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by: Sylvester Mante


Marketplace > Texas A&M University > Biochemistry > BICH 303 > ELEMENTS OF BIOL CHEM
Sylvester Mante
Texas A&M
GPA 3.64

Timothy Devarenne

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Timothy Devarenne
Class Notes
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This 29 page Class Notes was uploaded by Sylvester Mante on Wednesday October 21, 2015. The Class Notes belongs to BICH 303 at Texas A&M University taught by Timothy Devarenne in Fall. Since its upload, it has received 53 views. For similar materials see /class/225849/bich-303-texas-a-m-university in Biochemistry at Texas A&M University.




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Date Created: 10/21/15
Citric Acid Cycle was mum Thammn What is the fate of pyruvate Depends on the 02 conditions of the cell Aerobic conditions pyruvate enters citric acid cycle TCA cycle reduced to CO2 to generate reducing agents for ATP production next lecture series rithaerobic conditions I Anaerobc glycolyss the production of lactate from pyruvate Occurs in muscles 2 Alcohol fermentation production of ethanol from pyruvate Citric Acid Cycle Krebs cycle TCA cycle cycle intermediates have 3 carboxylic groups Amphibolic plays roles in Metabolic intermediates of TCA cycle can be used for anabolism In terms of energy production TCA cycle produces reducing agents NADHFADH2 for use in ATP production we will study each reaction in detail you must know each enzyme name amp order structure of each metabolite oznns mokycaie mumson Citric Acid Cycle Sir Hans Adolf Krebs 1900 1981 German born biochemist In 1933 he was barred from carrying out science in Germany because he was Jewish emigrated to England and became scientist at Cambridge in 1937 published paper in Biochemistry Journal describing citric acid cycle Nobel Prize in Physiology 1953 Citric Acid Cycle Glucose not only input of pyruvate for TCA cycle All provide e39 for Catabolism can be broken down into 3 stages TCA Cycle is central to catabolism and anabolism Stage 1 Slage 2 Slzge 3 Amymm AmLylCoA Electron may pmducliml I ynmuc oxidalion and nxida ve dchydi39ogcnase phosphurylnliall Rtspi mry rompie coE Rf Glucose 9 nmvm r a c7 1 ll Amino 74 m ids r talcumquot i mnsrcr mainw ADP ADH reduced 0 cum ersi 2 17 hing 1120 ems ankslcalz l39homsnn Citric Acid Cycle Cellular Compartmentalization of glucose oxidation f J jf J Sage 1 Saga 2 Stage 3 Acelyl Acetyl CoA 2122mm imam praduclinn PYanuI oxidnliun and oxida ve lollydmgenuse thphnryh on cumplo co mgmxgg niurose memo r s Fany acids Amino 7 Q and H nu2n 1120 ms Elaakglcnlg Thurman Citric Acid Cycle Mitochondria Double membrane system outer membrane inner membrane creates structure matrix region lulu 39 Inner mmihrmm membrane 1ituulmultquot39 kudopi39 niL iuiium y Muu ix Omar memhmnc Ii Esme Imm uu r z mcmhmnr mt mhmnr 0 1 ll 7 llH llljleIhuh O H t L l39 11 Pynnuc u ANN hmuu a hydrnp nicr um w 7 quot Citric Acid Cycle Steps before TCA cycle IlA u 3 mm 4 1mm an t Lu l li Arnyll39nA l u a l x nun Ml LHer quotlulu