1. Lipid Metabolism Dietary Lipid Reactions Lecture 1 of 5 Jim Littlejohn 11/20/03 Texas A+M Health Sciences Center: College of Medicine

2. Lipid Types Vitamins A, D, E, K Vitamins A, D, E, K Phospholipids, Sphingolipids, Glycolipids Phospholipids, Sphingolipids, Glycolipids Fatty Acids and Triacylglycerols Fatty Acids and Triacylglycerols Cholesterols Cholesterols Lipoproteins Lipoproteins VLDL, LDL, HDLVLDL, LDL, HDL ChylomicronsChylomicrons

3. Fatty Acids hydrophilic vs. hydrophobic hydrophilic vs. hydrophobic saturated vs. unsaturated saturated vs. unsaturated Essential fatty acids Essential fatty acids PUFA’s (position of first double bond from methyl end)PUFA’s (position of first double bond from methyl end) Ω-3, Ω-6 Fatty AcidsΩ-3, Ω-6 Fatty Acids Humans can only add from carboxyl to 9 th carbonHumans can only add from carboxyl to 9 th carbon Plants can add between 9 th and Ω carbonPlants can add between 9 th and Ω carbon Mmmm….Salmon!Mmmm….Salmon! Nomenclature Nomenclature Described in # of bonds and position of double bondsDescribed in # of bonds and position of double bonds arachidonic acid 20:4 Δ 5,8,11,14arachidonic acid 20:4 Δ 5,8,11,14 cis vs. trans cis vs. trans look at your margarine container!look at your margarine container!

4. Triglycerides Digested in Small Intestine Digested in Small Intestine needs bile salts (cholesterol skeleton)needs bile salts (cholesterol skeleton) our only way to excrete cholesterol!our only way to excrete cholesterol! most are reabsorbedmost are reabsorbed Pancreatic Lipase Pancreatic Lipase breaks into 2-monoacylglycerols and free fatty acids (FFA’s)breaks into 2-monoacylglycerols and free fatty acids (FFA’s) Absorbed into Intestinal Epithelium Absorbed into Intestinal Epithelium Activate FFA’s with CoASH Activate FFA’s with CoASH Fatty Acid CoA SynthetaseFatty Acid CoA Synthetase reassemble triacylglyceridereassemble triacylglyceride

6. Chylomicrons and VLDL Major carriers of triacylglycerols and cholesterol Major carriers of triacylglycerols and cholesterol Chylomicrons Chylomicrons made in intestinal epitheliamade in intestinal epithelia enter lymph to bloodenter lymph to blood The least protein and most triacylglycerol of the lipoproteinsThe least protein and most triacylglycerol of the lipoproteins Digested in capillaries Digested in capillaries remnants taken up by liverremnants taken up by liver Lipoprotein LipaseLipoprotein Lipase VLDL converted to IDL… VLDL converted to IDL…

8. Fatty acid synthesis Occurs in Liver Occurs in Liver Acetyl CoA usedAcetyl CoA used add in units of 2 carbonsadd in units of 2 carbons Fatty Acid Synthase Complex (FAS) Fatty Acid Synthase Complex (FAS) Palmitate, a 16 carbon saturated FAPalmitate, a 16 carbon saturated FA Converted to other lengths and saturation states after releaseConverted to other lengths and saturation states after release Packaged in VLDL and sent to blood Packaged in VLDL and sent to blood LDL produced from VLDL and provides cholesterol to various tissuesLDL produced from VLDL and provides cholesterol to various tissues HDL picks up cholesterol from cells back to liverHDL picks up cholesterol from cells back to liver

10. Triacylglycerol Synthesis Acetyl CoA Acetyl CoA converted in cytosol to malonyl CoAconverted in cytosol to malonyl CoA has to get out of matrix!has to get out of matrix! Pyr  OAA  Citrate  OAA  Malate  Malonyl CoA Pyr  OAA  Citrate  OAA  Malate  Malonyl CoA NADPH produced by Pentose Phosphate Pathway and Malic EnzymeNADPH produced by Pentose Phosphate Pathway and Malic Enzyme Lipogenesis Lipogenesis esterification occurs mainly in the liveresterification occurs mainly in the liver reassembled in intestinal cells and adipocytes!reassembled in intestinal cells and adipocytes!

12. Transport through the Blood Chylomicrons Chylomicrons lymph  blood  capillaries  liverlymph  blood  capillaries  liver endocytosed and degraded in lysozomeendocytosed and degraded in lysozome least dense, most triacylglycerolleast dense, most triacylglycerol VLDL VLDL used by adipocytes turned into IDLused by adipocytes turned into IDL IDL IDL more dense than VLDL, less than ½ triacylglycerolmore dense than VLDL, less than ½ triacylglycerol LDL LDL less triacylglycerol and more protein (even more dense)less triacylglycerol and more protein (even more dense) HDL HDL lowest triacylglycerol and most proteinlowest triacylglycerol and most protein

13. Adipocytes Hormone Sensitive Hormone Sensitive Lipases activated by glucagon to release energy stored in triacylglycerolLipases activated by glucagon to release energy stored in triacylglycerol Insulin stimulated uptake of glucose Insulin stimulated uptake of glucose adipocytes lack glycerol kinaseadipocytes lack glycerol kinase DHAP  Glycerol-3-PhosphateDHAP  Glycerol-3-Phosphate Metabolic intermediate Metabolic intermediate Lipoprotein Lipase Lipoprotein Lipase Attached to membranes of cells in the walls of capillariesAttached to membranes of cells in the walls of capillaries Apolipoprotein C II activates enzymeApolipoprotein C II activates enzyme

15. Oxidation of FA’s Mainly B-oxidation Mainly B-oxidation Transport into mitochondria Transport into mitochondria carnitine carrier systemcarnitine carrier system even chain completely converted to Acetyl CoAeven chain completely converted to Acetyl CoA odd chain fatty acids produce propionyl CoA (used to make glucose)odd chain fatty acids produce propionyl CoA (used to make glucose) Beware the trans-fatty acid! Beware the trans-fatty acid!