Cholesterol Biosynthesis Flashcards
cholesterol solubility in water
- low solubility in water
cholesterol present in plasma bound to
- lipoproteins
cholesterol esters are located where
- in the interior of lipoproteins
free cholesterol is located where
- on the surface of lipoproteins
cholesterol is a precursor for
- bile acids
- steroid hormones
- vitamin D
result of defects in cholesterol synthesis in mice
- generally lethal
most cholesterol synthesis occurs where?
- in the liver
- 80%
what is cholesterol synthesized from
- HMG CoA in the cytosol
rate limiting step of cholesterol synthesis
- HMG CoA reductase
role of insulin in cholesterol synthesis
- positive regulator of HMG CoA reductase
important intermediates in cholesterol synthesis
- geranyl diphosphate
- farnesyl diphosphate
geranyl diphosphate goes on to to create
- geranylgeranyl disphosphate
geranylgeranyl diphosphate goes on to create
- ubiquinone
- geranylgeranylated proteins (rho)
ubiquionine important for
- oxidative phosphorylation
geranylgeranylated proteins important for
- signal transduction
fernesyl diphosphate goes on to create
- fernesylated proteins (Ras)
- dolichol phosphate
dolichol phosphate important for
- synthesis of complex glycoproteins
HMGCoA reductase expression and activity inhibited by
- oxysterols derived from intracellular free cholesterol
LDL receptors are down regulated by
- free cholesterol
fat and cholesterol are made in what state?
why
- in the fed state
- it takes 18 ATP to make them
mechanisms to control cellular cholesterol levels
- biosynthesis
- uptake
- catabolism & excretion
- storage
uptake
- LDL receptors on liver allow cholesterol to be taken up
storage
- liver stores cholesterol using ACAT
diet high in cholesterol result
- too much cholesterol in cell
- negative feedback on LDL receptors
- more cholesterol in the circulation
diet high in saturated fats
- inhibit storage of cholesterol
- more cholesterol in cell
- down regulation of LDL receptors
- more cholesterol in circulation
result of saturated fatty acids
- reduce membrane fluidity
- reduce clustering and uptake of LDLR
diet low in fiber
- not secreting bile acids out of system
- higher level of cholesterol inside cell
- down regulation of LDL receptors
- up regulation of plasma LDL
primary bile acids are synthesized where
- in the liver
rate limiting step for bile acid synthesis
- 7 alpha hydroxylase
which are the primary bile acids
- cholic and chenodeoxycholic acids
deoxycholic and lithocholic acids are products of
- further metabolism in the intestine
which are the must abundant primary bile acids?
- colic acids
how do we convert bile acids to bile salts?
- add groups to make it more polar
function of bile acids
- emulsify dietary fats for digestion and absorption
- facilitate absorption of fat soluble vitamin
- only significant mechanism for eliminating cholesterol from body
- prevent precipitation of cholesterol out of solution in gall bladder so you don’t get gall stones
7 alpha hydroxylase activated by
- cholesterol
7 alpha hydroxylase inhibited by
- bile acids
importance of enterohepatic circulation of bile acids
- up to 99% of bile acids are reabsorbed, enter the portal circulation, and return to the liver
