MCB102-4 - MCB102 Fall 2008 Regulation of glycolysis and...

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Unformatted text preview: MCB102 Fall 2008 Regulation of glycolysis and gluconeogenesis Reading: pages 423—430; 582 (Section 15.3)-590 Outline 1. ATP, ADP and AMP regulate enzymes of carbohydrate metabolism allosterically. 2. The concentration of AMP is more important than the concentration of ADP in sensing the starved state, because adenylate kinase converts two ADP to one AMP and one ATP. _ 8. Hexokinase in liver and muscle have different Km’s for glucose, so that liver can feed glucose to muscle. Phosphofructokinase-l is regulated allosterically and hormonally. Glycolysis in muscle is controlled somewhat differently that glycolysis in liver, because liver performs gluconeogenesis. 9"?“ Scope of the lecture Humans eat at least a ton of food each year and maintain approximately the same weight. This arrangement requires quite complex controls, some of which will be covered in this lecture. Part of Chapter 15 covers the regulation of carbohydrate metabolism at the levels of hormone - cascades and allosteric regulation of enzyme activities and Kms of enzymes. In order to understand this material, one needs to read part of Chapter 12 (Bio—signaling), as indicated in the reading assignment above. The hormone cascades covered in this course are those that involve the hormones epinephrine and glucagon, which regulate a protein kinase called protein kinase (protein kinase A). ATP and AMP are common allosteric regulators in carbohydrate metabolism. Your textbook describes an enzyme called adenylate kinase. This enzyme converts two molecules of ADP to one molecule of ATP and one molecule of AMP. Adenylate kinase 2 ADP (-9 AMP + ATP When ATP is used up, and the cell needs more, ADP can supply some ATP from this reaction. The authors of your textbook believe that the concentration of AMP in the cell is a better sensor of the need for more ATP than is the concentration of ADP. due to the adenylate kinase reaction. AMP is seen more frequently than ADP as a positive allosteric regulator of enzymes that help generate ATP. ATP is a negative allosteric regulator of enzymes that help generate ATP. Different hexokinases have different Km’s for glucose The enzyme molecules that convert glucose to glucose 6-phosphate are not all the same. Different polypeptide chains, called isozymes, can catalyze this reaction. In muscle one calls the enzyme hexokinase because it phosphorylates more than one hexose: glucose and fructose are phosphorylated. In liver one calls the enzyme glucokinase, because it only phosphorylates glucose. Hexokinase in muscle has a Km for glucose of 0.1 mM. It is very greedy and converts glucose to glucose 6-phosphate for glycolysis, even at low concentrations of glucose. In contrast, glucokinase in liver has a Km for glucose of 10 mM. It is not selfish. It is altruistic. One of the liver’s jobs is to supply glucose to the muscles in times of glucose limitation. 