BICH 411 1st Edition Lecture 18Outline of Previous LectureI. Fatty acid synthesisII. Citrate-malate-pyruvate shuttleIII. Malonyl-CoA formationIV. Acyl Carrier ProteinsV. Palmitate synthesisVI. ElongationVII. Fatty acid synthesis regulationOutline of Current Lecture I. Complex Lipid SynthesisII. Adding the head groupIII. Sphingolipid biosynthesisIV. EicosanoidsV. SteroidsVI. Lipid transport through the bodyVII. Membrane fusionCurrent LectureComplex lipid synthesis-Carbons on lipids are modified in a specific order: Fatty acid 1 is modified first, followed by the second fatty acid in the middle and then the phosphate head group third.**Cytidine triphosphate (CTP) drives the formation of CDP compounds-Phosphatidyl choline (PC) uses diacylglycerol (DAG) as the backbone and CDP-choline as the primed head group-Phosphatidyl ethanolamine (PE) uses DAG as the backbone and CDP-ethanolamine as the primed head group-other glycerophospholipids use a primed backbone (CDP-DAG)*Figure 24.19 shows how the glycerophospholipids are formed**the formation of CDP-diacylglycerol from phosphatidic acid releases a pyrophosphate (PP). These are spontaneously hydrolyzed with a Δ°G = -33.6 kJ/mole which provides the energy for the reaction.Adding the head groupThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-the head groups have an –OH group (alcohols) to which they are linked to the glycerol background-ethanolamine and choline are activated first with phosphate-these (PE and PC) are then activated with CTP which releases pyrophosphate forming CDP-ethanolamine and CDP-choline-for CDP-ethanolamine, 1,2-diacylglycerol phosphoethanolamine transferase adds it to thediacylglycerol backbone, releasing CMP in the process-for CDP-choline, 1,2-diacylglycerol phosphocholine transferase*triacylglycerols are made the same way except their headgroup is an acyl chain – formed primarily with acyltransferases-Phosphatidyl serine (PS) simply switches the ethanolamine group of PE with the serine group-Phosphatidyl Inositol (PI), phosphatidylglycerol (PG) and cardiolipin use CDP-diacylglycerol,(Primed backbone instead of headgroup)**PI is an important signaling molecule**-cardiolipin formation takes phosphatidylglycerol and adds another phosphor-diacylglycerol Sphingolipid biosynthesis-ceramide is the precursor for other sphingolipids and cerebrosides!!-Ganglioside GM2 has a sialic acid on it to which flu viruses bind***Eicosanoids-Eicosanoids (20 carbons) are local homones (basis of prostaglandins)-prostaglandin endoperoxide H synthase (PGHS) is a drug target! (aka COX)-prostaglandins mediate inflammationSteroids-cholesterol – most prevalent in animals (plants don’t have any)-in cell membranes, also a precursor to bile acids-synthesized in the liver – begins with the synthesis of mevalonate1st step: thiolase reaction2nd step: HMG-CoA formation3rd step: HMG-CoA reductase – target of cholesterol reducing drugs-cholesterol can have 2 carbons added with thiolase (unlike fatty acids) because the subsequent reactions have enough energy to drive the reaction ***good test question***3 mechanisms help regulate HMG-CoA reductase:-phosphorylation by cAMP-dependent protein kinases can inactivate the reductase-degradation of HMG-CoA reductase-gene expression (amount of mRNA)-Mevinolin converts to mevinolinic acid which acts as a transition state analog for HMG-CoA reductase-Lipitor does also!Lipid transport through the body -lipoproteins carry most lipids (HDL, LDL, VLDL, chylomicrons)-HDL (high-density lipid), LDL (low-density lipid - carries cholesterol), and VLDL form in liver cells-Chylomicrons form in the intestines-lipoprotein lipases hydrolyze triglycerides from lipoproteins**You want High HDLS and Low LDLs**Brown and Goldstein proposed the Hydrophobic handof modelMembrane fusion-requires proteins to pull the membranes together-virus binds to sialic acid on membrane, then the cell takes the virus in with endocytosis-all membrane fusion reactions so far use the helical hairpin structure-hemifusion – need point-like protrusion in one or more membrane to get them close enough to spontaneously mix and then be breached-Ebola is not transmitted through the air!! It’s in the blood cells. Flu however can be transmittedthrough the air.-Flu infects the lung epithelia, while Ebola infects endothelial cells like blood cells and liver cells.-most likely the Dallas nurses got sick while taking OFF the protective gear that was