7 11 15 Biochemistry 401 Lecture 28 Lipid Metabolism TAGs and Membrane Lipids Triacylglycerol Synthesis Phospholipid Synthesis Glycolipid Synthesis Aberrant Lipid Synthesis and Disease Membrane lipids Hydrophilic Head Groups Hydrophobic Fatty Acid Tails Hydrophilic Head Groups http swift cmbi ru nl gv students mtom phospholipid membranes gif Three Classes of Membrane Lipids Sterols Cholesterol Phospholipids Phosphate Alcohol head group One or more fatty acids Platform either glycerol or sphingosine Glycolipids One or more sugar head group One or more fatty acids Platform sphingosine in animals Glycerol in some organisms plants 1 7 11 15 Three Classes of Membrane Lipids Sterols Cholesterol Phospholipids Phosphate Alcohol head group One or more fatty acids Platform either glycerol or sphingosine Terminal OH Glycolipids One or more sugar head group One or more fatty acids Platform sphingosine in animals Glycerol in some organisms plants Three Classes of Membrane Lipids Sterols Cholesterol Phospholipids Phosphate Alcohol head group One or more fatty acids Platform either glycerol or sphingosine Glycolipids One or more sugar head group One or more fatty acids Platform sphingosine in animals Glycerol in some organisms plants Head group Sugar Sugar Sphingosine Fatty acid Glycerol Fatty acid Alcohol PO43Sphingosine Fatty acid Fatty acid Fatty acid Glycerol Platform Fatty acid Alcohol PO43 2 7 11 15 O O O Phosphatidate Activated diacylglycerol precursor Triacylglycerol Phosphoglycerolipids Phosphatidate I de novo 1 DHAP 2 Glycerol II Salvage Liver Phosphatidate I de novo 1 DHAP 2 Glycerol II Salvage 3 7 11 15 Liver Phosphatidate I de novo 1 DHAP 2 Glycerol II Salvage Where have we seen this before 4 7 11 15 Phosphatidate I de novo 1 DHAP reduction of DHAP then acylation 2 Glycerol phosphorylation then acylation II Salvage phosphorylation of diacylglycerol H In adipose tissue Triacylglycerol catabolised To free fatty acids glycerol Glycerol travels in blood to liver In liver cells Glycerol kinase produces glycerol 3 P 200 600 times more activity Phosphatidate I de novo 1 DHAP reduction of DHAP then acylation 2 Glycerol phosphorylation then acylation II Salvage phosphorylation of diacylglycerol 5 7 11 15 Enzyme Glycerol Phosphate Acyltransferase Fatty Acid Acylation Phosphatidate I de novo 1 DHAP reduction of DHAP then acylation 2 Glycerol phosphorylation then acylation II Salvage phosphorylation of diacylglycerol Phosphate Hydrolysis Triacylglycerol Synthesis Addition of a third activated fatty acid Acylation Enzyme Triacylglycerol synthetase complex TAG made in liver transported To muscles Energy production To adipose tissue Storage 6 7 11 15 Phosphatidate I de novo 1 DHAP reduction of DHAP then acylation 2 Glycerol phosphorylation then acylation II Salvage phosphorylation of diacylglycerol Alcohols typically used as head groups The names of glycerophospholipids generally begin with phosphatidyl and then the name of the head group that it contains such as phosphatidylinositol Activation of Phosphatidate For Glycerophospholipid Synthesis Activating phosphatidate for addition of a head group to C3 Reaction is driven forward by hydrolysis of pyrophosphate CTP is used in this activation 7 7 11 15 Alcohol addition to activated phosphatidate Activation of the head group by CTP Ethanolamine activated in 2 steps 1 Phosphorylation by ATP 2 Activation by CTP Driven forward by release and hydrolysis of PPi Produces CDP ethanolamine 2 Pi 3 Transfer of the phosphorylethanolamine head group This head group is added to diacylglycerol to make phosphatidylethanolamine CMP is released as a leaving group Phosphatidylcholine Synthesis From Phosphatidyl Ethanolamine Tri methylation of phosphatidylethanolamine Requires 3 S adenosyl Methionine SAM SAM is a carrier of activated methyl groups 8 7 11 15 Cardiolipin Made from addition of an activated phosphatidylglycerol as a head group Cardiolipin is found in the inner MT membrane and is important for organization of the ETC components Sphingolipid Production Ceramide Synthesis Reduction Fatty acid CoA Fatty Acid added Oxidation Activated Glucose UDPglucose Phospholipid Glycolipid 9 7 11 15 Tay Sachs 10 7 11 15 Surfactant Deficiency Disorder Respiratory Distress Syndrome Greater thermostability Branched hydrocarbon chain linkage Hydrophilic Many span the membrane Ether Hydrophobic Archaeal lipid Hydrophilic 11 7 11 15 This marks the end of Lecture 28 have a great day 12
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