| Question |
Answer |
| 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 |