I 4d LL 39UU39 r39 0 ulunmulv TB Ht l 539 quot739 ffAx w 391 H j xm qu u llU Z LOU llt UK m M l 39 I I II IJII39 hulLuAu A o If 0 HIV quotin u inn 7 lll39 um I TRICARBOXYIJC ACID 39 39 L CYCLE m 39x39r um 11 citric acid cycle H Fumuur Krehn rydt39 L U rquot W TCA cycle on mm I o I II I dnhvur mm V I 1 N um u 139 mm 11 um39 kw H K V mutualman it 10quot Sw r uuw I l LL IV V mm au sut quotm mlmmphm n lull1 5mian 1E7 2006 BrooksiCole Tncmson lilti u ur nxr quot4 1 4 hr 4 1 N mglularur 1 pyruvate is transported into mitochondria 2 pyruvate dehydrogenase removes acetate bound NAD is reduced to NADH 2 carbons remaining from carbon pyruvate derived from 6 carbon glucose 3 Pvnwate O GOASH de hydrogenase CO 2 O H complex l I CPL I COO quot IHg J S COA 39 Pymvale NAD NAD H H macs swamp Hmmsnn Purpose of CoA AcclyllnA imwglm I1 b Citric Acid Cycle Step 1 formation of Citrate mmquot a mmnnm 39 The condensation or acetylCoA and oxaloacetale m n v quot x 0 t ormcirrane Overall reaction n O 100 i i 17200 0 H2 MthlCu l Ciume svmhase CH2 time 5 imng H30 39 H07 7700quot Ion eSH 5 i m I Muir A Iii tlkr k hum LH AH IX u 39 quot ZHZ lahtr I 39 n I Unnloacaime lirh lngvnnu u mr LOO r o39 mailmann 5 IN I A 4 i m 39x 17H at It 2mm 111 0039 ma mnksrCnie mnmn reaction carried out by the enzyme lr J Um HH ZUXF H39V 39AU u Mame GUM mutant 0 acetate from acetyICoA is combined I TRICARROXWJC ACID Iquot oxaloacetate V t vcuz ML H citric acid Qldf IKE U Funuuu Krebs cycle IHI t x I I I rumcm energy Input not reqwred due to thlol 8 bond between CoA and acetate n ntzmz Sw tmur citrate has H 397 H39 E Styli 11quot r 4nH39 y 39 W l W 1 r39 H 1110quot 11 41 m39 v 1 I n l V quot2 l I ang IuiM uI r nn Dull lming M LupinIgnaz U l muman K man Suninme LE 2006 Brooksi Cole Thomson Citric Acid Cycle 1 Pymmc i la y n Step 2 isomerization of Citrate to isocitrate w I GHQ COO CH2COO I l Aconitase HC COO HOi C COO l l 1362 HO CH CH2COO l COO n 1c 1 39 um Amyium 1 than V 7 1 xx 1 m i V dulnw NIL in Citrate Isocitrate quot quot n in 139 m 7 H I I m UT IMF museum um I l H z um39 Ir no z uxr 39 39 H i 39 i reaction carried out by the enzyme JV lig Uu 391 Omn lwmu ul 07397 o hvmiur I reqUI res Fe II TUUV 1 nucnaoxnjc ACID W cm quot NCIJ39Z m ux um I citric acid 710 V Krebs ryd 1 ml39 u N mm OH moved to C 3 of iSOCitrate ux llll 39 lintquot ILA 00 xum Immorx mu quot3C 20039 Suihum Hrnun Mlii u39 quot m quot m l If 11 ll l TOn IKV I 2 7 e 1 1 Kcmg1marur A n 39 up u uw A i 439 mix343 ndm n m pinup a x J m SunMM 2006 BrooksiCoie A Thomson Imlthn Citric Acid Cycle Step 3 x ketoglutarate formation quotIIu minmgr mm w H C C00 11 I 7 Il39 hn OH kuyK nA a K quotlr 39 L wMNlI39 39LH A luau l I chrzue quotmuquotgquot Us H m r o klmlrngmase l39 9 munmm ml quotxi m 1 oxndatlon HWLIB uxr m mn u39 nn T uxr LC IXF 39 V xv W y 2 decarboxylatlon mm mnr Hz 00 WM 9 W O H r COO 55 H c ltK j 2 l 039 A nr nn39 H 5quot 41 K K n mmnnnxmc ACID x f x M39Ui m xr 0 X39 0 COO m39 K Oxnlosuccinme aKemglnmmte T cydc 1 eznnsamsscsznmmnn 1 IMMUNI o reaction carried out by the enzyme Inc xr we 4 H P L xh nnlnqnmu tut um