BICH 411 1st Edition Lecture 17Outline of Previous LectureI. Pentose Phosphate Pathway OverviewII. Oxidative PhaseIII. Non-oxidative phaseIV. Glycolysis and pentose phosphate pathway combinationsV. RegulationVI. Lipid ClassificationOutline of Current Lecture I. Fatty acid synthesisII. Citrate-malate-pyruvate shuttleIII. Malonyl-CoA formationIV. Acyl Carrier ProteinsV. Palmitate synthesisVI. ElongationVII. Fatty acid synthesis regulationCurrent LectureChapters 22, 23, and 24 on the next exam Fatty Acid synthesis-there are 4 big differences between fatty acid breakdown and synthesis-synthesis intermediates are linked to acyl carrier proteins (ACP) instead of CoASH-synthesis occurs in the cytosol-enzymes are just one Fatty acid synthase -NADPH is used for synthesis instead of NADH-2 carbons are added at a time (from acetyl CoA)-malonyl-CoA activates the acetate units – it’s decarboxylation drives the addition-these reactions repeat until it reaches palmitic acid (16:0), other enzymes can change palmiticacid to other lipidsCitrate-malate-pyruvate shuttle-helps bring acetyl-CoA into the cytosol from the mitochondrial matrixThese 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.-Fatty acyl carnitine can get fatty acid subunits into the matrix. In the matrix it can under go fattyacid oxidation to make acetyl CoA for the TCA cycle. Citrate is formed from the TCA cycle and is shuttled into the cytosol from that matrix, and is converted by ATP-citrate lyase to form acetyl-CoA and oxaloacetate. Oxaloacetate is reduced to malate by Malate dehydrogenase (which uses an NADH). Malate is then shuttle back into the mitochondrial matrix so there’s no net gain/loss in the matrix. The rest of the network serves to get the NADH and acetyl CoA to the cytoplasm. ***Good exam questions from figure 24.1: how do we make NADPH, how does malate get into the cytoplasm, etc**Malonyl-CoA formation-Malonyl-CoA comes from the ACC (acetyl-CoA carboxylase) enzyme-formation of Malonyl-CoA is irreversible-ACC requires bicarbonate (carried by biotin) and ATP (which drives the reaction forward)-one polypeptide-biotin (cofactor) carboxyl carrier protein-biotin carboxylase-carboxyltransferase**This is similar to pyruvate carboxylasereaction: Acetyl-CoA + ATP + HCO3-  Malonyl-CoA + ADP + Pi + H+-ACC is on when it’s a polymer, and off when it’s monomers-citrate favors the active form, palmitoyl-CoA favors the inactive formAcyl Carrier Proteins-they are very similar to Coenzyme A-ACPs are responsible for transporting intermediates -mammals use Fatty Acyl Synthase I (FAS I) while plants and bacteria use Fatty Acyl Synthase II (FAS II)-the synthesis is a cycle of six enzyme activities (all from just one enzyme: Fatty Acid Synthase)-The enzyme MAT starts the transfer of the acyl on acetyl-CoA to the ACP, as well as the malonyl group of malonyl-CoA to ACPPalmitate synthesis-Figure 24.7 shows the cycle of palmitate formation. ***Know the step 3 mechanism. It would be a good quiz or test question. -With each cycle, two carbons are added. Subsequent cycles start at step 2. Elongation-Prokaryotes don’t require oxygen for this, eukaryotes require oxygen!*It’s important to note that cis double bonds occur in nature, never trans double bonds!*Palmitate is the basis for all membrane lipids-the elongation of fatty acids is basically the reverse of the oxidationStep 1: Acyl-CoA  Beta-ketoacyl-CoA with thiolase.Step 2: Beta-ketoacyl-CoA + NADH + H+ L-beta-hydroxyacyl-CoA + NAD+ with L-beta-hydroxyacyl-CoA dehydrogenase. Step 3: L-beta-hydroxyacyl-CoA  alpha,beta-trans-enoyl-CoA + H2O with the enzymeEnoyl-CoA hydrataseStep 4: alpha,beta-trans-enoyl-CoA + NADPH + H+  Acyl CoA + NADPH. This results in an AcylCoA that is two carbons longer. To convert stearoyl-CoA to oleoyl-CoA, two electrons are passed through a chain of reactions. Two electrons are derived from the substrate. *Linoleic acid (omega 6 fatty acid) and linolenic acids (omega 3 fatty acids) can’t be produced in the body and thus must be consumed, deeming them “essential fatty acids.” Omega fatty acids are labeled based on how far a double bond is from the omega carbon.Fatty acid synthesis regulation-Malonyl-CoA inhibits beta-oxidation-Citrate, Insulin, and various hormones activate ACC-Fatty acyl-CoAs, glucagon, and other hormones inhibit ACC**Figure 24.16 is a good diagram of regulation – this would be a good quiz