MMT: fatty acid biosynthesis Flashcards
What is the main product of fatty acid synthase?
Palmitic acid
What are the transporters of fatty acids in the fed state?
Chylomicrons and VLDL
What are the transporters of fatty acids in the fasting state?
Albumin
In the fed state, fatty acids are released by?
LPL in the capillaries
In the fasting state, fatty acids are released by?
Hormone-sensitive lipase in adipocytes
What are the 4 major stages of palmitate formation?
- Pyruvate formation 2. Citrate formation 3. Malonyl CoA formation 4. Palmitate
What is the rate limiting enzyme of fatty acid synthesis?
Acetyl CoA carboxylase
In the fed state, what drives the formation of citrate?
Acetyl CoA buildup
How does the high insulin/glucagon ratio in the fed state drive formation of citrate?
It reduces the need for gluconeogenesis and upregulates glycolysis, allowing oxaloacetate that is formed to be used to make citrate
How does a high ATP/ADP ratio in the fed state impact the formation of citrate?
It reduces the need for acetyl CoA to be used in the citric acid cycle, making it available to make citrate
What enzyme is upregulated in the fasting state to promote formation of oxaloacetate?
Pyruvate carboxylase
What vitamin is needed to produce malonyl CoA from acetyl CoA?
Biotin (acetyl CoA carboxylase)
Malonyl CoA inhibits…? What is the significance of this?
CPTI; upregulates fatty acid synthesis instead of oxidation
What is the ‘short arm’ of fatty acid synthase?
Cysteine; associated with acetyl group
What is the ‘long arm’ of fatty acid synthase?
ACP; associated with malonyl group
What is the structure of fatty acid synthase?
A dimer that makes 2 palmitic acids at a time
What is the 4-reaction cycle of fatty acid synthesis?
- Condensation 2. Reduction 3. Dehydration 4. Reduction
What is used as a reducing agent in fatty acid synthesis?
NADPH
Where does fatty acid synthesis occur?
The cytoplasm
What happens once palmitate is formed?
It is released from fatty acid synthase and converted to palmitoyl CoA
What enzyme forms palmitoyl CoA?
Fatty acyl CoA synthase
What is the major control point of fatty acid synthesis?
Acetyl CoA carboxylase
What are the main regulatory methods of acetyl CoA carboxylase?
Phosphorylation and allosteric modulators
More citrate will __ fatty acid synthesis?
Promote
More palmitoyl CoA will __ fatty acid synthesis?
Reduce
Describe the regulation of ACC in the fed state.
Insulin promotes a phosphatase that promotes formation of malonyl CoA and thus inhibition of CPTI. This leads to synthesis of fatty acids.
Describe the regulation of ACC in the fasting state.
High AMP causes AMPK to phosphorylate ACC, causing less malonyl CoA. This will promote fatty acid oxidation as opposed to synthesis.
What enzymes upregulate fatty acid synthesis due to insulin?
Malic enzyme and citrate lyase
Elongation of fatty acids occurs in the…
ER
Where does VLC FA oxidation take place?
Peroxisomes
What are the steps for elongation of fatty acids?
Same as synthesis! 1. Condensation 2. Reduction 3. Dehydration 4. Reduction
In unsaturated fatty acids, where can we introduce double bonds?
Carbon 4, 5, 6, and 9, but not beyond 9!!
What is fatty acyl CoA desaturase?
A membrane-bound oxygenase that desaturates fatty acids in the ER
What does desaturation require to occur?
Iron
What are the main functional roles of fatty acids?
- Serve as fuel 2. Make up TGs and phosphoacylglycerols 3. Serve as hormones and intracellular messengers
Why does the brain not use free fatty acids for fuel?
- ATP generation from beta oxidation demands more oxygen than from glucose, which increases risk of neural hypoxia 2. Superoxide is generated in beta oxidation which can cause oxidative stress 3. Rate of ATP generation is slower than that of glucose
What is the starting molecule for phosphoacylglycerol?
G3P
Other than cell membranes, where can phosphoacylglycerols be found?
Outside of lipoproteins
What are eicosanoids?
Molecules formed from arachidonic acid that act as local hormones; they can cause inflammation, clotting, smooth muscle contraction, etc
Where is arachidonic acid in the cell membrane?
In the fatty acid tails of phospholipids
What are the pathways of eicosanoid synthesis?
COX and LOX
Aspirin and ibuprofen block…
COX