1.0L Hexokinase I Hexokinase IV (glucokinase) Relative enzyme activity .J x i v i 0 5 10 15 2O Glucose concentration {mm IffiflRE 1542 Comparison of the kinetic properties of hexokinase IV (glucokinaae) and hexokinase L Note the sigmmdicizv for hexokinase IV and the mesh k‘awer Km for hexskinasc 5. When bison glucose é‘éses genre 5 mm, hexekinase EV activity Encreases, but hexotinsse l is at ready operaténg near yam and cannot respond m an merease in gin-r H case CGE'ECEFI’WMEDFE. Hexokinases l, H, and :n have similar kinetic properties. Page 1 Phosphofructokinase-l is subject to allosteric and hormonal regulation. Glycolysis is regulated, so that it is used only when needed, that is, when the need for more ATP is apparent. Pathways are supposed to be regulated at the first committed step, so that the cell does not waste energy making useless intermediates. Thus we must seek the first committed step of glycolysis. The hexokinase reaction releases -16.7 kJ/mol, so one might think that this is the first committed step of the pathway. However, the hexokinase reaction is also part of the pathway of synthesis of glycogen, which is a storage form of glucose made in skeletal muscle and liver. Moreover, the hexokinase reaction is part of the pentose phosphate pathway. In addition, glucose 6-phosphate can be hydrolyzed by glucose 6-phosphatase and released to the blood stream in liver. Therefore, the hexokinase reaction is not a good reaction for regulation of glycolysis. PENTOSE - mospmm“ GLECOSE 4 P "’ “WOW LP a: UDP GLacoSE—wLYCoHN ’PHTHWAY GLYCOLYSLS Looking further down the glycolysis pathway we see phosphohexose isomerase, which takes up energy (+1.7 kJ/mol=G’o) and may not therefore be the best reaction to be a committed step. However, the phosphofructokinase-l reaction releases -14.2 kJ/mol and is arguably the first committed step of glycolysis. GL uCoSE + fl: G ucoSE mgr: “Zolé'tl’mwmsg m :0 0m 5 M - "Mme- “60851-46 05 GLuwSE fATF‘r—A AW" GLMOSE é P PHOSPHO' ?HoSPHo- GLMCo MWfflSé H E14056 momma“ FfiucTcSE 6' P W‘ rFK—l A32? FRMT‘OSE 1,6 BIS-P Enzyme inhibition is supposed to be caused by the end product of the pathway, which is in this case ATP. In fact, ATP binds to an allosteric site on phosphofuctokinase-l, inhibiting the binding of substrate. Moreover, AMP and ADP bind to an allosteric site in PFK-l, stimulating the binding of substrate. A No Enhibitors (low IATPD a \ .Z 6 / {I} 8 g 1 mM ATP % + 0.1 mM AMP 8 3 “5 E D. m 9 a . L i L .L O 1.0 2.0 [Fructoseephosphate] mM FIGURE 17-33 PFK activity versus F6P concentration. The various conditions are: blue, no inhibitors (low, noninhibitory [ATPD; green, 1 mM ATP (inhibitory); and red, 1 mM ATP + 0.1 mM AMP. [After data from Mansour, TE. and Ahlfors, Jl Biol. Chem. 243, 25234533 (1968).] Control of PFK-l stops glucose and galactose from entering glycolysis when they are not needed, but entry of three—carbon compounds also needs to be controlled. For example, glycerol goes to glycerol 3-phosphate and then to DHAP and to GAP, so glycerol circumvents the PFK—l reaction. Entry of glycereol into glycolysis is stopped by allosteric regulation of pyruvate kinase. ATP inhibits all isozymes of pyruvate kinase in all tissues. Control of glycolysis and gluconeogenesis in liver Glycolysis and gluconeogenesis are under reciprocal hormonal control in the liver. When the concentration of blood glucose becomes low, the pancreas secretes a 29 amino acid peptide hormone called glucagon, whose amino acid sequence is shown below. HSEGTFTSDYSKYLDSRRAQDFVQWLMNT This hormone binds to a membrane receptor in liver. Upon binding glucagon,, this receptor changes shape. In its new conformation, the receptor causes an allosteric change in a membrane-bound “Gs