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Questions and Answers
What is the main difference between chain elongation in microsomes and chain elongation in mitochondria?
What is the main difference between chain elongation in microsomes and chain elongation in mitochondria?
Which enzyme replaces thiolase in the chain elongation process in mitochondria?
Which enzyme replaces thiolase in the chain elongation process in mitochondria?
What is the function of the chain elongation system in mitochondria under anaerobic conditions?
What is the function of the chain elongation system in mitochondria under anaerobic conditions?
Which of the following is a dietary essential fatty acid that mammalian cells cannot produce?
Which of the following is a dietary essential fatty acid that mammalian cells cannot produce?
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How is glycerol activated for incorporation into triacylglycerols in muscle or adipose tissue?
How is glycerol activated for incorporation into triacylglycerols in muscle or adipose tissue?
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What is the first step in the synthesis of triacylglycerols (TAGs)?
What is the first step in the synthesis of triacylglycerols (TAGs)?
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Where does de novo synthesis of fatty acids primarily occur in mammals?
Where does de novo synthesis of fatty acids primarily occur in mammals?
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What is the main starting material used for fatty acid synthesis?
What is the main starting material used for fatty acid synthesis?
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Which of the following is NOT a system involved in fatty acid synthesis?
Which of the following is NOT a system involved in fatty acid synthesis?
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Which molecule is utilized in the synthesis of fatty acids as part of the process?
Which molecule is utilized in the synthesis of fatty acids as part of the process?
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What are the three main metabolic pathways that produce acetyl CoA?
What are the three main metabolic pathways that produce acetyl CoA?
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How is acetyl CoA transported from the mitochondria to the cytosol?
How is acetyl CoA transported from the mitochondria to the cytosol?
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What happens to citrate once it is in the cytosol?
What happens to citrate once it is in the cytosol?
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Which metabolic process primarily contributes to the formation of acetyl CoA from fatty acids?
Which metabolic process primarily contributes to the formation of acetyl CoA from fatty acids?
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What enzymatic reaction occurs when malate is catalyzed by malic enzyme?
What enzymatic reaction occurs when malate is catalyzed by malic enzyme?
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Which enzyme is responsible for the committed step in fatty acid synthesis?
Which enzyme is responsible for the committed step in fatty acid synthesis?
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What is the net result of amino acid degradation regarding acetyl CoA?
What is the net result of amino acid degradation regarding acetyl CoA?
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What is the primary reducing agent used during the chain elongation of fatty acids in microsomes?
What is the primary reducing agent used during the chain elongation of fatty acids in microsomes?
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What happens to oxaloacetate after being formed from citrate in the cytosol?
What happens to oxaloacetate after being formed from citrate in the cytosol?
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What role does excess glucose play in fat deposition?
What role does excess glucose play in fat deposition?
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Which of the following steps in the extramitochondrial pathway is the rate-limiting step?
Which of the following steps in the extramitochondrial pathway is the rate-limiting step?
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What effect does glucagon have on fatty acid synthesis?
What effect does glucagon have on fatty acid synthesis?
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Which component of fatty acid synthase carries the acyl groups during fatty acid synthesis?
Which component of fatty acid synthase carries the acyl groups during fatty acid synthesis?
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Acetyl CoA carboxylase is activated by which of these conditions?
Acetyl CoA carboxylase is activated by which of these conditions?
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In which cellular structures does fatty acid elongation primarily occur in mammals?
In which cellular structures does fatty acid elongation primarily occur in mammals?
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Which of the following statements about fatty acid synthesis is false?
Which of the following statements about fatty acid synthesis is false?
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Study Notes
Fatty Acid Synthesis Overview
- Fatty acid synthesis, also known as lipogenesis, primarily creates triacylglycerols (TAGs) from carbohydrates.
- Starting materials include fatty acids (acyl CoA) and glycerol (glycerol-3-P).
- The process involves multiple steps.
Fatty Acid Synthesis Steps
- Biosynthesis of fatty acid: This is a critical initial step.
- Activation of fatty acid: This prepares fatty acids for incorporation.
- Biosynthesis of glycerol-3-P: Another necessary step for TAG formation.
- Combination of steps 2 and 3: This combines activated fatty acids and glycerol-3-P to form TAGs.
Biosynthesis of Fatty Acids: Systems
- There are three main systems for fatty acid synthesis:
- De novo synthesis in the cytoplasm
- Chain elongation in mitochondria
- Chain elongation in microsomes
De Novo Synthesis of Fatty Acids (FA)
- This process is the opposite of beta-oxidation.
- It occurs in the cytoplasm.
