21.5. Lipid synthesis
Synthesis of fatty acids is catalyzed by fatty acid synthase which is a multifunctional enzyme. This enzyme is located in the cytoplasm which acts upon the acetyl CoA as a primer molecule. NADPH is used reducing agent in this reaction.
Fatty acid synthase enzyme catalyzes all the seven reactions of this process. It is a homodimer contains two identical peptide chains. Every reaction catalyzed by a specific enzyme. This enzyme has 3 domains – Domain one catalyze the condensation of acetyl CoA and malonyl CoA, Domain two catalyze the formation of final product of the process and Domain three catalyze the release of final product.
- Formation of Malonyl CoA – acetyl CoA is impermeable to mitochondrial membrane so it is converted to malonyl CoA. It is catalyzed by the enzyme actyl CoA carboxylase. It uses Mn+2 and biotin as a coactivator which donates a CO2 molecule and one ATP molecule.
- Now further process is catalyzed by the fatty acid synthase which have Cys-SH and Pan-SH as two arms of it. Both of these arms accepts acetyl CoA and Malonyl CoA respectively. Both arms acts as transacylase which removes CoA from both of the molecules and Acyl Carrier Protein is attached.
- Condensation – As acetate attacks on malonate to form acetoacetyl ACP which is catalyzed by Keto acyl synthase. Single molecule of CO2 is lost in this reaction and the acetoacetyl ACP remain attached to Pan SH.
- Reduction – NADPH is converted to NADP+ and reaction is catalyzed by B-keto acyl reductase.
- Dehydration – single water molecule is removed by b-OH-butyryl dehydratase.
- Reduction – NADPH is used and catalyzed by enoyl reductase.
- Thiolysis – it is the final reaction of a molecule. If synthesizing lipid is to be larger molecule than all of these steps are repeated. SH bond is cleaved by thioesterase enzyme and ACP molecule is release from the molecule and final product is released from the enzyme.
For the synthesis of a 16 carbon molecule i.e. palmitic acid, final reaction will be –
So the overall reaction will be
21.6. Regulation of fatty acid synthesis
Allosteric Control – This is sudden or short term control in which enzymes can be controlled by covalent modification.
Hormonal Control – hormones affect the enzyme and regulate the process of lipid synthesis.
- Acetyl CoA Carboxylase – this enzyme catalyze the rate limiting step of this process. It is regulated by phosphorylation and dephosphorylation by protein kinases. Citrate acts as activator for this enzyme.
- Glucagon – it inhibits glycolysis by inactivating PFK enzyme so thereby decrease in the synthesis of citrate in Krebs cycle. So decrease in citrate inactivates the acetyl CoA carboxylase and reduces fatty acid synthesis.
- Insulin – it acts in contrast to glucagon. It enhances citrate there by activating AcetylCoA carboxylase and more lipid synthesis.