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BIOC/DENT/PHCY 230 LECTURE 8

BIOC/DENT/PHCY 230 LECTURE 8. Transport and delivery of dietary lipids. dietary triacylglycerol (TAG) and cholesterol are delivered to target tissues by lipoproteins the four main lipoproteins are: chylomicrons VLDL LDL HDL.

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BIOC/DENT/PHCY 230 LECTURE 8

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  1. BIOC/DENT/PHCY 230 LECTURE 8

  2. Transport and delivery of dietary lipids • dietary triacylglycerol (TAG) and cholesterol are delivered to target tissues by lipoproteins • the four main lipoproteins are: chylomicrons VLDL LDL HDL

  3. each lipoprotein has a characteristic combination of lipids and apoproteins • chylomicrons and VLDL are the primary transporters of TAGs to target tissues • LDL and HDL are the primary transporters of cholesterol

  4. Structure of a general lipoprotein

  5. Lipoprotein lipase liberates free fatty acids from TAGs Chylomicrons and VLDLs have apoprotein CII, which anchors the lipoprotein to lipoprotein lipase

  6. Fatty acid synthesis • excess carbohydrate is converted to fatty acids and TAGs • fatty acid synthesis occurs in the cytoplasm of a variety of cell types • synthesis of fatty acids is based around acetyl-CoA • acetyl-CoA is a precursor for malonyl-CoA • it is in the form of malonyl-CoA that most carbons are introduced into fatty acid synthesis

  7. Synthesis of malonyl-CoA

  8. In vertebrates: • fatty acid synthesis is catalysed by a multi functional enzyme, fatty acid synthase • fatty acid synthase contains all the enzyme activities required for the remainder of fatty acid synthesis

  9. Synthesis of Acetyl-ACP and Malonyl-ACP Acetyl-CoA and malonyl-CoA are attached to an acyl carrier protein (ACP)

  10. Initiation of fatty acid synthesis

  11. b-oxidation synthesis NADP+ + H+ NADP+ + H+ NADPH NADPH

  12. Elongation continues with the addition of malonyl-CoA

  13. 8 acetyl-CoA + 14 NADPH + 7ATP palmitate + 14 NADP+ + 8 CoA + 7ADP + 7 Pi + 6H2O Overall equation for the synthesis of palmitate (16:0)

  14. Synthesis of TAGs • fatty acids are added onto a glycerol backbone • glycerol -3- phosphate can be derived from: DHAP (glycolysis) phosphorylation of glycerol by glycerol kinase

  15. Regulation of fatty acid synthesis • fatty acids synthesis can be regulated in a number of ways • acetyl-CoA carboxylase represents a major control point

  16. inactive acetyl-CoA carboxylase is found as a dimer • polymerisation activates the enzyme inactive dimer - + acetyl-CoA citrate insulin palmitoyl-CoA glucagon active polymer

  17. glucose Excess citrate is shuttled to the cytoplasm

  18. NADPH supplies the reducing power for fatty acid biosynthesis NADH NADPH

  19. NADPH is generated by the Pentose Phosphate Pathway

  20. The take home message • dietary lipids are delivered to target tissues by lipoproteins • excess fuels can be converted fatty acids • fatty acid synthesis has many features in common with b-oxidation • acetyl-CoA carboxylase represents a major control point for fatty acid synthesis • reducing power in the form of NADPH is supplied by the pentose phosphate pathway

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