- It uses 2-carbon acetate units to build even-chain, saturated fatty acids.
- It differs from fatty acid degradation, utilizing acyl carrier protein (ACP) instead of CoA.
- It employs enzymes linked in a complex.
- It uses NADPH as its reducing power.
- Unique pathways (unlike glycolysis/gluconeogenesis) occur.
- In mammals, this process mainly takes place in the cytosol of liver and adipose tissue, and mammary glands during lactation.
- Acetyl-CoA is the primary starting material for FA synthesis, though most acetyl-CoA comes from carbohydrate metabolism in mitochondria.
Acetyl-CoA Sources
- Acetyl-CoA comes from various sources:
- Carbohydrates (glycogen, glucose)
- Fats (fatty acid oxidation)
- Proteins (amino acid deamination)
1-Acetyl-CoA from Carbohydrates
- Excess carbohydrates are transported to the cytosol as citrate.
- The citrate is then converted to acetyl-CoA within the cytosol.
- This is a critical process to provide acetyl-CoA from the mitochondria to the cytosol for fatty acid synthesis.
2-Acetyl-CoA from Proteins
- Amino acid degradation leads to acetyl-CoA or citrate.
- Citrate is exported to the cytosol.
- Resulting in acetyl-CoA in the cytosol.
3-Acetyl-CoA from Lipids
- The end product of fatty acid oxidation is acetyl-CoA.
Acetyl-CoA Transport
- Acetyl-CoA cannot pass directly from the mitochondria to the cytosol.
- Instead, acetyl-CoA is converted to citrate, then transported to the cytosol.
- In the cytosol, citrate is converted back to acetyl-CoA and oxaloacetate.
Sources of NADPH
- These molecules are crucial for fatty acid synthesis. Sources include:
- Pentose shunt (HMP) pathway
- Malic enzyme
- UDP-glucose dehydrogenase
- Cytoplasmic isocitrate dehydrogenase
- NAD/NADP transhydrogenase
- Glutamate dehydrogenase
Enzymes for Fatty Acid Synthesis
- Acetyl-CoA carboxylase: Catalyzes the committed, rate-limiting, step in fatty acid synthesis.
- Fatty acid synthase: Multi-enzyme complex consisting of 7 enzymes linked together in a polypeptide chain. Contains acyl carrier protein (ACP), which uses pantothenic acid (vitamin B5) to carry acyl groups during synthesis.
Steps of Extramitochondrial Pathway (De Novo Synthesis)
- Condensation
- Reduction
- Dehydration
- Additional reduction
- Formation of Malonyl CoA is the rate-limiting step.
Regulation of FA Synthesis
-
Allosteric regulation:
- Regulated by citrate (activator)
- Inhibited by long-chain acyl-CoA (product)
- Key enzyme: Acetyl-CoA carboxylase, the rate-limiting step.
-
Hormonal regulation (covalent modification):
- Activated by dephosphorylation (insulin)
- Inactivated by phosphorylation (glucagon)
Fate of Palmitate
- Estrification: Incorporation into triacylglycerols (TAGs)
- Elongation: Extending the fatty acid chain
- Desaturation: Introducing double bonds
Chain Elongation in Microsomes
- The reactions mirror cytosolic fatty acid synthase.
- The primary source for 2-carbon units is malonyl-CoA.
- NADPH is used as the reducing agent.
- Site for lengthening pre-existing fatty acid chains (particularly useful for sphingolipid synthesis).
- Active during nerve myelination.
Chain Elongation in Mitochondria
- Acetyl-CoA is the new 2-carbon precursor.
- NADH and NADPH play roles as reducing agents.
- This pathway operates almost as a reverse form of fatty acid oxidation.
- It's important in situations with high NADH/NAD+ ratios (like in anaerobic conditions).
Biosynthesis of Unsaturated Fatty Acids
- Desaturases introduce double bonds in fatty acid chains.
- Mammals lack the ability to insert double bonds in specific locations.
- Certain polyunsaturated fatty acids (PUFAs) are essential components of the diet.
Biosynthesis of Triacylglycerols (TAGs)
- Glycerol and fatty acids must be activated by ATP before incorporation.
- Occurs primarily in microsomes of tissues like liver, kidney, intestine, and lactating mammary glands.
- Glycerol activation involves a specific enzyme (glycerol kinase).
- Fatty acid activation uses acyl CoA synthetase enzymes.
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Description
Explore the intricate process of fatty acid synthesis, also known as lipogenesis, which transforms carbohydrates into triacylglycerols. This quiz covers key steps like biosynthesis, fatty acid activation, and the systems involved in this essential biochemical pathway.
