Fatty acid synthesis Flashcards
What are the primary functions of fatty acids?
Energy storage (triacylglycerols).
Membrane structure (phospholipids).
Signaling (e.g., prostaglandins from arachidonic acid).
Protein modification (myristoylation, palmitoylation).
Where does fatty acid synthesis occur in the cell?
In the cytosol, using acetyl-CoA transported from mitochondria as citrate.
How does acetyl-CoA exit the mitochondria for fatty acid synthesis?
Acetyl-CoA combines with oxaloacetate to form citrate, which is transported to the cytosol. Citrate is then cleaved back into acetyl-CoA and oxaloacetate.
What are the three main stages of fatty acid synthesis?
Production of acetyl-ACP and malonyl-ACP.
Initiation: Condensation of acetyl and malonyl groups to form a 4-carbon chain.
Elongation: Repeated addition of 2-carbon units from malonyl-ACP.
What is the role of ACP (Acyl Carrier Protein)?
ACP carries the growing fatty acid chain between active sites of enzymes during elongation.
When and where does fatty acid synthesis primarily occur?
Fatty acid synthesis primarily occurs in the liver during a fed state when blood glucose levels are high. It can also happen in other tissues and when cellular ATP levels are high. It’s stimulated by insulin.
What are the initial steps of glucose conversion leading to citrate formation in fatty acid synthesis?
Glucose is converted to pyruvate, which enters the mitochondria and is converted to acetyl-CoA. Acetyl-CoA then combines with oxaloacetate to form citrate.
What is the role of citrate in fatty acid synthesis when ATP levels are high?
When ATP levels are high, citrate is not converted to alpha-ketoglutarate within the mitochondria. Instead, it passes through the mitochondrial membrane into the cytoplasm.
What is the function of citrate lyase?
Citrate lyase is an enzyme in the cytoplasm that breaks down citrate back into oxaloacetate and acetyl-CoA, adding a coenzyme A to form acetyl coenzyme A.
Which enzyme catalyzes the rate-limiting step of fatty acid synthesis?
Acetyl-CoA carboxylase (ACC), which converts acetyl-CoA to malonyl-CoA.
What cofactor does ACC require, and what is its role?
Biotin carries activated CO₂ for carboxylation of acetyl-CoA to malonyl-CoA.
Describe the elongation phase of fatty acid synthesis.
Condensation: Malonyl-ACP adds 2 carbons.
Reduction: NADPH reduces keto group to alcohol.
Dehydration: Removes water to form double bond.
Reduction: NADPH reduces double bond to single bond.
How are fatty acids released from the synthase complex?
Thioesterase cleaves the fatty acid from ACP, producing palmitate (16:0) or stearate (18:0).
What is the role of NADPH in fatty acid synthesis?
Provides reducing power for reduction steps (e.g., converting keto groups to CH₂).
Explain the role and importance of Acetyl-CoA Carboxylase (ACC) in fatty acid synthesis.
ACC is a crucial enzyme that converts acetyl-CoA into malonyl-CoA by adding a carbon, using biotin as a coenzyme. Malonyl-CoA is a three-carbon molecule and a key precursor for fatty acids.
How is Acetyl-CoA Carboxylase (ACC) regulated?
ACC is regulated allosterically (stimulated by citrate, inhibited by long-chain fatty acids) and hormonally (stimulated by insulin, opposed by cortisol, glucagon, epinephrine, and norepinephrine).
Describe the active and inactive forms of ACC and what influences them.
ACC exists in an inactive dimer form and an active polymerized form. Citrate and insulin promote the active, polymerized form, while long-chain fatty acids promote the inactive, dimeric form.
Why is NADPH important for fatty acid synthesis, and where does it come from?
NADPH is a crucial reducing agent needed for fatty acid synthesis. It is generated from the malic enzyme (which converts malate to pyruvate) and the pentose phosphate pathway.
How do insulin and glucagon/epinephrine hormonally regulate ACC activity?
Insulin activates phospho-protein phosphatases, which dephosphorylate and activate ACC. Glucagon and epinephrine activate protein kinase A, which phosphorylates and inactivates ACC.
What is malonyl-CoA’s role in the overall process?
Malonyl-CoA, formed by ACC, is the direct precursor molecule used to build up fatty acid chains.
What is the role of AMPK in fatty acid synthesis?
AMPK acts as a cellular “fuel gauge.”
High AMP (low energy) → AMPK phosphorylates ACC → inhibits synthesis.
High ATP → AMPK inactive → synthesis proceeds.
How does citrate regulate ACC?
Citrate (high energy signal) promotes ACC polymerization into active filaments.
What feedback mechanism inhibits fatty acid synthesis?
Palmitoyl-CoA (end product) inhibits ACC and citrate transport out of mitochondria.
What are the three main components needed for fatty acid synthesis
NADPH (for reducing power), Malonyl-CoA (as the building block), and Fatty Acid Synthase Type 1 (FAS I) (the enzyme that catalyzes the process).