protein,” which contains three subunits and is bound to GDP (s stands for stimulatory). Upon contact with the glucagon-bound receptor, the G protein releases its bound GDP and binds GTP instead. When bound to GTP, the G protein is activated to release it’s or subunit, which is bound to GTP. The GTP bound to the G protein’s or subunit will soon be hydrolyzed spontaneously to GDP and phosphate, so the effect of Per 4 the G protein a subunit on adenylyl cyclase is short lived. The G protein’s oz subunit, bound to GTP, stimulates the membrane—bound enzyme, adenylyl cyclase t0 synthesize 3’-5’ cyclic AMP (CAMP). The CAMP made by adenylyl cyclase will in turn bind to the inactive form of protein kinase A. This binding of CAMP causes the regulatory subunits of protein kinase A to dissociate from the catalytic subunits, which then become active. GT?) Seancsirm itiphofiphq’ie P“? 5 :3; ‘; TKRNSDVLCTION OF THE GLUCAG—OM SDGNAL ACIYCLIC \/ MC L EoTibE 7H OSPHw H O HO; puck XLATION ’DIESFEKRSE a; aTHE K SzAmo rgoTEINS ® C2) ® G5 with GDP Contact of G3 with G3 with GTP bound bound is turned hormoneqeceptor dissociates into a off; it cannot complex causes dis- and [3‘7 subunits. activate adenylyl placement of bound Gag-GTP is turned cyclase. GDP by GTP. on; it can activate GTP adenylyl cyclase. GT? bound to Gm is hydrolyzed by the protein’s intrinsic G'l‘Pase; Gm thereby turns itself off The inactive ex subunit reassociates with the 87 subunit. FIGURE 12*5 Self—inactivation of 65. The steps are farmer described in the text. The proéeén's mfrénsic G?Pasc amt-{:32 in many rages stimu— lated by pieieén: {regulators cf Gsmteén gignaiing}, deiermisaes hew quédfijv beans 6?? bydrcaiyzezf a) CD? and 2%qu new Eong she G prcuem remains active. Adenosine 3’,5’—cyclic ‘ monophosphate (CAMP) Cyclic AMP g cyctlc. NacLEoTIDf ’PHGSPHODIEJTEKHSE 3/” 2 Adenosine 5’~monophosphate (AMP) AKA? \. Dimerization Substrate- 1' domain binding cleft / Inhibitor Catalytic Sequence subunit: Regulator r ’/ subunit 4 CAMP Substrate—binding cleft now available \‘2 CAMP FIGURE 12—6 Activation of CAMP—dependent protein kinase (PKA). (a) When [CAMP] is low, the two identical regulatory subunits (R; red) associate with the two identical catalytic subunits (C; blue}. in this RHCZ complex, the inhibitor sequences of the R subunits lie in the substrate— binding Cleft of the C subunits and prevent binding of protein substrates; the complex is therefore (‘atalvtically inactive. ’ihe aminoterininal Sequenu-‘s of the R subunits interact to form an R} dimer, the site albind— ing to an A kinasr‘ anchoring protein (AKAP; green), described later in the text When {(AMPI rises in response to a hormonal signal, each R suhunil hinds two (AMP molecules and undergoes a dramatic rcnrgaw ization that pulls its inhibitory Sequence away from the C subilnilrope ing up the substratcibincling Cleft and releasing each C subunit in its (k alytically active iOFITL Protein kinase A uses ATP to phosphorylate and inactivate liver phosphofructokinase-2 (PFK-2). The phosphofructokinase of glycolysis is called PFK-l. PFK-2 uses fructose 6-phosphate to make fructose 2,6 bisphosphate. 