CoachFatty acids are made in the cytosol from acetyl-CoA exported from the mitochondrion. Acetyl-CoA carboxylase, the regulated step, carboxylates it (one ATP) to malonyl-CoA; fatty acid synthase then adds two carbons at a time from malonyl-CoA to a growing chain, reducing each addition with two NADPH, until palmitate (C16) is released: 8 acetyl-CoA, 7 ATP and 14 NADPH per palmitate. Elongation and desaturation in the endoplasmic reticulum make the other acids; esterification with glycerol-3-phosphate (from triose phosphate) makes triglycerides. The pathway is not -oxidation reversed: different enzymes, a different compartment, malonyl-CoA instead of acetyl-CoA, NADPH instead of and NADH — and malonyl-CoA blocks the transport of fatty acids into the mitochondrion, so a cell does not make fat and burn it at the same time.
Examples
Example 16.8 (Fat from sugar)
A liver given more glucose than it can store as glycogen makes fat: glucose to pyruvate to acetyl-CoA (losing a third of the carbon as and gaining ATP), acetyl-CoA to palmitate at the cost of that ATP and of NADPH from the pentose phosphate pathway, palmitate to triglyceride shipped to adipose tissue. Some of the sugar’s energy is lost in the conversion; the rest is stored nine times more compactly than glycogen (Chapter 9). The reverse — fat to sugar — is impossible.