Fatty Acid and Triacylglycerol Metabolism Flashcards
What are the two main sites of fatty acid de novo synthesis?
1) Liver after a carbohydrate rich meal
2) Lactating mammary gland
What can be achieved by fatty acid de novo synthesis in the liver after a carbohydrate rich meal?
Fatty acid de novo synthesis in the liver reduces the high blood glucose level
after a carbohydrate-rich mean and it also provides fatty acids for eventual
storage in TAGs in fat cells.
Which metabolic condition leads to high citrate levels in liver mitochondria?
A high carbohydrate diet leads to increased citrate in liver mitochondria
What happens to the citrate in liver mitochondria after a carb rich meal
High citrate levels in liver mitochondria lead to transfer of citrate into the cytosol
Describe the cellular location of citrate lyase and describe the irreversible reaction catalyzed by this enzyme.
-Citrate lyase is found in cytosol.
-Citrate and CoA and ATP are the substrates and products are acetyl CoA ,
oxaloacetate , ADP and Pi
Describe the cellular location and the reaction catalyzed by the malic enzyme.
- The malic enzyme is found in liver cytosol.
- Malate and NADP+ are substrates and products are pyruvate, CO2 and NADPH
What is the dietary precursor to arachidonic acid?
Linoleic acid
Biosynthesis of fatty acids most likely occurs in which state?
Well-fed state
Where does Acetyl CoA produced in mitochondria come from?
- oxidation of pyruvate (PDH complex)
- Degradation of fatty acids
- Degradation of ketone bodies
- Degradation of amino acids
What happens when ATP is high in the mitochondria which causes Acetyl CoA to be converted to citrate?
Isocitrate dehydrogenase is inhibited
What is Acetyl CoA converted to for transport in the cytosol?
Citrate
Once in the cytosol, what enzyme converts Citrate into Acetyl CoA and Oxaloacetate?
ATP-Citrate lyase
Which enzyme produces NADPH in order to be used in Fatty Acid synthesis?
Malic enzyme
converts malate to pyruvate
Which enzyme catalyzes the first committed step of fatty acid biosynthesis?
Acetyl CoA Carboxylase (ACC)
What is the rate-limiting enzyme for fatty acid synthesis?
Acetyl-CoA Carboxylase
Which cofactor does Acetyl CoA Carboxylase need?
Biotin
Acetyl CoA Carboxylase requires how many ATP molecules per malonyl-coA formed?
1 ATP
The enzyme Acetyl CoA Carboxylase converts _____ to _____
Acetyl CoA
Malonyl CoA
What two molecules are used in short term allosteric regulation of Acetyl CoA Carboxylase?
Citrate
Palmitoyl CoA
How does citrate allosterically regulate Acetyl CoA Carboxylase?
Citrate shifts the polymer - monomer equilibrium towards polymer formation –> activation
How does Palmitoyl CoA allosterically regulate Acetyl CoA Carboxylase?
Palmitoyl CoA shifts the equilibrium toward monomer formation –> inhibition
What contributes to short term HORMONAL regulation of Acetyl CoA Carboxylase?
Glucagon
Epinephrine
Norepinephrine
How do glucagon, epinephrine and norepinephrine act upon Acetyl CoA Carboxylase?
Trigger cAMP dependent phosphorylation of enzyme (through activation of AMPK) that shifts the equilibrium toward monomer formation (inactive form).
How does high carb, fat free diet lead to Long term regulation of Acetyl CoA Carboxylase.
Up-regulation/ induction of ACC resulting in increased synthesis of FA
How do high-fat diets, fasting ad glucagon levels regulate Acetyl CoA Carboxylase long term?
Lead to decreased synthesis (down regulation, repression) resulting in decreased synthesis of FA
Which form of Fatty Acid Synthase is the fully functional form?
Dimeric
How does insulin effect Fatty Acid Synthase?
Upregulates the amount of enzyme expressed
In the first reaction of FA synthesis, Acetyl CoA is added to a ______ group of which domain of FAS?
Cysteine-SH group; Condensing Enzyme (CE) domain
What is added in the second reaction of FA synthesis?
Malonyl CoA
Which group is Malonyl CoA added to in the second step of FA synthesis?
ACP sulfhydryl group
ACP= acyl carrier peptide
What occurs during the 3rd reaction of FA synthesis?
Acetyl group is transferred to the Malonyl Group with the release of carbon dioxide
Regarding the 4th step of FA synthesis, the _______ is _______ to a ______ by the ________ activity.
Keto group;
Reduced;
Hydroxyl group;
Beta-ketoacyl reductase
Regarding the 5th reaction, what is dehydrated to form a trans-monounsaturated fatty acyl group?
Beta-hydroxybutyryl-ACP
What occurs in the 6th reaction of Fatty Acid synthesis
An acyl group is converted to a butyryl group
Then, butyryl group is transferred from ACP sulfhydryl group to CE sulfhydryl
What occurs after step 6 in FA synthesis?
The butyryl group is now ready to condense with a new malonyl group (step 3) to repeat the process
Regarding FA Synthesis, Once the fatty acyl group reaches its final carbon chain length, what occurs in step 7?
Thioesterase activity hydrolyses it, forming final free form.
What modifications are typically made to produce variety in fatty acids?
- chain elongation to give longer fatty acids
- desaturation, giving unsaturated fatty acids
Where does chain elongation of fatty acids primarily occur?
Membranes of ER and involves addition of malonyl CoA to palmitate.
Where is the minor elongation pathway of fatty acids and how does it occur?
Mitochondria;
Reversal of B-oxidation.
What introduces sites of unsaturation (double bonds) in fatty acids?
Fatty acyl-CoA desaturases
In the fatty acid desaturation system, what positions are doubles bonds introduced by fatty acyl-CoA desaturases?
5, 6 or 9
Why are linoleate and linolenate considered essential fatty acids?
Because they have unsaturations beyond carbon 9
What 3 enzymes are involved in the fatty acid desaturase system (an electron transport system in the ER)
1) cytochrome b5
2) desaturase
3) NADPH-cytochrome b5 reductase
What are the substrates in phosphatic acid synthesis?
DHAP–> Glycerol-3-Phosphate –> Monoacylglycerol-3-phosphate—> Phosphatic Acid
DHAP is converted to Glycerol-3-phosphate using which enzyme?
Glycerol-3-phosphate
What are the substrates of TAG synthesis?
Phosphatic acid –> 1,2-Diacylglycerol–> TAG
