Questions and Answers
What is the product of the pentose phosphate pathway that is used in fatty acid synthesis?
What is the rate-limiting step in fatty acid synthesis?
What is the function of malonyl-CoA in fatty acid synthesis?
What is the byproduct of the condensation reaction between acetyl-CoA and malonyl-CoA?
Signup and view all the answers
What is the enzyme that catalyzes the conversion of oxaloacetate to malate?
Signup and view all the answers
What is the function of the cysteine residue in FAS1?
Signup and view all the answers
What regulates acetyl-CoA carboxylase?
Signup and view all the answers
What is the role of NADPH in fatty acid synthesis?
Signup and view all the answers
What is the product of the reaction catalyzed by the enzyme beta-keto acyl ACP reductase?
Signup and view all the answers
What is the purpose of the pentose phosphate pathway in fatty acid synthesis?
Signup and view all the answers
Study Notes
Fatty Acid Synthesis
Recap of Part One
- Fatty acid synthesis requires glucose, which is converted into pyruvate via the glycolytic pathway
- Pyruvate is taken up into the mitochondria, where it's converted into acetyl-CoA and oxaloacetate
- Acetyl-CoA and oxaloacetate form citrate, which then goes through the Krebs cycle, producing NADH and FADH2
- However, when there's too much ATP, citrate builds up and is transported out of the mitochondria into the cytoplasm
- Citrate lyase converts citrate back into oxaloacetate and acetyl-CoA
Converting Oxaloacetate into Pyruvate
- Oxaloacetate is converted into malate, which is then converted into pyruvate by the malic enzyme
- The malic enzyme generates NADPH, a key precursor for fatty acid synthesis
- NADPH is a strong reducing agent that will be used to reduce molecules in the fatty acid synthesis pathway
Pentose Phosphate Pathway
- An alternative way to generate NADPH is through the pentose phosphate pathway
- Glucose is converted into glucose-6-phosphate, which then enters the pentose phosphate pathway
- The pentose phosphate pathway generates NADPH and ribose-5-phosphate
Acetyl-CoA and Malonyl-CoA
- Acetyl-CoA is a two-carbon structure that needs to be carboxylated to form malonyl-CoA, a three-carbon structure
- The carboxylation reaction is catalyzed by acetyl-CoA carboxylase, a rate-limiting step in fatty acid synthesis
- Malonyl-CoA is a key building block for fatty acid synthesis and is regulated by various molecules and hormones, including insulin, glucagon, norepinephrine, and epinephrine
Regulation of Acetyl-CoA Carboxylase
- Acetyl-CoA carboxylase is regulated by:
- Insulin, which stimulates the enzyme
- Citrate, which allosterically regulates the enzyme
- Glucagon, norepinephrine, and epinephrine, which phosphorylate the enzyme and inhibit it
- Long-chain fatty acids, which inhibit the enzyme
Malonyl-CoA's Role in Regulating Fatty Acid Uptake
- Malonyl-CoA inhibits the activity of carnitine palmitoyl transferase-1 (CPT-1), preventing fatty acids from entering the mitochondria and undergoing beta-oxidation
- This helps to promote fatty acid synthesis over fatty acid breakdown
Fatty Acid Synthase Type 1 (FAS1)
- FAS1 is the enzyme that catalyzes fatty acid synthesis
- FAS1 has two components:
- A cysteine residue with a thio group
- An acyl carrier protein (ACP) with a phosphopantetheine group
- FAS1 will use the three precursors (NADPH, malonyl-CoA, and FAS1 itself) to build fatty acid chains### Fatty Acid Synthesis
- Fatty acid synthesis involves the combination of acetyl-CoA and malonyl-CoA molecules
- Acetyl-CoA is a 2-carbon molecule, while malonyl-CoA is a 3-carbon molecule
- The synthesis process begins with the transfer of an acetyl group from acetyl-CoA to the acyl carrier protein (ACP) end
- This step is catalyzed by the enzyme acetyl transacylase
- The resulting 2-carbon acetyl group is then transferred from the ACP end to the cysteine residue
- This step is catalyzed by the enzyme acyl transacylase
- Next, a malonyl group from malonyl-CoA is added to the ACP end, replacing the CoA group