6 0 l? . ‘ ll - CHZOPOB 1 PFKi 3L “O—P~O—CH2 0—-P—0 /0 CHZOH l O l, ‘ D? + 0‘ 0 5H H H0 5H 4 ATP ~——-/7 A H H0 4 s H CH20H OH H OH H Fructose 6-phosphate Fructose 2’6_bisphosphate Fructose 2,6 bisphosphate activates PFK-l and glycolysis. Thus liver glycolysis is not stimulated in response to the glucagon hormone cascade. Instead, this hormone cascade turns off PFK-l and glycolysis. Moreover, liver PFK-2 contains a fructose 2,6 bisphosphatase activity (FBPase—Z) that hydrolyzes fructose 2,6 bisphosphate to phosphate and fructose 6~phosphate. This fructose 2,6 bisphosphatase activity is stimulated by the phosphorylation catalyzed by protein kinase A. This activation of fructose 2,6 bisphosphatase by the hormone cascade is slowly reversed by enzymatic hydrolysis, catalyzed by an enzyme called pho‘sphoprotein phosphatase. \ \ l l / / / \ Fw—fi-fl \ / PFK~2 /_ ereBP] :/ (active) /\OH 3' Stimulates gly‘tiol‘ySis, FBPase-Z V inhibits gluconeogenesis 7x (inactive) ‘\ 1, m " ' \ I \ l l x Fructose 6- hos hate P‘ l l /'A’1P ATP P p ‘\ P, “\H,‘ ,- \ PM) 1" AMP-1': » l» t Hype} q ' lplmmn Ll upem (.11 @ (____~ glucagon ‘7 'Slfi-u - »» , l_-. i m” r _ ADP //\pluospl1atase plum“! [mm C ;\ VT [CAMPD , . / l ,i Fructose 2,6-bispliospliatej5; H20 ’ l i A ADP ¢ \ S - (a) PFK—2 l o WFQGBP -(' active) ii I V ‘ ~ ---- ” ,2 O‘PVO‘ Inhibits glycclysis, 9‘ wBPase—2g‘ ’ l stimulates gluccneogenesis — (active) 4,! : 0' / 1 g \ 1 I l l l (b) “CURE 1547 Regulation of fructose 2,6—bispbosphate level. {a} The {WK—2f: and its breakdown by fructose 2,(ebésphosphatase lFEPaseEE. craélrzla; zicncemrstioo of the reguéa‘v‘r fructose 2,6—E’éésphcsphate {F2689} (b) Both enzyme aciivltées are part of the sa polypeptide chain, and i5 deferméned by the rates of its syoébesés by chassis-heirscickénasez they are reciprocally regulated by insulin and glucagon m2 7 Liver gluconeogenesis is inhibited by fructose 2,6-bisphosphate, because fructose 2,6-bisphosphate binds to an allosteric site on fructose 1,6- bisphosphatase-l and decreases this enzyme’s affinity for fructose 1,6- bisphosphate. Thus fructose 2,6—bisphosphate has opposite effects on PFK-l and FBPase-l. The net result of the glucagon hormone cascade is the stimulation of gluconeogenesis and the inhibition of glycolysis. This allows the liver to make glucose, which can be exported to the muscles when the blood concentration of glucose is low. 100.rw A: #4 O Q 3 Got 5‘ __.__ _______________ we IE 3 4o: , a . H l E i I F34 I l _ a ,,,, .. l 0.05 0.1 0.2 0.4 0.7 1.0 2.0 4.0 i i l ZOi oi [Fructose 6-phosphatel (mM) (a) A 100 — g i i 80 ~ 0 5° >> 60 - r; __ ______________ s_ *5 m 40 H % 20 “ +F26BP Eu 0 l L- ,,, 0 50 100 [Fructose 1,6-bisphosphatel (,LLM} (b) Gluconeogenesis T ATP / Fructose 6—phosphate 6\ Pi PFK-l @e—~~~ F26BP ~~~~a® FBPase-l /\ ADP Fructose 1,6-bisphosphate / H20 FiGURE 15—16 Role of fructose 2,6-bisphosphate in regulation of gly- colysis and gluconeogenesis. Fructose 2,6—bisphosphate (F26BP) has Opposite effects on the enzymatic activities of phosphofructokinase-I {PFK—l, a glycolytic enzyme} and fructose 1,6»bisphosphatase (FBPase— 1, a gluconeogenic enzyme). (a) PFK—l activity in the absence of F365? {blue curve) is haif»maximsi when the concentration of fructose E-Qiiosphate is 2 mm {that is}, KM 2 3 mm}. W'iicn 0.73 um F268P is Present {red curve), the for fructose 6—phcsphate is oniu 0.08 mM. 7 Peri? l Glycolysis («2) Thus F268P activates PFKJ by increasing its apparent affinity for fruc- tose 6-phosphate (see Fig. lS—Mb‘i (b) FBPase—i activity is inhibited by as little asl ,LLM FZGBP and is strongly inhibited by 