PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Chapter 16The citric acid cycleCitric acid cycle also known as the tricarboxylic acid (TCA) cycle or the Krebs cycleYou will be tested on the entire chapterCatabolism of proteins, fats, & carbohydrates in the 3 stages of cellular respirationAfter GlycolysisGlucose + 2 ADP + 2 Pi + 2 NAD+2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O Glycolysis Cell needs to regenerate the NAD+ that was utilized in glycolysis NAD+ regeneration can be accomplished by aerobic or anaerobic metabolismWhat next ……Three possible fates of pyruvatePyruvateAnaerobic metabolismAcetaldehydeEthanolAlcoholic fermentationL-lactateLactate dehydrogenaseHomolactic fermentationAerobic MetabolismAcetyl CoATCA cycleElectron transportNADH + H+NAD+Alcohol dehydrogenaseNADH + H+NAD+Adapted from Chemistry 153A Course Compendium by M. A. BatesPyruvate dehydrogenase complexA cluster of 3 enzymes located in the - mitochondria of eukaryotic cells - cytosol of prokaryotesA classic well studied example of a multienzyme complexAerobic MetabolismNon-covalent stable aggregation of enzymesOverall reaction catalyzed by the pyruvate dehydrogenase complexOxidative decarboxylationIrreversible reactionRequires sequential action of - 3 different enzymes & 5 different coenzymesDifferent Coenzymes or Prosthetic Groups Required for Pyruvate Dehydrogenase Complex are1. Thiamine pyrophosphate (TPP)2. Flavin adenine dinucleotide (FAD)3. Coenzyme A (CoA)4. Nicotinamide adenine dinucleotide (NAD+)5. LipoateFour different vitamins required in human nutrition are vital components of this system Thiamine (in TPP) Riboflavin (in FAD) Niacin (in NAD) Pantothenate (in CoA)1. Thiamine pyrophosphate (TPP)2. Flavin adenine dinucleotide (FAD)3. Coenzyme A (CoA)Modified ADPCarboxylic group attached to -mercaptoethylamineHydroxyl group of pantothenic acid is joined to ADP moeityCritical to its role as an acyl carrier(vitamin B5)4. Nicotinamide adenine dinucleotide (NAD+)5. LipoateLipoate has 2 thiol groupsLipoyllysyl moiety is the prosthetic group of dihydrolipoyl transacetylase (E2)Pyruvate Dehydrogenase ComplexConsists of 3 distinct enzymes1) Pyruvate dehydrogenase (E1)2) Dihydrolipoyl transacetylase (E2)3) Dihydrolipoyl dehydrogenase (E3)Form non-covalent stable aggregation of enzymesEach present in multiple copiesThe # of copies of each enzyme & the actual size of the complex varies among organismsPyruvate Dehydrogenase Complex from E. coli E2 forms the core of the cluster to which other enzymes are attachedE224 copies Contains bound lipoateE1 24 copies Contains bound TPPE312 copies Contains bound FAD1) Pyruvate + TPP-E1 CO2 + Hydroxyethyl-TPP-E12) Hydroxyethyl-TPP-E1 + Lipoamide-E2 TPP-E1 + Acetyl-dihydrolipoamide-E23) Acetyl-dihydrolipoamide-E2 + CoA Acetyl-CoA + Dihydrolipoamide-E24) Dihydrolipoamide-E2 + FAD-E3 [cysS-Scys] Lipoamide-E2 + FADH2-E3-[cysS-cysS]5) FADH2-E3-[cysS-cysS] + NAD+ FAD-E3-S-S + NADH + H+Pyruvate + NAD+ + CoAAcetyl-CoA + NADH + H+ + CO2Overall ReactionReaction sequence of the pyruvate dehydrogenase complexEnzyme Reaction CatalyzedE1 Reaction 1 & 2E2 Reaction 3E3 Reaction 4 & 5Aerobic oxidation of glucose that includes the oxidation of pyruvate provides energy in the brain Thiamine (vitamin B1) deficiency- Unable to oxidize pyruvate normally- Beriberi, a disease that is characterized by loss of neural function is due to thiamine deficiencyHabitual consumption of large amounts of alcohol can lead to thiamine deficiencyBeriberi - is a disease caused by a deficiency of thiamine (vitamin B1) - that affects the muscles, heart, nerves, and digestive system- literally means "I can't, I can't" in Singhalese, which reflects the crippling effect it has on its victims- is common in parts of southeast Asia, where white rice is the main foodhttp://www.nlm.nih.gov/medlineplus/all_healthtopics.html#PReactions of the citric acid cycle466445Reactions of the citric acid cycleSteps 1, 3, & 4 irreversibleEnergy is conserved by electron transfer to FAD or NAD+, forming FADH2 or NADH + H+4 out of 8 steps are oxidationsAll of these reactions take place in mitochondriaCitric acid cyclePractice sheet # 1Citric acid cyclePractice sheet # 21) Formation of citrateCondensation of acetyl CoA with oxaloacetate12intermediateS-CoACitrate synthaseOpen form of enzymeClosed form with oxaloacetateOxaloacetateA stable analog of acetyl-CoA bound2) Formation of Isocitrate via cis-AconitateThe equilibrium mixture at pH 7.4 & 25 oC contains less than 10% isocitrateIn the cell the reaction is pulled to the right because isocitrate is consumed rapidly, lowering its steady state concentrationIron-sulfur center in aconitaseBasic residue(keeps the citrate in active site)1234SFeAconitase 4Fe-4S
View Full Document
Unlocking...