Fatty acid synthesis template

Acetyl-CoA → malonyl-CoA (acetyl-CoA carboxylase, biotin, ATP); the FAS cycle of condensation (−CO₂), reduction (NADPH), dehydration and reduction (NADPH) from acetoacetyl-ACP to butyryl-ACP, then six more cycles and the thioesterase to palmitate; stoichiometry 8 acetyl-CoA + 7 ATP + 14 NADPH.

What the template shows

• In the cytosol, acetyl-CoA carboxylase makes malonyl-CoA and fatty acid synthase adds two carbons per cycle until palmitate (C₁₆)
• Committed step: carboxylation (acetyl-CoA carboxylase, ACC)
• Biotin carries CO₂ (as carboxybiotin) from HCO₃⁻ to acetyl-CoA; R = CoA
• acetyl-CoA
• malonyl-CoA
• Fatty acid synthase, one turn (1): condensation and the first reduction
• R = Cys-SH of the ketoacyl synthase (KS), R′ = phosphopantetheine arm of the acyl carrier protein (ACP)
• acetyl-KS (primer)
• malonyl-ACP
• acetoacetyl-ACP
• D-3-hydroxybutyryl-ACP
• One turn (2): dehydration and the second reduction
• trans-Δ²-butenoyl-ACP
• butyryl-ACP (C₄)
• Six more turns, then the thioesterase releases palmitate
• Each turn adds C₂ from malonyl-ACP and uses 2 NADPH; the chain is released at C₁₆
• butyryl-ACP
• Palmitate: 8 acetyl-CoA + 7 ATP + 14 NADPH + 14 H⁺ → palmitate + 8 CoA + 7 ADP + 7 Pᵢ + 14 NADP⁺ + 6 H₂O (7 malonyl-CoA, each turn releasing the CO₂ ACC added).
• Unlike β-oxidation: cytosol not matrix, ACP not CoA, D-3-hydroxyacyl not L, NADPH not NAD⁺/FAD. NADPH comes from the pentose phosphate pathway and malic enzyme.
• Acetyl-CoA leaves the mitochondrion as citrate (ATP-citrate lyase in the cytosol); citrate activates ACC, palmitoyl-CoA inhibits it and AMPK phosphorylation switches it off.
• Malonyl-CoA blocks carnitine palmitoyltransferase I, so new fatty acids are not oxidised at the same time. Acids are drawn neutral.

Drawn with 89 atoms, 6 arrows, 4 shapes – every one editable in MolDraw.

Sources

• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 21 Textbook
• Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019 Textbook
• Voet & Voet, Biochemistry, 4th ed., Wiley 2011 Textbook
• Wakil, Titchener & Gibson, Biochim. Biophys. Acta 1958, 29, 225 Original paper
• Knappe, Ringelmann & Lynen, Biochem. Z. 1961, 335, 168 Original paper