BCH210H1 Lecture Notes - Lecture 37: Acetyl-Coa Carboxylase, Malonyl-Coa, Fatty Acid Synthase

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BCH210 Lecture 31 fat synthesis
Insulin
- Insulin is secreted in response to increased blood glucose
- Glucose is first broken down to produce ATP which is required for anabolic pathways
- Glucose is the stored as glycogen
- Glucose can be also used to synthesize fatty acids
- Amino acids are used to produce acetyl CoA which acts as a amphibolic intermediate
- Acetyl CoA is converted into fatty acids
Stages in fatty acid synthesis
- It takes place in the cytoplasm
- Export of mitochondrial acetyl CoA to the cytoplasm for fat synthesis
- Conversion of acetyl CoA to malonyl CoA via carboxylation reaction by acetyl-CoA
carboxylase (ACC)
o CO2 is added onto acetyl CoA
- Use of malonyl CoA to form fatty acid chains by fatty acid synthase (FAS)
o Decarboxylation reaction is spontaneous and drives the reaction forward
Import and export differ
- Remember that CoA cannot cross the inner mitochondrial membrane
- Acetyl CoA and pyruvate in the matrix are converted to citrate via the citric acid cycle by
citrate synthase
- Citrate can then be exported out to the cytoplasm where it is converted back to acetyl
CoA and Pyruvate
- Pyruvate can be used again by bringing into the matrix and use it to produce citrate
o Pyruvate is regenerated a long with the production of NADPH
Anabolic fatty acid synthesis
- Acyl chain synthesis occurs in the cytoplasm
- 2 enzymes are needed
o Acetyl CoA carboxylase
Committed and regulated step of fatty acid synthesis
Coverts acetyl CoA to malonyl CoA, activated 2 carbon carrying precursor
for fatty acid synthesis
Uses ATP
o Fatty acid synthase
Uses NADPH
Reciprocal regulation of fats
- When fat synthesis is ON, fat degradation is OFF
- The product of ACC inhibits acyl chain import
- Malonyl CoA allosterically inhibits CATI and shuts down the car I time shuttle
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