Fatty Acid De Novo Synthesis
| Rate-Limiting Enzyme: | Acetyl-CoA Carboxylase (ACC) |
| Cellular Location: | Cytosol (Mainly liver, lactating mammary glands, and adipose tissue) |
| Major Co-factors Required: | Biotin (Vitamin B7), ATP, NADPH (From HMP Shunt & Malic Enzyme) |
| End-Product of Multi-Enzyme: | Palmitate (16-carbon saturated fatty acid) |
High-Yield Core Realities:
- The Citrate Shuttle: Acetyl-CoA is locked in the mitochondrial matrix and cannot cross the inner membrane directly. When TCA cycle activity slows down due to high energy charges, Citrate built up inside the matrix is exported to the cytosol via the tricarboxylate transporter. Cytosolic ATP-Citrate Lyase then cleaves it back into Acetyl-CoA and Oxaloacetate (OAA).
- ACC Regulation Dynamics: Citrate drives allosteric polymerisation and activation of ACC, shifting synthesis into gear. Conversely, the final pathway product, Palmitoyl-CoA, triggers depolymerisation and inactivation.
- Covalent Hormonal Control: Insulin upregulates fatty acid synthesis by activating a protein phosphatase that leaves ACC in its active dephosphorylated state. Glucagon and Epinephrine trigger AMP-activated protein kinase (AMPK) and PKA, phosphorylating ACC to shut it off.
- Fatty Acid Synthase (FAS) Mechanics: FAS is a massive homodimeric multifunctional enzyme containing an Acyl Carrier Protein (ACP) arm that requires phosphopantetheine (Vitamin B5). It builds palmitate 2 carbons at a time, utilizing Malonyl-CoA as the recurring carbon donor and consuming 2 NADPH molecules per elongation cycle.