umlwun in Kr re 397 NAD is reduced to NADH l 391 n r ax h hln quot hm may unwmm w 1I Hams lt o 0 thuluqnml snmmwm one remaining C from pyruvate i 2005 BrooksJCole r Tnomson i Citric Acid Cycle Step 4 succinyICoA formation l n uuu 4 livmnrnuv mm n 100 Torr ltH In2 422 1HZ 39u I H 11712 NAD zoA SH CH2 NADH H C02 nkl39tyLCAvk I I A I i 1 0 10 v Mm mm I 1 uxr gt4 W iy 39 quot UIl l1il j 00 5 A o W o R quot me u mgiummm SuccinyHlm U a 1 rtm 1H II n r xx i rru um I I reaction carried out by the enzyme hhn Bum hmunu I o i 4 o ocketoglutarate OXIdatlon to reduce it TRICARBOXYUC 3 yam 1quot lt39lLricacidry39 c Fumxlnr 39 5 carbon ocketoglutarate to innmain H m a 4 carbon succmyl LC 710 um i u39 in quot 51 me third no remaining C from pyruvate Sun39nulr ilil ll l ll39 l 1 1 ll I it 39Algt li mmmmarl39 ng 1m Hg l L VKL 4 n u rmvH39iuA IE 2006 Brooksi39Cole Thomson i Citric Acid Cycle Hanqlnvluu 1m r quot39 L Step 5 succinate formation IE quotn n foo 1H 3 Succinyl C CO 7 CoAsynLhetase I gt CH2 GTP l COA SH l l l 70 1H l s 00 Mg I u MenH nA 1 ix gt nu TV I u 4 tl xi rnn Succinale F39ll39nll39t llll ll1I x 1 II 62005 mum l39nomsnn Hm39 lm 31m 4 nu l uxr ULW reaction carried out by the enzyme hum 39L o 39Analr xv P and energy from succinylCoA TIUCAR BOXYUC ACID CYCLE breakage is used to form GTP citric acid qrdc I r r x 1 hrth cycle hnmrm TCA Cycle UH P is by J nucleotidediphosphate kinase m n 039 llgL K gtIu i ru i V HgIL nn I substrate level phosphorylation cnn39 y Mic run 3 v 0 a quot vVwmmulinlr z sun v hun ltlurlu 0 luimlw ony In cycle mummyA it 2006 Brookleole Thomson Mireillequot Citric Acid Cycle Step 6 fumarate formation xmi wquot l airu Succinate FumarnIe c run r SwuksiCuier mmun IIU Livux F ll l lnu reaction carried out by the enzyme enzyme bound to mitochondrial iX 39 39 FAD acts as e acceptor instead 114 F of NAD ii39 UgtU39 bond between c 2 amp 3 is oxidized to double bond 1552006 BrooksiCole Thomson humglxuhxu F ll l 5 Citric Acid Cycle Step 7 Malate formation 000 H 39n Vu21 Pmmu hungnuquot c H coo w quot I V Ii 1N o I v39 0 hllxummie Fumarate Mn 1 K 1 in I 3 gt 00 H i mauasmisimermmn il i ux 1m u lil 1 39x JR 2A U COO c H20 gt HO C H reaction carried out by the enzyme 0 Austinquot double bond of fumarate is H TRICARBOXYIJC ACID I K 39 CYCLE Ii 00 H O 1sz citric acid cydc I 2 lunuut h r Thu Milt t Ir Inmx39 TCA cydc nu Sm39nnlr drhvdrozreulr 7 H m mumm ll LIZ UU39 mi 4 H lakhwlnxulmr ilxi 39x r surmnm uu m JAK ll u u E Il ux39 millll H 3 I V x M l a lull quot n c 11039 u uxr i y K quotII V l a umxnguiarm 7 U m i Knu lminle Aim at quot2 1 I dvhnlnqrxuar mptuupnm u In Sur nyIkm 512006 BrooksiCoie Thomson i Citric Acid Cycle Irrrmqinrinug inn z Zf Step 8 Oxaloacetate regeneration COO COO i gt o NADH PF CH4 CH2 0 i l 1 Au quot 100 coo HO C H NAD39 hl 1w th lnmug nn lLl LNI n r 0 L Malate Oxaloacetate Iquot o mulourmw no 39 39 Il ZZDOquot ll ttnl Il 39 reaction carried out by the enzyme mm Jlmlr I mmin mun tie a 0 li nn TTUCARBOXYIJCACH AliJur O39ClJZ HL er i x M n citric acid cycle I Fumxmr Km q dr39 m1 u zJHHHJ TCA cycle nu ELM W x mm Igli