• regulate HMG-CoA reductase
• (-)Statin Drugs lower cholesterol
• (-)Bile acids allosteric inhibitor

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

Primary:

-Cholic Acid (31%)

-Chendeoxycholic Acid (45%)

Secondary

-Deoxycholic Acid

-Lithocholic Acid

They are all conjugated with Glycine and Taurine

• 7α-hydroxylase
• NADPH
• O₂
• Vitamin C

• 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.

• 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.

• 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.

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. 

• 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)

• Phospholipid monolayer surrounding Triacylglycerides and Cholesterol Esters. Also has Apoproteins on surface.
• Chylomicrons
• VLDL
• LDL
• HDL

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

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

Describe the properties of plasma lipoproteins:

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.

• 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.

• 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.

• Anchored on the surface of liver cells by heparin sulfate.
• Necessary to convert VLDL remnants(IDL) to HDL.

• 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

• Complex of apoprotein(a) and LDL
• Apoprotein(a) homologous to plasminogen.
• Elevated levels increase risk of heart disease.

• ABC1
• LCAT
• CETP
• SR-B1

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.

Lecithin-cholesterol acyl transferase

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

Cholesterol ester transferase protein

• Transfers cholesterol esters from HDL to other lipoproteins, either alone or in exchange for TAG.

Scavenger receptor classB type1

• Membrane protein that facilitates the direct transfer of cholesterol esters HDL to liver during lypolysis of HDL by HL.

• Exercise
• Loss of body fat
• Estrogen therapy
• Moderate alchohol consumption.

IIa: does not see an increase in Triglycerides.

IIb: increase in Triglycerides.

hyperlipidemia type IIa

•  Homozygotes are much worse off than heterozygotes.
• xanthomas: cholesterol deposits on tendons

• 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

• 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

What causes high LDL cholesterol levels?

• Overweight
• Heredity
• Diet
• Physical Activity
• Age

• LDL <100
• HDL 50ish
• Total cholesterol <200
• TAG <150

• Vascular changes characterized by thickening and loss of elasticity of arterial walls.
• Similiar changes to arterioles are know as Arteriolosclerosis.

• 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.

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)

Benefits: Decrease LDL, Slightly raise HDL

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

• Bile acid binding resins
• Decrease LDL(works fast)
• Bloating, constipation, nausea, gas, may increase TAG.

Function of HDL:

• Remove cholesterol from cells.