Chapter 5

• J. L. W. Thudichum is the first to define the chemical composition of the brain, including several lipids, in 1884
• About half of the brain tissue's dry weight consists of lipids, indicating their crucial role in neurochemistry.
• Lipid modification of proteins is the key mechanism for modulating the activity of trophic factors and receptors
• Lipids have a critical role in nervous system structure and function, contributing to synaptic complexes, myelin, and signaling pathways
• Plasmalogens are vinyl ether-linked phospholipids that is included in many other specialized phospholipids that enriches the brain
• Brain lipids primarily functions to form biomembranes and lipid-mediated signal transduction
• Membrane lipids (polyphosphoinositides & phosphatidylcholine) also have important functions in signal transduction across biological membranes
• Cholesterol & sphingolipids play a central role in formation of lipid rafts, which function in protein trafficking and signaling at the cell surface
• All membrane lipids are amphipathic molecules with a small polar, or hydrophilic, moiety and a large nonpolar, or hydrophobic, moiety.
• The parts of molecules that dislike water (hydrophobic regions) don't bond with water. Instead, they come together outside of water by weak attractions like Van der Waals forces. Because of this behavior, phospholipids naturally arrange into micelles or bilayers. In this arrangement, the water-loving (hydrophilic) parts of the molecule face the water, while the water-averse (hydrophobic) parts interact with each other in a "tail-to-tail" fashion.
• The hydrophobic components of many lipids consist of either isoprenoids or fatty acids and their derivatives
• Some substances that dissolve in lipid solvents, like certain proteins in myelin, aren't considered lipids because they're made of hydrophobic polypeptides.
• Isoprenoids are made of branched-chain units and include sterols like cholesterol.
• Lipids are defined by both their physical properties and their chemical makeup.
• Isoprenoids have the unit structure of a five-carbon branched chain
• Isoprenoid units have the formula C5H8 and these are used as the building blocks for the most abundant sterols in the brain.
• Brain fatty acids are long-chain carboxylic acids that may contain one or more double bonds
• The brain contains a variety of straight-chain monocarboxylic acids, with an even number of carbon atoms ranging from C12 to C26.
• Glycerolipids (complex lipids) are derivatives of glycerol and fatty acids
• The notation sn refers to stereochemical numbering, with the secondary hydroxyl group of glycerol at C-2 shown on the left, that is, the l-configuration of Fischer’s projection, and the phosphate at C-3.
• 1,2-diacyl-sn-glycerol (DAG)
• In sphingolipids (complex lipids), the long-chain aminodiol sphingosine serves as the lipid backbone. It resembles a monoradyl glycerol but has asymmetric carbons at both C-2 and C-3.
• Cardiolipin (CL) is a complex mitochondrial-specific phospholipid that regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. CL is essential for efficient oxidative energy production and mitochondrial function.
• Chromatography and mass spectrometry are employed to analyze and classify brain lipids
• The lipids from brain are generally extracted with a mixture of chloroform and methanol using variations of a method
• Acetyl coenzyme A is the precursor of both cholesterol and fatty acids
• The hydrophobic chains of lipids, that is, fatty acids and isoprenoids, are biosynthesized from the same two-carbon donor, acetyl coenzyme A (acetyl-CoA), with differences in condensation leading to different products.
• Fatty acids are biosynthesized via elongation of C2 units.
• Phosphatidic acid is the precursor of all glycerolipids
• Phospholipid biosynthesis is linked to glycolysis through the use of dihydroxyacetone phosphate (DHAP), formed from sn-glycerol-3-phosphate (Gro-3-P) via its reduction by NADH, catalyzed by glycerophosphate dehydrogenase.
• Sphingolipids are biosynthesized by adding head groups to the ceramide moiety
• Sphinganine, also termed dihydrosphingosine, is biosynthesized by a decarboxylating condensation of serine with palmitoyl-CoA to form a keto intermediate, which is then reduced by NADPH
• Ceramide is the precursor of all sphingolipids; sphingomyelin is formed by a reaction that transfers the head group of PtdCho to ceramide to form sphingomyelin and DAG
• genes coding for a number of lipid hydrolytic enzymes have been identified and cloned
• Lipids are transported between membranes. Lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis.
• Membrane lipids may be asymmetrically oriented.
• Some proteins are bound to membranes by covalently linked lipids. A number of membrane-bound proteins are covalently linked with various lipids, which promotes association of the protein with the lipid bilayer.
• Many lipids have multiple (both structural and regulatory) roles in the cell.