Lipid Classification, Transport & Digestion.

• General characteristics of lipids:

  • Heterogeneous group of hydrophobic compounds
  • Soluble in organic solvents and nearly insoluble in water
  • Some lipids contain non-lipid groups such as sialic, phosphoryl, amino or sulphate groups, giving them an affinity for both water and organic solvents
  • Important in the formation of biological membranes
  • Lipids with amphibolic characteristics include phospholipids and glycolipids
• Fatty acids:

  • General chemical formula: R-COOH
  • Classified based on the number of carbon atoms present: short chain (2 to 4), medium chain (6 to 10), long chain (12 to 26)
  • Classified further based on degree of saturation: saturated fatty acids (no double bonds), monounsaturated fatty acids (one double bond), polyunsaturated fatty acids (more than one double bond)
• Cis vs Trans Fatty Acids:

  • Cis fatty acids occur naturally
  • Trans fatty acids occur during hydrogenation reactions (unhealthy)
• Fatty acid labeling:

  • Can be labeled from the carboxyl terminal (∆-numbering system) or methyl terminal (n- or w-numbering system)
  • Example: Linoleic acid (C18:2, D9,12) or (C18:2; w6)
• Lipid classes:

  • Triacylglycerols are carboxylic acid triesters of glycerol, major source of biochemical energy
  • Triglycerides: fats and oils, glycerol + 3 fatty acids connected by ester bonds
  • Phospholipids: glycerophospholipids are triesters of glycerol containing charged phosphate diester groups, abundant in cell membranes
  • Sphingomyelins: amides derived from sphingosine, contain charged phosphate diester groups, essential to cell membrane structure
  • Glycolipids: different amides derived from sphingosine, contain polar carbohydrate groups, recognized by intracellular messengers
• Cholesterol:

  • Steroid alcohol with 27 carbon atoms arranged in a tetracyclical sterane skeleton
  • Most important type of animal sterol and precursor of all steroids in humans
• Eicosanoids:

  • Derived from 20-carbon unsaturated fatty acids (eicosanoic acids)
  • Function as short-lived chemical messengers near their points of synthesis
  • Prostaglandins and leukotrienes are two classes of eicosanoids
• Prostaglandin E2 (PGE2), Thromboxane A2 (TXA2), and Leukotriene A4 (LTA4) are two classes of eicosanoids found in leukocytes
• The main pathway of lipid digestion in the gastrointestinal tract involves the hydrolysis of ester linkages at positions 1 and 3, forming 2-Monoacylglycerols and 2 free fatty acids in the small intestine
• Tongue lipase and gastric lipase preferentially digest triglycerides with short or middle-chain fatty acids (12 and less than 12 carbon atoms), important for lipid digestion in infants and small children
• Pancreatic lipase, synthesized and secreted with co-lipase, requires an optimal pH of 6-8 achieved by neutralizing stomach acid with alkaline bile for lipid digestion in the small intestine
• Bile acids emulsify lipids for digestion in the small intestine, while pancreatic phospholipase A2 and esterase hydrolyze phospholipids and cholesterol esters, respectively
• Lipoproteins transport lipids in plasma in macromolecular complexes, with non-polar lipids in the core and more polar lipids near the surface, containing specific proteins called apolipoproteins
• Lipoproteins are classified by density, reflecting size, with different subclasses like chylomicrons, VLDL, IDL, LDL, HDL, and VHDL based on their lipid/protein ratio
• Enzymes involved in lipoprotein metabolism include lipoprotein lipase (LPL) located on blood capillary walls, hepatic lipase (HL) important for lipoprotein metabolism, and lecithin:cholesterol acyltransferase (LCAT) synthesized in the liver
• Apolipoproteins like apoA-I, apoA-II, apoA-IV, apoB-48, apoB-100, apoC-I, apoC-II, apoC-III, apoD, and apoE are associated with different lipoproteins and have various functions in lipid metabolism
• Familial hypercholesterolemia (type IIa) is characterized by a defect in the LDL receptor or the receptor-binding region of apoB, leading to elevated LDL levels and increased risk of cardiovascular diseases
• Lipoproteins are spherical structures made up of lipids and proteins that help keep fats dissolved in the blood and transport them to and from tissues
• Major types of lipoproteins:

  • Exogenous transport pathway: chylomicrons, chylomicron remnants
  • Endogenous transport pathway: very low-density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), low-density lipoproteins (LDLs)
  • Reverse cholesterol pathway: high-density lipoproteins (HDLs)
• Chylomicrons, chylomicron remnants, VLDLs, IDLs, and LDLs have pro-atherogenic properties, increasing the risk of atherosclerosis, while HDLs are anti-atherogenic, decreasing the risk of atherosclerosis
• Lipoproteins have a hydrophobic core containing triglycerides and cholesterol esters, surrounded by a hydrophilic layer of phospholipids, proteins, and free cholesterol
• Lipoproteins are divided based on their density, with greater protein content and lower fat content leading to higher density
• Chylomicrons are the largest and least dense lipoproteins, consisting mainly of triglycerides, followed by VLDLs, LDLs, and HDLs, which are the smallest and most dense
• Apolipoproteins are proteins that help dissolve triglycerides and cholesterol in the blood, with different types serving specific functions such as guiding formation, providing structural support, acting as ligands for receptors, and activating or inhibiting enzymes