) and pumps free cholesterol from the cell into HDL.

Term
LCAT
Definition

Lecithin-cholesterol acyl transferase

  • Soluble enzyme that associates with HDL in circulation.
  • Activated by Apo1
  • Changes the free cholesterol in HDL into Cholestero Esters.
Term
CETP
Definition

Cholesterol ester transferase protein

  • Transfers cholesterol esters from HDL to other lipoproteins, either alone or in exchange for TAG.
Term
SR-B1
Definition

Scavenger receptor classB type1

  • Membrane protein that facilitates the direct transfer of cholesterol esters HDL to liver during lypolysis of HDL by HL.
Term
What activities increase HDL?
Definition
  • Exercise
  • Loss of body fat
  • Estrogen therapy
  • Moderate alchohol consumption.
Term
What is the major difference between hyperlipidemia IIa and IIb?
Definition

IIa: does not see an increase in Triglycerides.

 

IIb: increase in Triglycerides.

Term
Familial Hypercholesterolemia (FH)
Definition

hyperlipidemia type IIa

  •  Homozygotes are much worse off than heterozygotes.
  • xanthomas: cholesterol deposits on tendons
Term
Describe what blood samples of the different types of Hyperlipidemia would look like?
Definition
  • I: The top half would be cloudy with TAG. The bottom would look fairly normal.
  • IIa: would look normal.
  • IIb: creamy/cloudy because of TAG
  • III: creamy/cloudy because of TAG
Term
Combined Hyperlipidemia of Metabolic Syndrome
Definition
  • A group of matabolic risk factors is seen in one person.
  • High Blood Pressure
  • Abdominal Obesity
  • Atherogenic dyslipidemia
  • Insulin resistance or glucose tolerance
  • Prothrombotic state
  • Proinflammatory state
Term

What causes high LDL cholesterol levels?

Definition
  • Overweight
  • Heredity
  • Diet
  • Physical Activity
  • Age
Term
What are the optimal levels of LDL, HDL, Total Cholesterol, and TAG.
Definition
  • LDL <100
  • HDL 50ish
  • Total cholesterol <200
  • TAG <150
Term
Arteriosclerosis
Definition
  • Vascular changes characterized by thickening and loss of elasticity of arterial walls.
  • Similiar changes to arterioles are know as Arteriolosclerosis.
Term
Atherosclerosis
Definition
  • A subset of arteriosclerosis
  • A disease of large and medium-sized arteries that result in the progressive accumulation within the intima of smooth muscle cells and lipids.
Term
What are the 12 risk factors for heart disease?
Definition
  1. High cholesterol
  2. High blood pressure
  3. Smoking
  4. Sedentary lifestyle
  5. Obesity
  6. Diabetes
  7. Age
  8. Gender(Males more likely)
  9. Family history
  10. Race
  11. Stress/Type A personality
  12. Hemostatic Factors(Clotting)
Term
What are the benefits of Statins and what are the side effects?
Definition

Benefits: Decrease LDL, Slightly raise HDL

 

Side effects: Constipation, nausea, diarrhea, stomach pain, cramps, muscle soreness, pain and weakness, possible interaction with grapefruit juice.

Term
What are the benefits of Colestid, Questran, and Welchol? What are the side effects?
Definition
  • Bile acid binding resins
  • Decrease LDL(works fast)
  • Bloating, constipation, nausea, gas, may increase TAG.
Term

Function of HDL:

Definition
  • Remove cholesterol from cells.
Term
What is the primary target for cholesterol reducing therapy?
Definition
LDL
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