Cholesterol Regulation

Question 1

how does free cholesterol effect cholesterol synthesis?

Answer 1

it reduces it in two ways: 1) it prevents transcription of HMG CoA reductase and 2) prevents uptake into cells via LDLR

Question 2

describe the 2 classes of SREBP

Answer 2

cholesterol synthesis is determined by HMG CoA reductase, whose gene expression is controlled by SRE transcription factors that bind to SRE are SREBPs

SREBP1 has 2 subtypes depending on the splicing of FA synthesis 1 gene

SREBP2 one subtype different gene cholesterol metabolism

Question 3

describe the activation of SREBP2

Answer 3

found in the RER and is membrane bound, high levels of cholesterol keep it bound, low levels cause SREPB to translocate to the golgi where two proteases can cleave it and let it bind to SRE

Question 4

what does SCAP do?

Answer 4

it interacts with SREBP in the membrane of the ER, SCAP has a sterol-sensing domain that under the conditions of high cholesterol, binds a protein called Insig, which keeps the SREBP bound, low cholesterol levels change the conformation of the SCAP so that Insig cannot bind, allowing SREBP to move into the golgi

Question 5

what is the major regulator of SREBP1?

Answer 5

this is the FA synthesis pathway and has a similar inactive form to SREBP2 (membrane bound) however it is freed by cleavage which is caused by insulin

Question 6

what are 3 things required in order for the FAS promoter to respond to insulin and glucago?

Answer 6

e-box SRE sp-1 (transcription factor)

Question 7

what are 3 enzymes responsible for taking citrate to palmitate in fatty acid synthesis? which ones are under genetic regulation and which are under short term regulation?

Answer 7

ATP Citrate Lyase, Acetyl-CoA Carboxylase, Fatty Acid Synthase are all under genetic regulation but only ACC is under short term regulation

Question 8

describe the role of CHREBP

Answer 8

this is important for the activation of the fatty acid synthesis as it senses the presence of sugar. CHREBP is present in the cytosol and is activated (dephosphorylated) by glycolytic metabolites where it goes and binds to the E-box on the FAS promoter, thus upregulating it

Question 9

how does SREBP1 bind to the SRE?

Answer 9

as a homodimer

Question 10

what is AIDS lipodystrophy syndrome?

Answer 10

HIV drug acts as an inhibitor of SREBP1 breakdown causing accumulation in the fat of the trunk

Question 11

how does miRNA help SREBP1?

Answer 11

one of its own spliced introns acts as an miRNA that stabilizes the mRNA