KKF m H P unmixfi Mir omn quot t 4quot I w H 111 i u lip HM quot xiir M 39 I 1 i oxaloacetate can now react With nit 7 another acetyICoA SualmK39AA I i 2005 Brooks Coie Thomson F Citric Acid Cycle r Reducing agents formed 1 pyruvate to acetyICoA 1 step 3 isocitrate to aketoglutarate 1 step 4 ocketoglutarate to succinyICoA 1 step 8 malate to oxaloacetate step 6 succinate to fumarate 1 pyruvate to acetyICoA 1 step 3 isocitrate to ocketoglutarate 1 step 4 aketoglutarate to succinyICoA Af39ter ocketoglutarate cycle continues to reform oxaloacetate mans EmaksiEuig mmsnn Citric Acid Cycle Eventual ATP Production 4 NADH for each NADH Miami 1 FADH2 WW 1 GTP Total from one pyruvate Total from one glucose Next lecture series Will deal with how reducing w agents can be used to produce ATP mm l M W ruin 7 o quotLN 0V l uuuuuuuu m mans Emakleulg l39mmsnn Pvt 39u39 inhibith 39 ATP x maul10A and NADII tei l lu lnllibilwi ln ATP NADI I 39 39 39u z Ie sli xuioncrnuc T X t Zimm 1 Cl l u it lwciimic j 5 Maia lo Fumurale Citric Acid Cycle Control of the TCA cycle Pyruvate dehydrogenase Inhibited by When these are abundant X Control points Inhibition ofi uaction Step requiring iectrun acceptor either NAD1L Inhibil i In39 A39l39li NADU Stimulatel 39DI NAN mlixluglu iztrutu 5 succ im39l in ms amawcme r Mormon Stupinuli Iltllillilt X RSWIHW M ATI NAD i uml I by MA energy production is not needed activated by Citric Acid Cycle Control of the TCA cycle Citrate Synthase produces citrate Allosterically inhibited by many compounds I X xuloucmuc A 2mm PH m39uu39 l gt gt x TELEYIZJAIASNADII tei l 39u 39 lnIIiIJilwi ln TI NADII I WM 39 mme X Comm points Inhibition ofruaction Step requiring iechun acceptor either N L When these are abundant energy production is not needed iwcitmic 3 Main lo J Inhibin In A39l39li NADH Slimniuiexl mum NAN 1quotng we wiiclugl u izirulu Surrinalr y x itijitcgti 39 succln39l MA in ms amawcme r Mormon Citric Acid Cycle Control of the TCA cycle Isocitrate Dehydrogenase produces ocketoglutarate allosterically inhibited by I X xuloucmmc A 2mm 3 Mululo lwtimuc J Inhibin In39 A39l39li NADH Slimniuiexl n39DI NAN wliclugluizumu When these are abundant Fumarale 13 Slltpill lll x 34 39quotNli I s uccim39lIIIA energy production IS needed in ms amawcoie 7 mm PW 39u39 inhibited by AT 1 x 39IL elVlTnAzlml NADH cei l 39u lnllibilwl In TT NADII H 39 my X Control paints Inhibition ofruaction Steprequiringciecuwn acceptor either Nr L Allostencally stimulated by Citric Acid Cycle Control of the TCA cycle ocKetoglutarate Dehydrogenase produces succinyICoA allosterically inhibited by I X xuloucmuc A mm PH m39uu39 l gt gt x TELEYIZJAIASNADII tei l 39u 39 lnIIiIJilwi ln TI NADII I WM 39 mme X Comm points Inhibition ofruaction Step requiring iechun acceptor either N L When these are abundant energy production is needed iwcitmic 3 Main lo J Inhibin In A39l39li NADH Slimniuiexl n39DI NAN 1quotng we wiiclugl u izirulu Surrinulr y x itijitcgti 39 succln39l MA in ms amawcme r Mormon Citric Acid Cycle Control of the TCA cycle Relationship between energy requirements