7/11/15%1%Biochemistry401Lecture 28 Lipid Metabolism:TAGs and Membrane Lipids Triacylglycerol Synthesis Phospholipid Synthesis Glycolipid Synthesis Aberrant Lipid Synthesis and Diseasehttp://swift.cmbi.ru.nl/gv/students/mtom/phospholipid_membranes.gif Hydrophilic Head Groups Hydrophilic Head Groups Hydrophobic Fatty Acid Tails 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) Three Classes of Membrane Lipids:7/11/15%2% 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) Three Classes of Membrane Lipids: Terminal OH! 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) Three Classes of Membrane Lipids: Fatty acidFatty acidGlycerol!PO43-AlcoholFatty acidSphingosinePO43-AlcoholFatty acidSphingosineFatty acidFatty acidGlycerol!SugarSugarHead group!Platform!7/11/15%3%O OO!Phosphatidate: Activated diacylglycerol precursor !• Triacylglycerol !• Phosphoglycerolipids!Phosphatidate: I. de novo: 1) DHAP: 2) Glycerol: II. Salvage: Phosphatidate: I. de novo: 1) DHAP: 2) Glycerol: II. Salvage: Liver!7/11/15%4%Phosphatidate: I. de novo: 1) DHAP: 2) Glycerol: II. Salvage: Liver!Where have we seen this before? !7/11/15%5%Phosphatidate: I. de novo: 1) DHAP: reduction of DHAP, then acylation 2) Glycerol: phosphorylation,then acylation II. Salvage: phosphorylation of diacylglycerol In adipose tissue: Triacylglycerol catabolised To free fatty acids + glycerolGlycerol travels in blood to liverIn liver cells:Glycerol kinase produces glycerol 3-P200-600 times more activityHPhosphatidate: I. de novo: 1) DHAP: reduction of DHAP, then acylation 2) Glycerol: phosphorylation,then acylation II. Salvage: phosphorylation of diacylglycerol7/11/15%6%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 Triacylglycerol Synthesis Addition of a third activated fatty acid Phosphate Hydrolysis Acylation Enzyme: Triacylglycerol synthetase complex TAG made in liver, transported - To muscles: Energy production - To adipose tissue: Storage7/11/15%7%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 activation7/11/15%8%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. Tri-methylation of phosphatidylethanolamine Requires 3 S-adenosyl Methionine (SAM) SAM is a carrier of activated methyl groups Phosphatidylcholine Synthesis From Phosphatidyl Ethanolamine7/11/15%9%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 Fatty acid CoA Oxidation Reduction Fatty Acid added Activated Glucose: UDP-glucose Phospholipid Glycolipid7/11/15%10%Tay-Sachs!7/11/15%11%Surfactant Deficiency Disorder (Respiratory Distress Syndrome) Greater thermostability:• Branched hydrocarbon chain!• Ether linkage!• Many span the membrane!Archaeal lipid!Hydrophobic!Hydrophilic!Hydrophilic!7/11/15%12%This marks the end of Lecture 28…!have a great
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