Lipid Biosynthesis
Fatty acid biosynthesis and breakdown occur in different pathways, catalysed by different
sets of enzymes, and in different parts of the cell.
Biosynthesis of fatty acids requires a 3C intermediate called malonyl-CoA.
Fatty acid oxidation produces acetyl-CoA and reducing power (NADH, FADH2), and takes
place in the mitochondria.
Anabolism of fatty acids requires acetyl-CoA and malonyl-CoA, as well as reducing power
from NADPH, and takes place in the cytosol in animals and chloroplast in plants.
Acetyl-CoA is carboxylated with the help of HCO3- (bicarbonate), which is the soluble
source of CO2.
Acetyl-CoA carboxylase is responsible for this reaction and is composed of either a
trimeric or monomeric structure.
Biotin, covalently linked to Lys, carries CO2 in the carboxylation reaction.
Acetyl-CoA carboxylase reaction is irreversible and occurs in two steps, where CO2 binds
to biotin, which is then activated by attachment to the N in the ring of biotin, producing
carbamoyl.
CO2 then attaches to acetyl-CoA to produce malonyl-CoA.
Fatty acid synthase (FAS) catalyzes a repeating four-step sequence for the elongation of
fatty acyl chains.
FAS uses NADPH as the electron donor and two enzyme-bound -SH groups as activating
groups.
There are different FAS systems: FAS I in vertebrates and fungi, and FAS II in plants and
bacteria.
The four steps in FAS are repeated 7 times to produce palmitic acid (16:0).
Elongation of palmitate occurs in the smooth ER and mitochondria, while desaturation
(introduction of double bonds) occurs in the smooth ER.
Palmitate is an essential fatty acid that cannot be synthesized by mammals and must be
obtained from the diet.
Synthesized fatty acids can be incorporated into triacylglycerols or phospholipids.
Cholesterol biosynthesis starts with acetate (Acetyl-CoA) and goes through four stages to
produce cholesterol and other natural lipids.
Cholesterol has various fates, including membrane biosynthesis, bile acids and salts,
cholesteryl esters, storage in the liver, steroid hormone precursor, and vitamin D precursor.