Fatty acid metabolism

• Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules.
• Body lipids are generally found compartmentalized due to their insolubility in aqueous solutions, such as in the case of membrane-associated lipids or droplets of triacylglycerol in white adipocytes.
• Lipids are a major source of stored energy for the body, and they also provide the hydrophobic barrier that permits partitioning of the aqueous contents of cells and subcellular structures.
• Lipids serve additional functions in the body, for example, some fat-soluble vitamins have regulatory or coenzyme functions, and the prostaglandins and steroid hormones play major roles in the control of the body’s homeostasis.
• A fatty acid consists of a hydrophobic hydrocarbon chain with a terminal carboxyl group.
• At physiologic pH, the terminal carboxyl group (–COOH) ionizes, becoming –COO–.
• The anionic group has an affinity for water, giving the fatty acid its amphipathic nature (having both a hydrophilic and a hydrophobic region).
• Fatty acid chains may contain no double bonds—that is, saturated— or contain one or more double bonds—that is, mono- or polyunsaturated.
• When double bonds are present, they are nearly always in the cis rather than in the trans configuration.
• A monounsaturated fatty acid has one double bond, while a polyunsaturated fatty acid has two or more double bonds.
• The introduction of a cis double bond causes the fatty acid to bend or “kink” at that position.
• If the fatty acid has two or more double bonds, they are always spaced at three-carbon intervals.
• Acetyl CoA carboxylase activity is regulated by Palmytoil CoA Citrate.
• Fatty acid synthesis steps include Condensation, Reduction, Dehydration, and Reduction.
• The first step going to fatty acid synthesis is an irreversible reaction.
• FAS catalyzes a repeating four-step sequence that elongates the fatty acyl chain by two carbons at each step.
• Each FAS monomer is a multicatalytic polypeptide and the enzyme has seven different enzymatic activities plus a domain that covalently binds a molecule of 4'-phosphopantetheine.
• Fatty acid synthesis is catalyzed by fatty acid synthase (FAS).
• In every four steps of fatty acid synthesis, 2C are added to the fatty acid.
• FAS I in vertebrates and fungi.
• Malonyl CoA inhibits Carnitine acyl transferase I (CAT I).
• FAS uses NADPH as the electron donor and uses two enzyme-bound -SH groups as activating groups.
• The coenzyme in fatty acid synthesis is biotin, which is covalently bound to a lysyl residue of the carboxylase.
• It also is a component of CoA Transfer onto the enzyme.
• Fatty Acid Synthase is a multifunctional enzyme in eukaryotes.
• Beta-oxidation stops when Acetyl-CoA is present.
• 4'-Phosphopantetheine, a derivative of the vitamin pantothenic acid, carries acyl units on its terminal thiol (–SH) group during fatty acid synthesis.
• The first product in the cytosol for fatty acid synthesis is malonyl-CoA.
• In general, the presence of double bonds decreases the melting temperature (Tm) of a fatty acid, while increasing the chain length increases the Tm.
• Membrane lipids typically contain Long Chain Fatty Acid, and the presence of double bonds in some fatty acids helps maintain the fluid nature of those lipids.
• Malonyl CoA inhibits CPT-I, thus preventing the entry of long-chain acyl groups into the mitochondrial matrix.
• Fatty acids shorter than 12 carbons can cross the inner mitochondrial membrane without the aid of carnitine or the CPT system.
• Once inside the mitochondria, short- and medium-chain fatty acids are activated to their CoA derivatives by matrix enzymes, and are oxidized.
• After each two-carbon addition, reductions convert the growing chain to a saturated fatty acid of four, then six, then eight carbons, and so on.
• Elongation requires a system of separate enzymes rather than a multifunctional enzyme.
• Each step of β-oxidation is catalyzed by enzymes with chain-length specificity.
• The overall process of palmitate synthesis involves the fatty acyl chain growing by two-carbon units donated by activated malonate, with loss of CO2 at each step.
• The energy yield from the β-oxidation pathway is high.
• The β-keto group is reduced to an alcohol, then elimination of H2O creates a double bond, and the double bond is reduced to form the corresponding saturated fatty acyl group.
• The β-oxidation of a saturated fatty acid with an odd number of carbon atoms proceeds by the same reaction steps as that of fatty acids with an even number, until the final three carbons are reached.