Ketone body metabolism

• The ketone bodies are produced mainly by the liver during periods when carbohydrate intake is low or insulin levels are low.
• 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.
• In general, the presence of double bonds decreases the melting temperature (Tm) of a fatty acid, while increasing the chain length increases the Tm.
• Acetyl CoA carboxylase activity is regulated by Palmytoil CoA Citrate.
• The first step going to fatty acid synthesis is an irreversible reaction.
• Fatty Acid Synthase is a multifunctional enzyme in eukaryotes.
• Fatty acid synthesis steps include Condensation, Reduction, Dehydration, and Reduction.
• 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.
• 4'-Phosphopantetheine, a derivative of the vitamin pantothenic acid, carries acyl units on its terminal thiol (–SH) group during fatty acid synthesis.
• Malonyl CoA inhibits Carnitine acyl transferase I (CAT I).
• The coenzyme in fatty acid synthesis is biotin, which is covalently bound to a lysyl residue of the carboxylase.
• In every four steps of fatty acid synthesis, 2C are added to the fatty acid.
• FAS uses NADPH as the electron donor and uses two enzyme-bound -SH groups as activating groups.
• Fatty acid synthesis is catalyzed by fatty acid synthase (FAS).
• FAS I in vertebrates and fungi is the enzyme that catalyzes the first step of fatty acid synthesis.
• The first product in the cytosol for fatty acid synthesis is malonyl-CoA.
• FAS catalyzes a repeating four-step sequence that elongates the fatty acyl chain by two carbons at each step.
• Beta-oxidation stops when Acetyl-CoA is present.
• It also is a component of CoA Transfer onto the enzyme.
• 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.
• Two fatty acids are dietary essentials in humans because of our inability to synthesize them: linoleic acid, which is the precursor of ω-6 arachidonic acid, the substrate for prostaglandin synthesis, and α-linolenic acid, the precursor of other ω-3 fatty acids important for growth and development.
• Omega-3 Fatty Acids contain a double bond at the ω-3 position.
• Fish oil and cold water fish (Cod, Somon) are sources of Omega-3 Fatty Acids.
• The first step in de novo fatty acid synthesis is the transfer of acetate units from mitochondrial acetyl CoA to the cytosol.
• Acetyl groups pass out of the mitochondrion as citrate; in the cytosol they are delivered as acetyl-CoA for fatty acid synthesis.
• Arachidonic acid (20:4 Δ5, 8, 11, 14 ) is produced in Mammals from Linoleic acid.
• A large proportion of the fatty acids used by the body is supplied by the diet.
• Fatty acid synthesis, triglyceride synthesis, phospholipid synthesis, and cholesterol synthesis are all part of structural lipids (membrane lipids) and storage lipids.
• The CoA portion of acetyl CoA, cannot cross the inner mitochondrial membrane; only the acetyl portion enters the cytosol.