V. De novo Synthesis of Fatty Acids
Enzymes and Isolated Reactions: Acetyl CoA carboxylase
Acetyl CoA carboxylase has three important features.
- It contains the prosthetic group, biotin.
- The enzyme, using its biotin prosthetic group as a carrier, transfers CO2 from bicarbonate to the acetyl group.
- Biotin is not synthesized in humans, and is an essential
- The carboxylation reaction is driven to completion by
hydrolysis of ATP.
- The enzyme catalyzes the rate-limiting reaction for fatty acid
synthesis, and is under tight short-term control.
- It is down-regulated by:
- palmitoyl CoA (endproduct regulation).
- phosphorylation of the enzyme (through a glucagon-cAMP cascade).
- It is up-regulated by:
- citrate (allosteric)
- dephosphorylation of the enzyme (influenced by the insulin/glucagon ratio).
To summarize, it is controlled both allosterically (citrate, palmitoyl CoA) and by covalent modification (phosphorylation/dephosphorylation).