Ch. 20 Lipid Metabolism Flashcards
Functions of prostaglandins
Prostaglandins (found in prostate cells) are signaling hormone lipids.
They are made from arachidonate groups (arachadonic acid (C20 fatty acid)) in response to signal.
Prostaglandin Biosynthesis
Biosynthesis Two main steps:
Done by the prostaglandin H2 synthase (COX) enzyme
- Cyclooxygenase activity:
formation of cyclopentane ring by O2 oxidation of arachidonate
- Peroxidase activity:
cleaves the hydroperoxide to an alcohol
What is the step in prostaglandin biosynthesis that is inhibited by certain drugs, including aspirin and NSAIDs?
These drugs are COX inhibitors (aka they inhibit the enzyme)
Aspirin: acetylates a Ser residue on the enzyme
Ibuprofen and Acetaminophen: noncovalently bind to the enzyme and block the active site.
Describe how statins reduce cholesterol levels
Statins bind and inhibit HMG-CoA reductase and can be used to treat high cholesterol levels.
Describe the types of reactions and the sequence of reactions required to produce a molecule of cholesterol from HMG-CoA.
Initial before steps: Convert 3 Acetyl-CoA to HMG-CoA (hydroxymethylglutaryl-CoA) & then HMG-CoA then has to be converted to “Activated” isopentenyl phyphosphate in 4 steps
1. HMG-CoA Reductase:
Location: cytosol of liver cells
It is the Rate determining step of cholesterol biosynthesis
What’s happening: 4 electron reduction of thioester to an alcohol
2. Mevalonate-5-phosphotransferase:
Phosphorylate the alcohol (from the previous step) using ATP
3. Phosphomevalonate kinase
Adds another phosphate using ATP to form pyrophosphate from the phosphate ester
4. Pyrophosphate mevalonate decarboxylase
Decarboxylate-dehydration reaction using ATP to give isopentenyl pyrophosphate
THEN isopentenyl pyrophosphate isomerizes into dimethylallyl pyrophosphate (using isopentenyl pyrophosphate isomerase)
And CONDENSATION of 4 isopentenyl pyrophosphates and 2 dimethylallyl pyrophosphates into cholesterol
