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WVSOM - Biochem

Cholesterol and Bile Acid Synthesis

Cholesterol Synthesis Starting materials Acetyl CoA NADPH ATP
HMG-CoA reductase rate limiting step (target of drug therapy)
Products of cholesterol synthesis Cholesterol NADP+ ADP
Location of Cholesterol synthesis hepatocytes
regulated enzyme of cholesterol synthesis HMG CoA reductase
Increasing levels of cholesterol __________ cholesterol synthesis decreases
HMG CoA is active when dephosphorylated
HMG CoA is dephosphorylated with ___________ insulin to glucagon levels. high
HMG CoA is inactivated by ____________ and is then _____________ Glucagon; phosphorylated
Most significant factor in regulation of cholesterol biosynthesis decreasing HMG CoA reductase synthesis
Proteolysis of HMG CoA reductase increases as ____________ sterol levels rise
Which drug class inhibits this enzyme statins
Extrahepatic cholesterol synthesis occurs under certain pathological conditions
Why is cholesterol esterified regulation
where is cholesterol esterified on lipoprotiens and in cells
How does esterification change regulation cholesterol ester CANNOT regulate HMG CoA reductatse
Two enzymes that esterize cholesterol LCAT (Lecithin) ACAT (acyl CoA)
LCAT Esterifies cholesterol on lipoprotein that can be transferred from HDL to LDL
ACAT esterifies cholesterol within the cell
Extrahepatic cholesterol synthesis under certain pathological conditions
Where are cholesterol esterified/de-esterified in cells? lipoproteins
Esterifcation of cholesterol changes the properties of cholesterol especially with regard to its control functions
LCAT Lecithin: chelesterol acyl transferase Esteerifies cholesterol on lipoproteins
What is transfered to LDL and HDL Esterfied cholesterol
ACAT esterfies cholesterol within the cell
Cholesterol esterase reveses LCAT and ACAT esterification
Bile Salt Synthesis Location hepatocytes
Starting compounds of Bile Salts Cholesterol, ATP, NADPH
4 conjugated bile salts taurocholic glycocholic taurochenocholic glycohenocholic acids
Conjugation of bile salts increases ____________ solubility
Solubility enables bile salts to act as detergents
Conjugated bile salts composed of primary bile salts, cholic acids and chenocholic ascid conjugated to taurine or glycine which are hydrophobic
How much bile salts are recycled > 95%
Liver synthesis of bile acid _____ g/day .2 - .6
Amount of bile salts reabsorbed 12-32 g/day
bile removed by feces .2-.6 g/day
Why would we want to decrease bile salt reabsorption drugs which bind to bile acids prevent their reabsorption to increase cholesterol excretion
Cholesterol esterase reverses LCAT and ACAT by de-esterifying cholesterol
Bile Salt Exrection in feces
Primary Bile Salts chenocholic acid and chlic acid
Location of bile acid synthesis hepatocytes
starting compounds of bile acid synthesis cholesterol ATP NADPH
Controlled step of bile acid salts products and substrate!!!!
Products of bile acid synthesis cholic acid and chenocholic acids
Conjugated bile salts primary bile salts bound to hydrophobic taurine or glycine
4 conjugated bile salts taurocholic glycocholic taurochenocholic glyochenocholic acids
Bile Salts recycled > 95% 12-32 g/day
Why would we want to pharmachologically bind drugs to bile acids to prevent reabsorption to increase cholesterol excretion
Created by: Todd Jamrose Todd Jamrose on 2008-10-17

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