Lecture 13 Flashcards
What are the domains in fatty acid synthase?
Malonyl/acetyl-CoA/ACP transacylase (MAT)
KS (ketone synthase), KR (ketoreductase), DH (dehydratase), ER (enoyl-reductase), and TE (thioesterase)
What is step 1 in the fatty acid synthase process of fatty acid biosynthesis (assume malonyl-CoA was already made)?
MAT adds starting acetyl-CoA to malonyl-CoA, the latter of which is attached to fatty acid synthase by its thiol group
With which step is the first step of fatty acid synthase parallel to in beta-oxidation?
Products of thiolytic cleavage
What is step 2 in the fatty acid synthase process?
Ketone synthase (KS) carries out the condensation reaction. Releases CO2 so that acetyl-CoA can attach
What is step 3 in the fatty acid synthase process?
Ketone reductase (KR) reduces the beta-carbon ketone to an alcohol, using NADPH as an electron donor
What is step 4 in the fatty acid synthase process?
Dehydratase converts beta-carbon hydroxyl to carbon-carbon double bond
What is step 5 in fatty acid synthase?
Enoyl-reductase (ER) reduces the carbon-carbon double bond to hydrocarbons. NADPH used as electron donor.
What is step 6 in fatty acid synthase?
Repeat steps 2-5 as needed
What is step 7 in fatty acid synthase?
Thioesterase (TE) releases the final product, a fatty acid
How many ATP and NADPH does one round of fatty acid biosynthesis consume?
1 ATP and 2 NADPH
Differences between beta-oxidation and fatty acid biosynthesis?
beta-oxidation: CoA is the acyl carrier, FAD and NAD+ are the electron acceptors, L-beta-hydroxyacyl group in dehydration step, C2 unit product is acetyl-CoA
FA biosynthesis: ACP is the acyl carrier, NADPH is the electron donor, D-beta-hydroxyl group in hydration step, C2 unit donor is malonyl-CoA
How does eating Omega-3/6 fatty acids affect inflammatory responses?
They reduce inflammation responses. Paradoxically, they also increase inflammatory response?
What do NSAIDs do?
They inhibit the conversion of arachidonic acid (Omega-6 FA) and eicosapentaenoic acid (Omega-3 FA) to downstream products that increase inflammation response.
What does phospholipase do in inflammatory response?
It releases a free FA to make prostaglandins
What are 2 essential FAs? Do we synthesize them?
Linoleate and alpha-linolenate. We do not synthesize them, rather we eat them from fish, who eat the plants that have the FAs.
What are the 2 precursors for making glycerophospholipids?
Fatty acyl-CoA and L-glycerol 3-P
How to make L-glycerol 3-P?
Glyceroneogenesis, where glycerol kinase converts glycerol to L-glycerol 3-P (Requires ATP input. Release ADP). Can also get it from glycolysis and gluconeogenesis.
Describe phospholipid synthesis. Alternative path?
Acyl-CoA synthetase converts fatty acid to fatty acyl-CoA, which reacts with L-glycerol 3-P to form an acid. A head group is attached to make a glycerophospholipid. An alternative path is to make DAG and then TAG from the acid.
Do we have a mechanism to degrade cholesterol?
No. It must either be used or excreted through the liver.
When do we make cholesterol?
After we eat. Maybe to make bile salts?
Describe big-picture cholesterol synthesis
- Acetate
- Mevalonate (commited to making isoprene)
- Isoprene
- Squalene
- Cholesterol
Describe mevalonate synthesis
- 2 Acetyl-CoA react via thiolase to make acetoacetyl-CoA
- Another acetyl-CoA is added to make HMG-CoA via HMG-CoA synthase
- HMG-CoA reductase uses 2 NADPH to reduce HMG-CoA to mevalonate
Where does mevalonate synthesis occur?
Cytosol, so it doesn’t compete with ketogenesis in the mitochondria
Which hormones regulate HMG-CoA reductase?
Glucagon inhibits it bc don’t want to make fatty acids when hungry
Insulin activates it bc want to make fatty acids (for bile salts?)
