Hardman - Synthesis of Fatty Acids Flashcards
Where do the carbons come from to build fatty acids?
Excess Acetyl-CoA
Where are Fatty Acids synthesized?
Cytoplasm
What carries acetyl-CoA across the innner mitochondrial membrane towards the cytoplasm to begin fatty acid synthesis?
What enzyme frees acetyl-CoA in the cytoplasm?
OAA + Acetyl-CoA = Citrate
- Essentially the first step of the citric acid cycle, Citrate can cross the membrane
ATP-citrate lyase
What happens to the citrate once its “carries” acetyl-CoA to the cytoplasm?
What important by-product is formed?
- Acetyl-CoA is “cut” off by lyase
- Left with OAA
- Conversion to Malate requires NADH
- Conversion to Pyruvate gives off NADPH
- Reenters mitochondria
***NADPH IS GENERATED***
What is the source of the NADPH required for fatty acid synthesis of palmitate?
Two sources:
- 8 NADPH from the Citrate cycle of “shuttling” acetyl-CoA to cytoplasm, and subsequent conversion to pyruvate
6 NADPH come from Pentose Phosphate Pathways
What is the first commited step in fatty acid synthesis?
What does this product inhibit?
Formation of 3-Carbon, Malonyl CoA, catalyzed by acetyl CoA Carboxylase (biotin enzyme)
***RATE LIMITING STEP OF FATTY ACID SYNTHESIS***
Product inhibits CPT-1, the rate limiting enzyme of Fatty Acid Oxidation
How does active acetyl-CoA carboxylase exist?
Active = filaments
Inactive = monomers
What are two product based regulators of Acetyl CoA Carboxylase?
How is the enzyme inactivated?
Citrate = Activate
Palmitoyl CoA = Inhibit
Inactivated by Phosphorylation, AMPK
Activated by Deposhorylation, Protein Phosphatase A2
What hormones affect Acetyl CoA Carboxylase?
Glucagon / Epinephrine = Inhibit
You are low on energy, why would you want to synthesize excess fatty acids?
Insulin = Avtivate
You have extra energy, now it’s time to make some to store for later
Adaptive Control
Fasting then feeding increases Acety CoA Carboxylase activity
Where does fatty acid synthesis occur?
How many catalytic sites does this have?
Fatty Acid Synthase
7 sites
Where are intermediate acyl chains attached during synthesis?
Acyl Carrier Protein
Where are all carbons derived from for fatty acid synthesis?
Acetyl CoA
What are the four steps to each round of fatty acid synthesis, and how many carbons are added each round?
Synthesis:
Condensation
Reduction
Dehydration
Reduction
“Synthesis: CRist DR.”
How do you determine how many rounds are required for a carbon chain of n length?
How many NAPH are used?
How many ATP are used?
How many protons are used?
(n-carbons / 2) - 1
2 NAPH / Round
1 ATP / Round
2 Protons / Round
Where does fatty acid synthase stop?
Carbon 16
Where are accesory enzymes for elongation and desaturation of palmitate located?
What is the 2-carbon donor for elongation of palmitate?
Cytoplasmic Face of E.R.
3-Carbon Malonyl CoA, but first decarboxylation must occur
What E.R. enzyme introduces double bonds?
Mixed Function Oxidases
How far can mammals desaturate fatty acids? (what is the limit)
Delta-9 Carbon in the chain
IN PLANTS: What enzyme is key for production of Omega-6 fatty acids?
IN PLANTS: What enzyme is key for production of Omega-3 fatty acids?
Delta-12 Desaturase
Delta-15 Desaturase
Where are eicosanoids derived from?
20-carbon polyunsaturated fatty acids
Where is the site of aspirin activity?
Inhibits:
Prostaglandin Synthase
Thromboxane Synthase
Enzyme to go from Arachidonate to Leukotriene
Lipoxygenase
Role of prostaglandins
Stimulate Inflammation
Control clotting
How do steroid drugs (Cortisone / Prednisone) work?
Inhibit: Inflammation
Phospholipid to Arachidonate (phospholipase A2)
Inhibit: Allergic Response
Arachidonate to PGG2 (COX)
Where do NSAIDs act?
Inhibit cyclooxgenase activity of COX
Prostaglandin (PGH2) is the source for clotting control, what are the two atagonistic producs that control this?
Prostacyclin (PGI2) - Inhibits clotting, promotes vasodilation
Thromboxane A2 - Promotes clotting
Diphosphatidyl Glycerol is found commonly in which membrane?
Mitochondrial Membrane
What is the primary component of lung surfactant?
Dipalmatoyl-phosphatidylcholine
What is an example of an ether glycerophospholipid?
Platelet Activating Factor
