Biosynthesis of Cholesterol

Where does biosythesis of cholesterol happen?

in the cytosol

How many carbons are there and where are they from?

There are 27Cs and theya re from Acetyl-CoA

What does cholesterol contain?

isoprene with five carbons

What are the four stages of cholesterol synthesis?

1. 3 acetyl-coa to mevalonate

2. generation of isoprene

3. condensation of isoprene to squalene

4. conversion of squalene to 4 fused ring steroid

what are the first three steps of stage one?

first two exactly like ketone body formmation

1. thiolose

2. HMG-CoA sythase

3. HMG-CoA reductase

what is first step of stage 1 of chol. synth.

Thiolase

Transferase that condenses two acetyl-CoA molecules to form acetoacetyl-CoA

What is 2nd step of stage1 of chol. synth.

HMG-CoA synthase

Catalyzes addition of another acetyl-CoA to from HMG-CoA

Why is cytosolic synthase distict from mito chondrial one

What is step three of stage 1 of chol. synth.

HMG-CoA reductase

• reduces HMG-CoA to mevalonate

• NADPH is oxidized to NADP+ Regenerate NADPH via PPP -RDS

How is HMG-CoA reductase regulated

1. phosphorylation, inactivates HMG-CoA reductase

2. amount of enzyme present in cell, negative inhibition of itself

• cholesterol postivily feed back,

• high intracellular chol. triggers attachment of ubiquitin molecules to hmg-coa reductise, which targets them for degradation

What is hypercholesterolemia

When there is high circulating cholesterol, statins are often prescribed

• inhibit hmg-coa reductase

• contain hmg-coa -like structures so they bind their active site, acting as comp inhibs,

What is stage 2

Requires 3 atp molecules, 2 phosphates get added to mevalonate, one atp is used for LG to generate isoprene

Stage 3

Condense 6 isoprene units to make squalene

Stage 4

Conversion of squalene to 4-fused ring steroid