Lipid Synthesis Flashcards
(41 cards)
What are the functions of peroxisomes and what do they not produce?
Peroxisomes breakdown very long chain fatty acids through Beta oxidation until the chain length is 20 carbons
Also use alpha oxidation to degrade branched chain fatty acids (phytanic acid)
Synthesize fatty alcohols like plasmoglogens that are enriched in nervous, immune, and cardiovascular system
Peroxisomes do not produce ATP
What is different between perosiomal enzymes and mitochondrial equivalents?
Beta oxidation starts with an oxidase and produces hydrogen peroxide from FADH
What does it mean that peroxisomes do not produce ATP?
No citric acid cycle to oxidize acetyl-CoA
No electron transport chain to oxidize NADH
What is the main oxidase involved in Beta oxidation?
Acyl-CoA Oxidase
How do peroxisomes degrade phytanic acid?
Alpha Oxidation - Cells hvae no other mechanism to degrade branched fatty acids
Process that removes a one carbon fragment from the fatty acid and produces formyl-CoA instead of acetyl-CoA
What often causes peroxisome biogenesis disorders?
Mutations in PEX genes
How does a patient with Zellweger Syndrome present?
Mutation in PEX1 and is a peroxisome biogenesis disorder.
Patient presents with multiple developmental abnormalities, no peroxisomes in liver. Diagnosis includes accumulation of very long chain fatty acids in blood
How does a patient with Refsum disease present?
Alpha oxidation deficiency and is a peroxisomes biogenesis disorder.
Patient presents with multiple developmental abnormalities. Diagnosis includes accumulation of phytanic acid in blood.
What state does fatty acid synthesis occur in and where is synthesis most active?
Fatty acids are synthesized in the fed state.
Most active in the liver and adipose tissue
Where do fatty acid synthesis reactions occur?
In the cytoplasm
What is the significance of mitochondrial acetyl-CoA for fatty acid synthesis?
Fatty acid synthesis starts with acetyl-CoA
Synthesis of fatty acids repress ____
Fatty acid degradation
What are fatty acids converted to in the liver and adipose tissue?
Liver - Triacylglycerol (TAG)
Adipose - TAG droplet
Does the liver store fat?
No! But it makes a lot of it
If fat is found in the liver, it is pathological
What happens to fat made in the liver?
Fat is packed into lipoproteins and moved into circulation.
What happens to fat made in adipose tissue?
Stored!
Brown fat (thermogenic) and white fat (stores)
Adipose tissue is considered an endocrine organ
How does the body get ready to make fatty acids? (general)
Insulin stimulate glucose catabolism, which causes the mitochondria to fill with acetyl-CoA
The acetyl-CoA is exported from the mitochondria to the cytoplasm
Insulin activates the committed step of FA synthesis –> Acetyl-CoA carboxylase
What are the 3 phases of fatty acid synthesis?
- Export of mitochondrial acetyl-CoA into the cytoplasm
- Committing acetyl-CoA to FA synthesis by carboxylation to malonyl-CoA
- Assembling a FA from acetyl-CoA and malonyl-CoA units
How is acetyl-CoA exported from the mitochondria? First phase of FA synthesis
Tricarboxylic Acid Transporter
- Citrate formed from oxaloacetate and acetyl-CoA
- Citrate crosses the inner mitochondrial membrane into the cytosol through the TCA transporter
- ATP-citrate lyase cleaves citrate into its components; acetyl-CoA and oxaloacetate
- Acetyl-CoA used for FA synthesis
- Oxaloacetate is converted into pyruvate via malate dehydrogenase and malic enzyme which yields one molecule of NADPH
Explain the second phase of FA synthesis which is committing acetyl-CoA to FA synthesis
Acetyl-CoA carboxylase converts acetyl-CoA to malonyl CoA (biotin dependent). This enzyme is active in the fed state.
Insulin activates Acetyl-CoA carboxylase through dephosphorylation
What activates and inactivates acetyl-CoA carboxylase?
Activated by dephosphorylation by insulin in fed state
Inactivated during fasting by glucagon. Inactivated by epinephrine and inactive when energy is low (AMP)
Explain the third phase of fatty acid synthesis where FA are synthesized from acetyl-CoA and malonyl-CoA
Fatty Acid Synthases assembles a 16 carbon fatty acid from acetyl-CoA and malonyl-CoA
Steps:
- Acetyl group transferred from acetyl-CoA to acyl-carrier protein site A on FA synthase
- Acetyl group moved from A site to a cysteine residue on C site
- Malonyl-group transferred from malonyl CoA to A site of FA synthase
- Acetyl group on C site moved to alpha carbon of malonyl group on A site and CO2 is released
- Keto group of Beta carbon is removed by 2 reductions and a dehydration reaction –> resulting saturated fatty acid moved back to C site
- Reactions 2-5 are repeated six times until FA on C site is 16 carbons long
- Palmitic acid released from enzyme
Where does the NADPH for the reductions occurring in FA synthase come from?
Pentose Phosphate Pathway and Malic Enzyme Reaction
What activates Fatty Acid Synthase? What is it’s overall reaction and main end product?
Insulin!
End product is 16-carbon saturated FA palmitic acid
Reaction
1 acetyl-CoA + 7 malonyl-CoA + 14 NADPH –> 1 palmitic acid + 7 CO2 + 14 NADP
