Cholesterol Metabolism 1 Flashcards
(38 cards)
What 3 big classes of biologically active compounds is cholesterol a precursor to?
- Bile Acid
- Steroid Hormones
- Vitamin D
T or F: Cholesterol is an essential component of mammilian membranes.
True
What are the 3 major sources of cholesterol that is sent to the small intestine?
- What are the relative amounts
Food (meat, eggs, dairy)
- 300-500 mg/day
Bililary Cholesterol **Greatest contributor
- 800-1200 mg/day
Intestinal Epithelial Turnover
- 300 mg/day
How much of the cholesterol that’s in the small intestine is actually absorbed?
70%
Why does diet have a smaller affect on serum cholesterol than what people might think.
~1g (1000mg) of NEW cholesterol is synthesized de novo every day by the LIVER and the amount you ingest is only about 1/6 of total cholesterol
What makes cholesterol polar?
Hydroxyl at 3 position
T or F: 40% of circulating cholesterol is esterified to fatty acids.
False, its more like 70%
Where are the following located in lipoproteins and why?
- Free Cholesterol
- Cholesterol Esters
Free cholesterol stays on surface
Cholesterol Esters are more non-polar so they must go to the hydrophobic core
What causes sitosterolemia?
- Symptoms
- ABCG5 and ABCG8 gatekeeper is not there to move sterols out of the cell
- *this is a heterodimer so mutations in either gene = complete loss of function in protein
- Patients have elevated levels of STEROL in the blood, a plant cholesterol that is normally transported out by ABCG5/ABCG8
What does ABC in ABCG5 stand for?
- ATP-binding Cassette Transporter
Where is ABCG5/ABCG8 expressed (2 places)?
- Enterocyte Microvillus Membrane
- Hepatocyte Canalicular Membrane
* This is responsible for making Cholesterol gets in the bile
What does ABCG5/ABCG8 do?
SECRETES cholesterol and plant sterols back into the interstinal lumen and excludes plant sterols from absorption (gatekeeper)
What is Niemann-Pick C1-Like Protein 1 (NPC1L1)?
- Location?
- Located on lumenal side of enterocyte to import cholesterol
- Found in the Highest Density in Brush Border of proximal Jejunum
What drug acts on NPC1L1 and why does it work?
Ezetimibe (Zetia)
- If cholesterol is not reabsorbed (job of NPC1L1) then it must be resynthesized
How can dietary plant sterols and stanols like Benecol inhibit cholesterol absorption and lower plasma cholesterol?
- These cholesterol-like molecules probably displace cholesterol from micelles
What organs do cholesterol synthesis?
- which is the major site of production?
- Liver (Major site)
- Small Intestine, adrenal cortex, gonads
T or F: acetyl CoA is the initial substrate and source of all 27 carbons
True
Where can the cell go to get Acetyl coA for all 27 carbons needed in cholesterol Synthesis?
- Long-Chain Fatty Acid ß-oxidation
- Dehydrogenation of Pyruvate
- Oxidation of Ketogenic Amino acids
What are the requirements to make Cholesterol?
- 18 moles of acetyl CoA
- 36 moles of ATP
- 16 mols of NADPH
**Its costly to make Cholesterol
What is the enzyme of the rate limiting, COMMITTED step of mevalonic acid production?
HMG CoA Reductase
PRINCIPAL SITE OF REGULATION FOR CHOESTEROL SYNTHESIS**
T or F: statins act by inhibiting HMG CoA reductase
True
What reaction does HMG CoA Reductase Catalyze?
HMG-CoA + 2NADPH + 2H+ —-> 2NADP + CoASH + Mevalonate
What transcriptionally regulates HMG CoA?
- factors influencing activity?
Transciptional Regulation - SREBP
Factors influencing activity:
- Intracellular Concentration of: HMG CoA, FREE Cholesterol
- Homones: (+) insulin (+) Thyroid Hormone (-) Glucagon (-) Cortisol
***Note: Hormones work by Changing Phosphorylation State
How does the liver store cholesterol?
- As Cholesterol Esters
