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?)
What do statins do?
They prevent cholesterol synthesis by COMPETITIVELY inhibiting HMG-CoA reductase. It’s a billion dollar industry.
How does glucagon regulate HMG-CoA reductase?
It phosphorylates the enzyme, which deactivates it
How does insulin regulate HMG-CoA reductase?
It dephosphorylates the enzyme, which activates it
How do ATP and AMP concentrations regulate cholesterol synthesis?
High ATP/low AMP -> increased cholesterol synthesis
Low ATP/high AMP -> decreased cholesterol synthesis
How does diabetes mellitus affect people?
Cannot use glucose for glycolysis AND CANNOT make fatty acids from carbs or amino acids
Describe the big-picture version of glyceroneogenesis
It’s the abbreviated version of gluconeogenesis, from pyruvate to DHAP - > glyceraldehyde 3-P -> TAGs