- This step is catalyzed by the enzyme malonyl transacylase
- The resulting 5-carbon molecule is then condensed with the 2-carbon acetyl group, resulting in a 4-carbon molecule
- This step is catalyzed by the enzyme acyl-malonyl ACP condensing enzyme and involves a decarboxylation reaction, resulting in the loss of one carbon atom
Beta-Keto Reduction and Dehydration
- The resulting 4-carbon molecule is in the form of a beta-keto group
- The beta-keto group is reduced to a hydroxyl group using hydride ions from NADPH
- This step is catalyzed by the enzyme beta-keto acyl ACP reductase
- The resulting hydroxyl group is then dehydrated to form a double bond
- This step is catalyzed by the enzyme 3-hydroxy acyl ACP dehydratase
- The resulting double bond is then reduced to a saturated fatty acid chain using hydride ions from NADPH
- This step is catalyzed by the enzyme enol acyl ACP reductase
Fatty Acid Chain Elongation
- The resulting saturated fatty acid chain is then transferred to the cysteine residue
- The process is repeated, with the addition of a new malonyl group to the ACP end and the condensation of the resulting molecule with the growing fatty acid chain
- This process continues, with the addition of 2-carbon units at a time, until a 16-carbon fatty acid chain is formed
- This process requires 7 rounds of fatty acid synthesis, with the first round forming a 4-carbon chain and subsequent rounds adding 2-carbon units at a time
Fatty Acid Synthesis
Overview
- Fatty acid synthesis requires glucose, converted into pyruvate via glycolysis and then into acetyl-CoA and oxaloacetate in the mitochondria
- Citrate is formed from acetyl-CoA and oxaloacetate, but when ATP is high, citrate is transported out of the mitochondria and converted back into oxaloacetate and acetyl-CoA
Generating NADPH
- Oxaloacetate is converted into malate, then pyruvate, generating NADPH through the malic enzyme
- NADPH is a strong reducing agent used to reduce molecules in fatty acid synthesis
- The pentose phosphate pathway is an alternative way to generate NADPH and ribose-5-phosphate
Acetyl-CoA and Malonyl-CoA
- Acetyl-CoA is carboxylated to form malonyl-CoA, a key building block for fatty acid synthesis, catalyzed by acetyl-CoA carboxylase
- Malonyl-CoA is regulated by insulin, citrate, glucagon, norepinephrine, epinephrine, and long-chain fatty acids
Regulation of Acetyl-CoA Carboxylase
- Insulin stimulates acetyl-CoA carboxylase
- Citrate allosterically regulates acetyl-CoA carboxylase
- Glucagon, norepinephrine, and epinephrine phosphorylate and inhibit acetyl-CoA carboxylase
- Long-chain fatty acids inhibit acetyl-CoA carboxylase
Malonyl-CoA's Role in Regulating Fatty Acid Uptake
- Malonyl-CoA inhibits carnitine palmitoyl transferase-1 (CPT-1), preventing fatty acid uptake for beta-oxidation
- This promotes fatty acid synthesis over breakdown
Fatty Acid Synthase Type 1 (FAS1)
- FAS1 catalyzes fatty acid synthesis with two components:
- Cysteine residue with a thio group
- Acyl carrier protein (ACP) with a phosphopantetheine group
- FAS1 uses NADPH, malonyl-CoA, and FAS1 itself to build fatty acid chains
Fatty Acid Synthesis Process
- Fatty acid synthesis involves combining acetyl-CoA and malonyl-CoA molecules
- Acetyl-CoA is a 2-carbon molecule, while malonyl-CoA is a 3-carbon molecule
- The synthesis process begins with the transfer of an acetyl group from acetyl-CoA to ACP
- The resulting 2-carbon acetyl group is then transferred to the cysteine residue
- A malonyl group from malonyl-CoA is added to ACP, replacing the CoA group
- The resulting 5-carbon molecule is condensed with the 2-carbon acetyl group, resulting in a 4-carbon molecule
- The 4-carbon molecule undergoes beta-keto reduction and dehydration to form a saturated fatty acid chain
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Recap of the first part of fatty acid synthesis, covering the process of converting glucose into pyruvate, acetyl-CoA, and citrate, and its relation to the Krebs cycle. Learn about the role of ATP in this process.