MCP 1

Question 1

structure of cholesterol

Answer 1

4 planar hydrocarbon rings called the steroid nucleus. Other groups attached to this 4 ring structure.

Question 2

what do sterols do in the cell membrane?

Answer 2

increases the packing within the hydrophobic core of the bilayer, thereby increasing mechanical strength while decreasing permeability and fluidity

Question 3

sitosterolemia

Answer 3

rare inherited plant sterol storage disease. caused by mutations of ABCG5 and ABCG8 genes which encode ABC transporters sterolin 1 and 2. diminished pumping of plant sterols back into intestine. increased phytosterols in blood and tissue. premature coronary atherosclerosis.

Question 4

basics of cholesterol synth

Answer 4

made by all cells except RBCs. majority made in liver, intestines, adrenal cortex, and reproductive tissue. carbons provided by Acetyl coA. requires energy from hydrolysis of acetyl CoA and ATP. occurs on cytoplasmic surface of smooth ER

Question 5

acetyl CoA –> HMG CoA

Answer 5

2 molecules of acetyl CoA condense to make acetoacetyl CoA. A third molecule of acetyl CoA is added by HMG CoA synthase forming HMG CoA. Cytosolic form of HMG CoA synthase does this reaction

Question 6

regulatory step of cholesterol synthesis

Answer 6

HMG CoA to Mevalonate. Done by HMG CoA reductase. this enzyme is an integral membrane protein of the smooth ER. Inhibition by excess cholesterol

Question 7

8 steps of mevalonate –> cholesterol

Answer 7

1. Mevalonate + 2ATP -> 5-pyrophosphomevalonate
2. 5-PPM + ATP -> IPP (5 carbons)
3. IPP -> DPP (isomerization)
4. IPP + DPP -> GPP (10 carbons)
5. GPP + IPP -> FPP (15 carbons)
6. FPP + FPP -> squalene (30 carbons)
7. Squalene -> lanosterol (ring closure)
8. lanosterol -> cholesterol (multi-step process)

Question 8

how many ATP needed to make squalene?

Answer 8

18

Question 9

SLOS (smith lemli opitz syndrome)

Answer 9

autosomal recessive disorder of cholesterol biosynth. partial deficiency in an enzyme that reduces double bond in 7-DHC, converting it to cholesterol

Question 10

gene expression regulation of HMG CoA Reductase

Answer 10

when cholesterol is low, SREBP-SCAP moves to golgi where SREBP is cleaved, allowing it to act as a transcription factor for gene SRE.

Cholesterol binds SCAP, which makes it bind to other ER proteins preventing SREBP-SCAP from moving and being cleaved

Question 11

enzyme degradation regulation of HMG CoA Reductase

Answer 11

cholesterol binds sterol sensing domain of the enzyme itself. this causes reductase to bind to ER and be ubiquitinated and degraded

Question 12

phosphorylation/dephosph regulation of HMG CoA Reductase

Answer 12

High AMP, low ATP = phosphorylated enzyme and low cholesterol synth.

dephosph = activated enzyme

Question 13

hormonal regulation of HMG CoA Reductase

Answer 13

insulin and thyroxine upregulate, glucagon and glucocorticoids downregulate

Question 14

statin drugs

Answer 14

structural analogs of HMG. competitive inhibitors of HMG CoA Reductase

Question 15

bile acid structure

Answer 15

steroid nucleus ring structure. OH groups are below plane of the sterol ring, with methyl groups above. polar and nonpolar face.

Question 16

bile acid synthesis

Answer 16

OH groups added to sterol ring structure, double bond in B ring reduced, hydrocarbon chain is shortened and a carboxyl group added to the end.
rate limiting step is addition of hydroxyl group at carbon 7 of cholesterol. this enzyme gets downregulated by bile acids

Question 17

conjugated bile salts

Answer 17

bile acids are conjugated to serine or taurine before they leave the liver. amide bond between carboxyl of bile acid and amino group of serine/taurine. better detergents due to increased amphipathic nature

Question 18

cholelithiasis

Answer 18

disruption of secretion process by decrease in bile salt production or increased cholesterol secretion causes too much cholesterol. it precipitates and forms gall stones. need laproscopic surgery to fix