25 ,(LM. in the ab- sence of this inhibitor (blue curve) the K05 for fructose 1,6-bisphos— plate is 5 MM, but in the presence. of25 lbw. F2éBP {red curve} the K95 is >70 um. Fructose 2,6-bisphosplmte also makes FBPasel more sen- sitive to inhibitécn by another aiiosteric reguiator. AMP. {c} Summary of reguiatien by F268P. A hormone cascade in heart muscle stimulates glycolysis. Muscle does not perform gluconeogenesis. The glycolytic enzyme phosphofructokinase-l in heart muscle is under the control of the hormone epinephrine (adrenalin), but in a different way than in liver. If you become afraid and ready to run, the medulla of the adrenal gland on your kidney will excrete epinephrine, which will bind to B-adrenergic receptors in the membranes of your muscle cells. These B-adrenergic receptors with bound epinephrine will cause a G protein to release GDP and bind GTP. This activated G protein will release its y subunit, which has the bound GTP. The y subunit, bound to GTP, stimulates the membrane-bound enzyme, adenylyl cyclase to synthesize CAMP. The CAMP made by adenylyl cyclase will in turn bind to and stimulate protein kinase A. Q}; l G) HO CH—CHrNH— CH3 Epinephrine binds to its specific receptor. H 0/ Epinephrine The occupied receptor Gs5 (asubunit) moves Adenylyl cyclase CAMP Phosphorylation 0f causes replacement of to adenylyl cyclase catalyzes the ' ' " activates cellular proteins by the GDP bound .to GS and activates it. formation of CAMP. A PKA. *—-> PKA causes the by GTP, activating GS. cellular response to cyclic nucleotide epinephrine‘ FIGURE 12-42 Transduction of the epinephrine signal: the B- Phosphfldiestmse adrenergic pathway. The seven steps of the mechanism that couples binding of epinephrine (E3 to its receptor (Rec) with activation of adenyl- yl cyclase (AC) are discussed further in the text. The same adenylyl 5’-AMP ® cyclase molecule in the plasma membrane may be regulated by a cAMPis degraded, stimulatory G protein ((35), as shown, or an inhibitory G protein (Cg, reveming the activation of PKA. not shown). (3S and G; are under the influence of different hormones. Hormones that induce GTP binding to (3. cause inhibition of adenyl- yl cyclase, resulting in lower cellular [CAMP]. Heart muscle PFK-Z is an isozyme of liver PFK-Z. This means that it catalyzes the same reaction but has a different amino acid sequence. Liver PFK-Z has a different amino acid sequence from heart muscle PFK-Z. Both enzymes have the same pre-mRNA, but differential splicing of their messenger RNAs leads to different mRNAs. Liver PFK-Z is deactivated by phosphorylation. In contrast, heart muscle PFK-Z is stimulated by phosphorylation, and it has no fructose 2,6-bisphosphatase activity. Thus in the presence of adrenalin, PFK-l activity increases, and glycolysis is stimulated. Skeletal muscle glycolysis is not under hormonal control. (“if i A summary of the hormonal cascade that activates glycolysis in heart muscle is summarized below. The hydrolysis of GTP, CAMP, and phosphorylated PFK-2 are omitted for simplicity. The material in this section is not covered in your textbook. It comes from page 1058 of the Voet and Voet textbook, which you are not required to read. EPlNLEPHRlNE 12?: N E PH RINE‘ MDRENEKMC R£CEPTOK L 6 £430th 6' PRQTEW GDP GT? G~DP WP ADENYLYL CYCLASE ACT/VRTION ATP-é cHMP +PH; INACTWE PROTEIN KINRSE A % ACTIVE PROTEIN