Cholesterol Flashcards
How does cholesterol effect fatty acid chains?
it inserts itself between fatty acid chains and prevents their crystalisation
what enzyme synthesises cholesterol?
Acetyl Coenzyme A
how is cholesterol transported in the blood?
by low density lipoproteins
what are some importnat derivatives of cholesterol?
bile salts and steroid hormones
all 27 carbon atoms of cholesterol are derived from what molecule?
acetyl CoA
What are the three steps to cholesterol synthesis?
- synthesis of isopentenyl pyrophosphate
- condensation fo 6 molecules of isopentenyl pyrophosphate to form squalene
- squalene cyclizes and the tetracyclic product is converted to cholesterol
whats the normal cholesterol level in adult humans?
140 g
why is a high cholesterol dangerous?
normal levels are essential to life, however deposition in arteries is associated with cardiovascular disease and stroke
regulation of cholesterol biosynthesis is via what system?
it is controlled by a negative feedback mechanism mediated primarily by changes in the amount and activity of 3 hydroxy 3 methylglutaryl CoA reductase
AKA
HMG CoA reductase
which is inhibited by statins
how do we control the rate of synthesis of HMG CoA reductase?
controlled by SREBP (sterol regulatory element binding protein) -
when cholesterol levels are down, this transcription factor induces transcription of HMG CoA reductase
how is rate of HMG CoA reductase translation controlled?
rate of translation is inhibited by nonsterol metabolites derived from mevalonate and dietary cholesterol
how is degredation of HMG CoA reductase controlled?
in response to increasing levels of cholesterol, the enzyme undergoes proteolysis
how can we control phosphorylation of HMG CoA reductase?
phosphorylation decreases the activity of the reductase and occurs in response to low levels of ATP
what is the main site of cholesterol synthesis?
in the liver -
cholesterol in ecess of the liver’s own needs is exported in the blood in what form?
in the form of very low density lipoproteins ( VLDLs)
how do statins work?
statins inhibit the synthesis of HMG CoA reductase in the liver
what pharmacological agent can we give that reduces absorption of exogenous cholesterol?
we can give cholestyramine colestipol - which sequesters bile acids in the intestine and reduces the absorption of exogenous cholesterol and increases the metabolism of endogenous cholesterol into bile acids
what is the purpose of bile salt as it relates to cholesterol?
eliminates cholesterol from the body (cholesterol is a bile salt precursor)
how do we turn bile acids into bile salts?
conjugating bile acids with either glycine or taurine
how can an increased cholesterol lead to gall stones?
not enough bile salts being secreted to handle the amount of cholesterol being secreted
- due to malabsorption of bile acids, biliary tract obstruction, hepatic dysfunction, reduced bile acid synthesis, lack of melatonin-
cholesterol is the precursor to which 5 major classes of steroid hormones?
progestagens, glucocorticoids, mineralocorticoids, androgens and estrogens
what can vitamin D deficiency in children lead to?
rickets - a disease characterised by inadequate calcification of cartilage and bone