and enzyme activity ATP NADH x inhibited l39 ATP ADP NAD I X xuloucmmc A 3mm 39IL eU lTHA and NADH tei l 39u 39 lnllibilwl 1 TT NADII I WM 39 mme X Inuiml points Inhibition ofruaction Step requiring iechun acceptor either N L Enzyme actIVIty iwcitmic 3 Mululo Inhibin InA39l39l NADH Slimniuiexl n39DI NAN ATP NADH ADP NAD Fumarale we wiiclugluizumu Surrinulr y Inllihilml hv x tfN3isw39 Enzyme activity was amawcme 7 quotNorman Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism Catabolism Wit Inputs to TCA cycle from many sources smnc gnome and 41 mo Curbulmlmlm TIII39L OIIinL nlvminr 1w h and h39iit39mc P i lemlyxi L mmc tum u39yptnplhm cotkas 1mm mitochondrial mcmhmnu v L Mimchondrinn 133 f may gt mva i ixnx l yx39llullc J Asp Asparagmc in l k llmu39ltuc i Fquot Immut t Tyrosinu qu phrnyhiluninu Lyn m1 meiuuuu quot I TTA 39 I ltiiumm T Suu manA i i f Th canine All nll Ol k39i l and mulnnninc 39ninu V A quotI histirlmr mans Bwoksicaie r mnman Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism Anabolism luhnlwtliuiws39 1mm initulhnulllidl Mitochondiion m up PEP and malate can be transported to cytoplasm mum m39ugcncxii I 391 1 ii xu li mccm Us Mainly I Oxnloacciutc lm i Mnlzuc soc Tm n J hmmmlu mm 7 3mm Succmyl r 9 ems BNDNGM Thurman Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism Anabolism lt4 i 1 Citrate can transported NADI H gt Imur miunlmmlriul ikliimimmliinn MW converted i i F393 lm 2 txxccinuu xuluacuuuc J I A E Iu39inylCUA zinmt I elogiu izuuxe gt lmcium 39 Ill39 made into lecture 17 Fully mm NAI uu H MIA DH Accn 1 In quot 1 204511 gtxiwvmm J m Alt 1 Am ATP a i o zaps anksicaie Thnmsim Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism Anabolism I39JLKT39 T Many of the TCA cycle mix intermediates can be used m3 xd39 LjCluc mum and bunmm ladmhnlmtc K i mdxlmullk lrl ulilw PEP T In 4 1 71 mum Phl39lhldh Iryplup 0AA mm Uxulunmmlc Aipnruue I Mat Axpmrmw qu muu mm onlummu Suctllmllt SuunuvICof T u ant Mimmomman Ilmm Imml mlluclmullnnl mm I mpimins mas BlacksEat mmquot Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism Obviously TCA cycle is a central player in both catabolism and anabolism P L m MU Ion During anabolism TCA intermediates Need to be Otherwise cycle shuts down V XdltmLL l AlU Iiliuw F 9 Anaplerotic reaction reaction that Muluu quot32 WW E mum u r1 magi unm S39miWW S m39h 39l 3 Transumiuzitjon I lliilillnini mans Emaksicnh rThnmsan Citric Acid Cycle Citric Acid Cycle s role in CatabolismAnabolism TCA cycle is mainly replenished with I yt m Ju 0 Main anaplerotic rxn carboxylation of Carried out by pyruvate carboxylase 4 High levels of acetylCoA activates pyruvate carboxylase Oxulmwuuu lit at V Iilril Add Inmnm Muluu db W 1 I V I plunm u r1 elxmugluiul39uu Sun in39mr Snu im39l iu Tmnsumiuzltiun I I lluuunau mnus Emaksicnh rThnmsan Citric Acid Cycle say 1 Stage 3 AuralCM AmlylCOA ElecImn mim p naduclion Pytmxm oxidalion and axida ve dehydrogenase phosphuryla on 2 V V r complex co lucose l ynwmc 39 1 a Fauy 15 9 acids Amino acids mans Emaksmai mmn


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