KINASEA l + CAMKREGMATOR‘I SUBUNITS INACTNE PFK'l ACTIVE PFK—ZZ-P ATP ADP FfluCT05£ L-f’ FROLCTO5£36~8£5P ATP ADP lSTlMlll-P‘TES WH— J, MORE ACTNE GLYCoL‘ISLS PA&{‘ 10 Thus the hormone cascade that turns on glycolysis in heart muscle can turn off glycolysis in liver and stimulate gluconeogenesis. A comparative summary of the effects of the hormone cascade on glycolysis in heart muscle and glycolysis/gluconeogenesis in liver is shown below. HEART MUSCLE(ADRENALINE) LIVER (GLUCAGON) ACTIVE PROTEIN KINASE A ACTIVE PROTEIN KINASE A GIVES ACTIVE PFK-2 GIVES INACTIVE PFK-2 AND ACTIVE FRUCTOSE WHICH MAKES 2,6-BISPHOSPHATASE FRUCTOSE 2,6 BIS-P FRUCTOSE 2,6-BISPHOSPHATE IS HYDROLYZED J1 WHICH ACTIVATES PFK—l IS NOT STIMULATED PFK-l GLYCOLYSIS SLOWS 1/ WHICH ACTIVATES GLUCONEOGENESIS INCREASES GLYCOLYSIS BECAUSE FRUCTOSE 1,6- BISPHOPHATASE IS STIMULATED Terms and concepts Glucagon is a small peptide. Adenylate kinase Kms of hexokinase I and glucokinase Allosteric and hormonal control of glycolysis and gluconeogenesis in liver glycolysis in heart muscle glycogen synthesis and degradation in muscle and liver B-adrenergic receptor; glucagon receptor G protein Adenylyl cyclase Protein kinase A Phosphofructokinase-2 Fructose 2,6 bisphosphatase Liver FBPase-l is inhibited by fructose 2,6 bisphosphate. PFK-l is activated by fructose 2,6 bisphosphate To recognize Epinephrine 3’-5’ cyclic AMP fructose 2,6-bisphosphate GTP W11 Problems Study guide Chapter 15: Topics for Discussion 6-8 and 25. Here they are: 6. is AMP a more sensitive indicator of the cell’s energetic state than AT . 7. What is the reaction catalyzed by adenylate kinase? 8. What is the reaction catalyzed by protein kinase A (CAMP-dependent protein kinase? 25. How do ATP and ADP/AMP interact in the control of PFK-l. Problem A. What is the role of fructose 2,6-bisphosphate in the coordinate regulation of glucose and gluconeogenesis in the liver? Answers Study guide Chapter 15, Topics for Discussion 6. Adenylate kinase converts ADP to ATP and AMP to keep up the cell’s energy supply, so AMP is the sign of desperation. 7. 2 ADP (-9 ATP + AMP 8. Protein-serine + ATP -) Protein-serine-phosphate + ADP 25. ATP decreases the affinity of PFK-l for fructose 6-phosphate. AMP and ADP increase the affinity of PFK-l for fructose 6-phosphate. A. Fructose 2,6-bisphosphate activates PFK—l and inactivates FBPase—l. Pa? Glucagon is Coming Around To the tune of “Santa Claus is Coming to Town” You’ve gotta admire What molecules do Their cellular fire Is ready on cue Glucagon is coming around If hormone should bind Receptor outside G proteins find G nucleotides Glucagon is coming around They activate cyclases That make CAMPS Which bind to Protein Kinase A And remove the R’s from CS You’ve gotta admire What molecules do Their cellular fire ls ready on cue Glucagon is coming around Kevin Ahern, Oregon State University fa? 13 REGULATION OF CARBO- HYDRATE NETABOLIS 1. HEAD? AND M? RECULATE THE ENZYMES OF CARBOHYDRAj METABOLISM ALLOSTEKIC/ILD.’ QEAMP] IS MORE IMPORTANT THANIADP] IN SENSING THE STARVEDSTHTE, BECAuSE ADENYLATE KIN/13:; 3 HEXOKfi/BE? VAEEPAND MuSCLE HAVE DIFFERENT LIVER PERFORMS Km FOR GLUCOSE, ’BEmuSE GLuCONEOGENE SIS. LIVER SUPFLIES @Lucosz 70 um. WW Mu“ + HmUmasg DIFFER m'uvfli AND MUSCLE. .r ‘ HEXOKINASEI(MHSCLE) G ADENYLATE K’W‘SE \ CHICOSE WmucmE-H’ +an MD" 3MP”? FRHCTOSE FRucTosu-P 3 THETIC MHEXKINASEMLIVER) 1133mm GLuCOSf'r‘ATPeGLUCOSE-é-F+ADP L}. PHOS PHOFRUCTOKINHSE-l IS RECHLHT ED ALLOST-ERICALLY AND HORMOMLLY 5. GLYCOL YSIS IN HEART MMSCLE IS CONTROLLED DIFFERENTLY THAN IN LIVER, BECAUSE ONLY ' *' ' “GLUCOKINASE' Iggy HeonNnSE I K1,: and! AN!) {AMP} IS HmH. !