Block 3: Cholesterol Biosynthesis, homeostasis, derivatives

Question 1

describe which nobel prizes and which category have been awarded for cholesterol?

years?

Question 2

Identify the major steps in cholesterol biosynthesis
reactants?
what is the structure of cholesterol?
how is cholesterol stored and transported?
what 2 enzymes are responsible for this?
where are the enzymes located for cholesterol synthesis?
where are the key enzymes?

Question 3

describe stage 1 of cholesterol synthesis?
how is it that we start with acetylcoa?
regulated step?
describe the funcitonal groups that change?

Question 4

describe stage 2
how many different combinations?
how is lanosterol made?
how is cholesterol made from lanosterol?
what is lanosterol impt for?

Question 5

what are 3 sources of acetylcoa for cholesterol synthesis?​where are the enzymes for stage 3?

Question 6

Describe the major physiological roles of cholesterol

and related isoprenoids and sterols

Question 7

Explain the mechanisms involved in regulation of HMG-CoA reductase
short term?
long term?
which is primarily used?
where do statins fit in?

Question 8

Describe the molecular mechanisms by which SREBP

regulates HMG-CoA reductase

• What happens in ER?
• what happes in golgi?
• what is the cholesterol sensor?
• what is the chaperone protein?
• what transports the complex to the gogli?
• what does SREBP bind in the nucleus?
• how is HMGcoareductase regulated post transcirptionally?
• what molecule is common to regulation both transcriptioanlly and post transcriptionally ?
• why are sterols invovled in posttranscriptional regulation

Question 9

how do circadian rhyms regulate cholesterol synthesis?
when does it peak?
how does this related to when to take statin meds?

Question 10

Identify the molecular targets for the diseases related to defects in cholesterol biosynthesis and explain the importance of cholesterol in embryogenesis and development

• common features btwn cholesterol disorders?
• SLOS? transmission? cause? s/s? frequence?

Question 11

Describe the covalent modification of hedgehog with cholesterol?
where is Hh autocleaved?
what is the imporance of cholesterol?
palmitoyl? which end?

Question 12

Describe the general features of exogenous (dietary)

and endogenous cholesterol transport.

• what is essentially the difference?
• how is this different than with TAGs?
• how is LDL receptors in liver regulated?

Question 13

Explain the mechanism by which LDL and LDL receptors

are involved in the endogenous cholesterol transport

• what transports cholesterol to peripheral tissues?
• what is the ligand in LDL receptors?

Question 14

describe regulation of LDL receptors?
what are 2 other things that regulate it?
when cholesterol levels are low, what happens?
when cholesterol levels are high, what happens ?
how does this affect statin treatment?

Question 15

what is neimann pick type II disease

Question 16

Describe the importance of HDL and

the concept of “reverse cholesterol transport”
-how are the two ABC transporters different?

Question 17

what are the 3 ways to regulate cellular levels of cholestero homeostasis?

Question 18

difference between polygenic and familial hypercholesterimia?
what are s/s of both? (serum levels)
which is more common?
how is homozyg different than heterozygote?
what are the 4 classes of FH?
what is one cause of FH that she went into detail about?

Question 19

what are treatments for hypercholeserolemia?
-bile acid sequestrants?what makes it more effective and why?
how do statins work?

what are the 4 major satin groups for treatment? 
what is a new class of cholesterol absorption inhibitors ? what receptor does it work at?

Question 20

identify the connection btsn oxidized LDLscavenger receptors and atherosclerosis