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C6
Knox - lecture notes (chol synth)
23
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Not Applicable
10/22/2007

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Term
What do all carbons in cholesterol come from?
Definition
Acetyl CoA
Term
What are the most important carbon positions in perhydrocyclopenathrene and where are they?
Definition
3, 10, 13, 17
Term
True or false: Sterols have a hydroxyl group at C3 and an alipathic chain o at least 8 C's at C17.
Definition
True
Term
Outline the isoprenoid pathway.
Definition
Acetyl CoA à Mevalonate à Isopentenyl PP/Dimethyl PP à tRNA or Farnesyl PP à Squalene synthase à Cholesterol. From Farnesyl PP, Ubiquinone or Dolichol can also be made.
Term
True or false: 65% of chol in the serum is cholesterol ester ad it is located on the exterior of LP particles?
Definition
False. CE's make up 65% of total chol, but they're carried on the interior. Esterification makes chol more non-polar and serves to trap it within the carrier LP's or intracellular depoits.
Term
What two enzymes form CE's from cholesterol?
Definition
ACAT (in tissue ER) and LCAT (in plasma). End result is the same: a cholesterol with an aceyl group esterified to the 3C.
Term
Where is LCAT synthesized?
Definition
In the liver. It is excreted into the plasma where it acts on substrates in LP's. Main pathway transfers acyl chain from 2 position of PC to chol in HDL.
Term
What hydrolyzes CE's?
Definition
1) pancreatic juice in intestinal lumen, 2) lysosomal enzymes, 3) ER (both synth and breakdown given neutral pH optimum)
Term
True or false: All cells in the body make cholesterol?
Definition
True.
Term
Where does cholesterol eventually go?
Definition
Most is excreted. A lot goes to making steroid hormones, too.
Term
What is sitosterolemia?
Definition
A rare AR disorder where patients hyperabsorb not only cholesterol but also other plant sterols (e.g. sitosterol). Sitosterol is usually pumped back into the intestintal lumen by sterolins on enterocytes. The sterolin gene is defective in these patients.
Term
Why has there only been shown to be a 10-25% drop in chol when patients go on a chol free diet?
Definition
Lots is synthesized de novo.
Term
What are the steps of cholesterol synthesis?
Definition
2 Acetyl CoA (2C) à Acetoacyl CoA (3C) (Thiolase) (+ Acetyl CoA) à *HMG CoA (5C) (HMG CoA synthase) (+ 2 NADPH)à *Mevalonate (HMG CoA Reductase-committed and rate-controlling step) à Isopentyl and dimethyl PP (still 5C) à Ger PP (10C) à Farn PP (15C)à Squalene (Squalene synthase) à Lanosterol à à à Cholesterol
Term
What component of the cholesterol synthesis pathway needs to be carried?
Definition
Squalene by squalene carrier protein. "Carry squalene baby."
Term
Where else is HMG CoA synthesized?
Definition
In cholesterol synthesis, HMG CoA is made in the cytosol to make mevalonate and eventually cholesterol. HMG CoA is also synthesized in the mitochondrion for the production of acetoacetate (KB synthesis).
Term
True or false: HMG CoA reductase, squalene synthetase, and all the enzymes that convert squalene to chol are in the ER?
Definition
True.
Term
Name four major bile acids in humans? How do they differ?
Definition
Bile acids differ in the number and position of hydroxyl groups. Some examples are cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. (All have "cholic" in them.)
Term
What does it mean if a bile acid is conjugated?
Definition
Amide linkage at C25 with either glycine or taurine.
Term
What is the difference between primary and secondary bile acids?
Definition
Cholic acid and chenodeoxycholic acid (the C's) are primary and synthesized in the liver from cholesterol. The secondary bile acids (deoxycholic acid and lithocholic acid) are formed in the intestine by bacteria that remove hydroxy groups and any conjugated glycine or taurine.
Term
What are gallstones?
Definition
Cholesterol rich bile that builds up in gallbladder in crystals then gets caught in mucin gel.
Term
What vitamin is synthesized from cholesterol?
Definition
Vitamin D3. Remember it needs light to open it's ring and then must be processed by kidney and liver.
Term
What four things should we know about hormones?
Definition
1) Everything starts from cholesterol. 2) Cholesterol is converted to various steroid hormones via branched pathways. 3) Hydroxyl groups are added, some are oxidized to ketones, and some carbons are lost in successive transformations. 4) Congenital adrenal hyperplasias result from specific enzyme defects.
Term
What enzyme converts cholesterol to Pregnenolone?
Definition
Desmolase. It does so with NADPH and O2. 27C à 21C.
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