Cholesterol Regulation

Question 1

how does free cholesterol affect cholesterol synthesis?

Answer 1

reduces it 2 ways

1. prevents transcription of HMG CoA reductase
2. prevents uptake into cells via LDL R

Question 2

describe generally 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.

SREBP 1- two subtypes depending on splicing
fatty acid synthesis
1 gene

SREBP2- one subtype
different gene
cholesterol metabolism

Question 3

describe activation of SREBP2

Answer 3

found in the rough ER membrane bound. high levels of cholesterol keep it bound. low levels cause SREPB to translocate into the golgi, where 2 proteases can cleave it free, allowing it to bind to SRE

Question 4

describe what SCAP does

Answer 4

interacts w/ 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 SREBP bound. low cholesterol levels change the conformation of SCAP so that Insig cannot bind, allowing SREBP to move to the golgi

Question 5

what is the major regulator of SREBP1?

Answer 5

this is in the fatty acid synthesis pathway and has a similar inactive form to SREBP2 (membrane bound). however, it is freed by cleavage caused by insulin

Question 6

what 3 things are required in order for the FAS promotor to respond to insulin/glucagon?

Answer 6

e-box
SRE
Sp-1 (transcription factor)

Question 7

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

Answer 7

ATP citrate lyase
acetyl-CoA carboxylase
fatty acid synthase

all under genetic regulation

only ACC does short term regulation

Question 8

how does SREBP1 bind to the SRE?

Answer 8

as a homodimer

Question 9

describe the role of CHREBP

Answer 9

important for the activation of fatty acid synthase- sense 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 promotor, upregulating it

Question 10

AIDS lypodystrophy Syndrome

Answer 10

HIV drug also acts as an inhibitor of SREBP1 breakdown, causing accumulation of fat in 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