Metabolism 6: Synthesis of FA and TAGs Flashcards
What favors lipid metabolism, fed or fasting state?
Fed state. Insulin promotes the Acetyl-CoA Carboxylase to convert Acetyl-CoA to Fatty Acyl-CoA which can then be used to generate TAGs
This state also favors using Acetyl-CoA to form cholesterol
What does the fasting state favor?
Epinephrine drives the formation of acetyl-CoA and ketone bodies from fatty acyl-CoAs
How is the transportation of fatty acid diffferet in the fed and fasting states?
Fed State: FA transported as part of TAGs on lipoproteins to be sent with chylomicrons to muscle and adipose tissue
Fasting: FA from adipose tissue transported bound to albumin to be sent to muscle and liver for generateing ketone bodies and energy production via oxidation
What is Palmitic fatty Acid?
16:0
Product of FA synthesis
What is Stearic Fatty Acid ?
Stearic Fatty Acid
18:0
Has common chain length
What is linoleic fatty acid?
Essential fatty acid (Omega 3)
18: 2 (9,12)
18: 3(9,12,15)
What is arachaidonic acid?
Precursor of prostaglandin
20:4(5,8,11,14)
What is the stoichiometric reaction for fatty acid biosynthesis?
Acetyl-CoA + 7 Malonyl CoA + 14 NADPH + 14H+ -> Palmitate + 7 CO2 + 14 NADP + 8 CoA + 6 H2O
What does Acetyl-CoA Carboxylase do?
Forms 7 Malonyl CoA from 7 Acetyl-CoA along with 7 CO2, which later reacts with ACetyl CoA to form Palmitoyl CoA via fatty acid synthesis
What does fatty acid biosynthesis require?
Acetyl Groups: transported from mitochrondria via citrate
Acetyl-CoA CArboxylase: form malonyl CoA
Biotin: carrier of activated CO2
Fatty Acid Synthase Complex: Use 1 Acetyl CoA and 7 Malonyl CoA to synthesize even numbered saturated fatty acids
NADPH
Where do the carbons from fatty acid synthesis come from?
Acetyl CoA (ultimately)
What is the significance of citrate in fatty acid synthesis?
Used to transport acetyl groups from mitochondria to cytosol
Allosterically activates Acetyl-CoA Carboxylase
**Also used to regenerate pyruvate via covnersion to oxaloacetate after losing acetyl-CoA
Explain the citrate shuttle
Mitochondrial Matrix: Oxaloacetate and Acetyl-CoA combine via citrate synthase -> citrate formed
Citrate trasported out of mitochondria to cytosol -> ATP-Citrate lyase -> Oxaloacetate and Acetyl-CoA reformed again
What is the significance of Acetyl-CoA Carboxylase?
Rate limiting enzyme in FA biosynthesis
Catalyze formation of Malonyl CoA from Acetyl CoA
Requires biotin as a cofactor that carries activated oxygen
What regulates Acetyl-CoA Carboxylase?
Allosteric:
+: citrate
-: Palmitoyl CoA (downstream product), AMP
Hormonal
+: insulin (leads to dephosphorylation of enzyme)
-: glucagon, epinephrine (leads to phosphorylation of enzyme)
What is the signfiicance of Malonyl CoA?
It is the product of the rxn catalyzed by Acetyl-CoA Carboxylase.
It inhibits the rate limiting enzyme of fatty acid oxidation (beta ox) and ketone body formation
What are some long term regulating factors of Acetyl CoA Carboxylase?
Increased Enzyme Synthesis: high carb diet, insulin, thyroid hormone
Decreased Enzyme Synthesis: High fat diet, fasting glucagon
What is the Fatty Acid Synthase Complex (FAS)
7 enzyme activity complex that catalyzes the formation of fatty acids from 1 Acetyl-CoA and 7 Malonyl CoA
What is the stoichiometric reaction carried out by FAS complex?
Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14H+ -> Palmitate + 7CO2 + 14 NADP + 8 CoA + 6H2O
What happens in the first cycle of the FAS complex?
Acetyl-CoA combines with a 2 carbon acetyl group from Malonyl CoA to create a 4C butyryl group
What happens in the last 6 cycles of the FAS complex?
a 2C acetyl group from Malonyl CoA is added to the growing fatty acid chain from the 4C Butyryl group formed from the 1st cycle untili a 16C saturated FA Palmitate is formed
What are the 6 enzymatic steps in 1 cycle of the FAS complex?
Acetyl Transferase: transfer Acetyl from Acetyl-CoA to ACP => Acetyl-ACP
Malonyl Transferase: transfer malonyl from Malonyl-CoA to ACP => Malonyl-ACP
Ketoacyl Carrier Protein Synthase: CONDENSATION; Combine Acetyl-ACP and Malonyl-ACP to create acetoacetyl-ACP and CO2
Ketoacyl-ACP Reductase: REDUCTION; Reduce Acetoacetyl-ACP with NADPH to get D3hydroxybutyryl-ACP
3Hydroxyacyl-ACP Dehydratase: DEHYDRATION; Dehydrate to form crotonyl-ACP and lose water
Enoyl-ACP Reductase: REDUCTION reduce crotonyl-ACP with NADPH to get butyryl-ACP our final product
*6 more of these to get palmitic acid
What is an allosteric regulator of the FAS complex?
Fructose 1,6 bisphosphate (Allosteric Activator)
What are long term methods of regulation of the FAS complex?
Increased Enzyme Synthesis: high carb diet via insulin, fat free diet
Decreased Enzyme Synthesis: Glucago, High fat diet via low insulin and high fasting glucagon
What is an example of a polyunsaturated essential fatty acid?
Linoleic Fatty Acid. Must be obtained from diet
What can happen to fatty acids after they are synthesized
Can be elongated
Can be desaturated
Eventually they will be esterified to TAGs, phospholipids, cholesterol
What is the primary regulator for the endogenous synthesis of TAGs?
Substrate availablity
What are PPARs?
Peroxisome Proliferator-Activated Receptors that promote TAG deposition
What happens to TAGs that are syntehsized in the liver?
Packaged into VLDL and sent out into lymph and then TAG is released into capillaries
What happens to dietary triacylglycerols?
In the intestines, they are emulsified by bile acids and digested with lipase to generate fatty acid and a monoacylglycerol molecule. The monoacylglycerol is then packaged along with synthesized TAGs into lipoproteins and then into chylomicrons for transport into circulation