( WM 13 THE BEST SENSOR >9 @LucoKmASE OF THE STARVED STATE; . Km‘lom" [GULCOSE MM LIVER FEEDS GLuCOSE T0 MHSCLE. EGu LATIOM 0F GLYCOLYIIS \5..\ I. ALLOSTERIC ’REGal—Anou (FEEDBACK INHIBITION) oF mg FIRST CoMMi'iTED ST 15? OF THE FIRST (OMHITE’ (PPR-1 CATAWZES "'5 “m STEP:PFK-1KEACTION. commrn’eb STEP 0F Hymns: If 15 NOT. PHRT OF ANOTHgR mm my. IT ’KELEASES -14 mm, GLYCOLYSIS 86LHCONEO- \8‘ “‘EB‘NTROLOFPYKWATE {r GENESISINTHEUVEK - e . - ARE REGULATEDRECIPKOCAUZY KINASE STOPS 301mm: By THE POLYPEPTIDE C0 MPOUNDS FROM ENTERING GLYCDLYSIS 6 ye ‘OLKMSEGL ' 3+? ML [Ram YCEKOL ' 9 RD" ‘ , NHDWF HORMONE GLUCAGON. PANCRERS Low gLOOD. .[cLu COSE] CLU’CAGON aw.) \ WP my? - i CASCADE 0F REACTIONS § Py u NEE!) AMPLIFIESLTHESIGNAL mm “M’s: "D" TGLUCONEOGENESIS ATP + Pmuwm; GLYCOLYSIS L TRANSDILCTION OFTHE \9 cm) o lo GLIICAGON SIGNAL = GLUCAGON t v . .. _ — I, OR 90000 fl ’ - ' fl TIIIIIITWI III '0' b. 9- W ‘ GTE @ ' ‘ ‘ 0 GDP ATP CYCLIC \ . CPMP- ASE I NILCLEOTIDE , ADENYLYL INCL 5 PHOSFIIQDIESTE - ASE : PHOSPHOKIILATIO mo- ’ "\' ' 5MP OF OTHER A $136; . w 0 ’ PROTEINS (m gis'cycucHAMP INACTIVE PROTEIN ' \11 « -(<;AMP) KIN/ISE II IKE] § \ ‘ I ,WTMP CANFCAMP . "H ATP Poi ‘ . ,FRucTosT; a» mum g ’ 1 mm” LOSES AtTTvITIé‘fIS ACTIVETEROAIDEPIN KINASEA ( migHPase—Q' , gorocu1 no {mm at, ‘ mam-.34 ENTT’ME . K; ‘b>I ,5"? 0‘2; 50014 Sam; 3' P03 ‘ I‘ a n I‘IORE OR FRIICTOSE éBISP FR , LESS ACTIVE '2 “"05”? WHICH GAINS ACTIVITY. Y3 FOR HEART MUSCLE: {5 H H O H3C-N-C—C / \ OH H A H ~ . 0H ADAENACINEAEPINEPHRINE , MADE A! THE ADRENAL a 3 u s MEDuLLA ON THE KIDNEY. I _ [Frc-G‘Plfin mus IN LIVER THE CLuCAwN ONE IS AFKALD ANDWW CASCADE Tum OFF READY TO RAN: GLYCOLYSIS. i EPINEPHRINE (Etc ivCLI’ACOSE é~THosPHATASE\ , EFINE‘PHMNERECEPTO? 9°"? GPROTElN-GTPfiGgPROTEINfiDP 1 ACTI'J’ , GDP (FTP ATP 90x Fr‘cL-P. mmglrED B wmas % m1 F8? 361 - ‘ V I: I (fit 15-35;) 0 Egg“ 2" ADENYLYL CYCLASE <) c CPR; L ACTIVE INACTNE GAP +DHAP le PROTEIN 1’ROTEIN i 4,896 KINASEA KINASIEA : i 9‘, PFKQ 7V» ACTIVE PFK-Q -P 3~PG [FRuCTOSELL'BtS—PT AT? RD? ' m ADP _ LP M CASCADE TURNS ON mom; RCTNE PFme—Z PFK-l PE DXALOAcéTm MORE ACTIVEGLYCOLYSIS PfRuvATE/ GLUCONEOGENES! HERRTMUSCLE LlVER WW \13 (EPINEPHRIND (GLUCAGON) a (cow SASHALL PEPTIDE ACTIVE PKR flCTQ/E FKA Aflfimg‘ VKINASE J, ; ACTIVE PFKJ INACTNEPFKJ , KMSOF HEXOKINHSEI AND _ CLuCOKINASE FRCEIL-BIS? nuosrmc ANDHOKMONRL 1 ‘ ¢ ‘ C3N0T559§ Eng aucon - PFK~1 *GLC L ' ~ ACTVEPFM mnchvs § GENES” m LIVER ACTIVE INACTIVE ~GLYCOLYSIS w HEHRTNUSQE GLYCOLYSIS CLYCOLYSIS, -gmoem METABOLISM ' GLuCONEOGENESlS 1N MuSCLEAND LIVER IS srmuLAT ED MDRENERGIC RECEPTOR W...— i G-PKOTHN BLOOD um I s W PROTEIN KINAS'E A (clllMP-\1 DEPENDENT PROTEIN W \3‘0 KINASE) . , 1 PM . 3~§cymcm1p F‘RWOSE l L BBPHOSPHAM mums]; ALBISPHOSPHRTE (FBPast) GTP LIVER FBPmi IS murerrgo BY mucrosxg 2,433.? W [S ACTIVATED BY WHOSE , 2.6 315 PHOSPHATE ALLOSTERIC ‘theumnow ms; CLYCOGEN PHOSPHORYLASE E DIFFERS IN musczj AND LIVER. § ...
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MCB102-4 - MCB102 Fall 2008 Regulation of glycolysis and...

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