glycogen biosynthesis - C arbohydrateMe tabolism Glycoge S...

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Unformatted text preview: C arbohydrateMe tabolism Glycoge S n ynthe sis S whe will carbohydratem tabolismtakeus o, re e t oday? Topics: Glycoge S n ynthe sis 1. 2. 3. 4. 5. 6. Glycoge conve nt & conde d e rgy source n: nie nse ne Whe doe it com from I s it always the ? re s e ? re Glycoge synthe pathway n sis Aside Two re d synthe m chanism using : late tic e s UDP-glucose Tissuediffe nce in glycoge synthe re s n sis Glycoge synthe and de n sis gradation arere gulate by d e nzym phosphorylation e (I nsulin vs. Glucagon) Why storefue as Glycoge rathe than l n r Fat? 1. Fat is not m obilize as quickly d 1. Fat cannot providee rgy unde anae ne r robic conditions 1. Fat cannot (e asily?) beconve d to glucoseto buffe blood rte r glucose(brain/ne urons) Why not storeglucosem onom r? e 1. S eam am ount of re rvewould re se quire0.4 M glucosein ce lls! 2. C lls would burst fromosm pre e otic ssure 3. Re rvein [glycoge se n] intrace llular is only ~ 0.01 uM 4. C s no osm pre ause otic ssureproble m Glycoge Facts…. n 1. A branche d-chain hom opolym r of D-glucose e 2. S ynthe re sis quire both ATP and UTP s 3. ~400 g glycoge in re n sting m uscle (1-2%we we t ight) 1. ~100 g glycoge in “fe live n d” r (6-8%we we t ight) 1. Norm accum ally ulate to the le ls & stops s se ve 2. S ingleglycoge m culeup to 100,000,000 Da n ole 3. Exists as granule in ce cytoplasm s ll 4. Granulecontains e nzym s f or both glycoge sis & glycoge e ne nolysis Glycoge n: Whe doe it com from I s it always re s e ? t he ? re Glucone ne can oge sis f e d into synthe of e sis glycoge n Glycoge store vary gre in fe vs. n s atly d starve ce d lls Glycoge le ls fluctuatewith fasting and n ve e ating Glycoge synthe pathway n sis Ove glycoge synthe rall n sis 1 2 S ps: te 1. I som rization; G6P -> e G1P (G1,6P inte e rm d.) 3 2. Activation by UTP 3. Glycoge prim nin ing 4 4. Exte nsion by Glycoge n S ynthase 5. Branching 5 6 6. Re at 4 & 5 pe Thee nzym s… e He xokinase / Glucokinase 0 Phosphoglucom utase 1 2 Glycoge nin UDP-glucose pyrophosphorylase 3 Glycoge S n ynthase 4 5 Glycosyl-(4->6) -transfe rase 6 Re actions of glycoge n synthe sis I nve e of: stm nt ole • 1 m UTP ole • 1 m ATP REM: UDP + ATP UTP + ADP nucle osideDP kinase “Activation” of glucoseby UTP is ne ssary ce f or synthe re tic actions 1 m e of ole q “ATP” inve d ste Re action is drive by subse nt hydrolysis of n que pyrophosphate *Note : • PPi hydrolysis has large ne gative∆ G, driving synthe sis s • UTP lose PPi, but re s UDP with P from form G6P Glycoge is a se nin lfglucosylating e nzym e covale links Glc to Tyr194 of ntly prote in Glycoge nin-Glc prim s the e 8 f unction of Glycoge S n ynthase Glycoge S n ynthasere action anom ric e carbon …can m 1->4 but not 1->6 (branch) linkage ake s Thebranching re action… • Glycosyl-(4->6)-transfe m s a largeline “chunk” to a rase ove ar branch position (C ) 6 ase nsity of polym r e • I ncre s de ase e .g llulose ) • I ncre s solubility of polym r (e vs. ce Glycoge and Glycoge nin n S ynthaseact in conce rt 1. 1 glucoseis transfe d to glycoge rre nin st 2. C ple form d with glycoge synthase om x e n 3. Elongate to line polym r (n=8) by glycoge d ar e nin 4. Glycoge synthasetake ove e nds and dissociate n s r; xte s f romglycoge nin 5. Branching occurs; glycoge synthasedissociate n s, glycoge re ains covale bound nin m ntly An aside Two re d synthe : late tic m chanism using UDP-glucose e s UDP-glucoseis also thestarting point for glucuronic acid t ransfe and ascorbic acid synthe r sis This e nzym is abse in e nt prim s, guine pigs, ate a som birds, som fish e e Galactoseaddition to glycoprote and ins Lactosesynthe (m m glands) usea m chanismsim to sis am ary e ilar glycoge synthe n sis At parturition Tissuediffe nce in glycoge re s n synthe sis Glycoge se s diffe nt n rve re purpose in live and m s r uscle Live blood sugar buffe r: ring (fre glucoseis m , e e ade xporte d) Muscle store fue : dl (no fre glucoseinte e e rm diate G6P is ; use d) Musclefibe synthe and storeglycoge during rs size n inactivity During activity use s: 1. fre glucose e 2. store glycoge d n 3. glucosefromthelive r (m obilize glycoge d n) “Fasting” doe NOT de te s ple m uscleglycoge for m we ks, n any e whe as e rcisede te it in re xe ple s hours! Brain ce lls/ne urons do not storeglycoge n Ge glucosefromthelive t r glycoge n Live re r sponds to high blood [glucose by synthe ] sizing glycoge n Exports glucoseto brain, m , RBC uscle ’s Live glycoge is de te r n ple d during a fast (> 24 h) Purposeof glycoge is for n blood glucosebuffe ring Glycoge synthe and de n sis gradation arere gulate by e d nzym e phosphorylation (I nsulin vs. Glucagon) m uscle live r * *I nsulin signalling pathway stim ulate glycoge synthe in s n sis both m uscleand live ce r lls A com x array of m cule affe Glycoge ple ole s ct n S ynthaseactivity P-ation/de P-ation cycleis re gulate by kinasecascade d …(late le r cture s) allows for re ciprocal re gulation of synthasevs. phosphorylase Be s e side ndocrinestim ulation (insulin), glucose re gulate glycoge m tabolismintrace s ne llularly in the live r I n he patocyte s, high [glucose has ne ] gative f e dback on glycoge e n de gradation; indire positive ct f e dback on glycoge e n synthe sis….(late r) You should know: 1. Advantage of glycoge as a store fue source s n dl 2. Glycoge structure& prope s (“facts”) n rtie 3. Re actions of glycoge synthe n sis 4. Role of the6 e s nzym s involve e d 5. How UDP-glucoseis use for lactose gluconurateand d , vitam Csynthe s in se 6. How tissue diffe in synthe and utilization s r sis 7. How glycoge synthe and de n sis gradation arere ciprocally re gulate d Te for this le xts cture : n ynthe I ” powe sis rpoint le ctureon we bsite • “Glycoge S lson ox hninge 3rd Edition. C r hapte 20, r • Ne & C (2000) Le pp. 735-739 (a littlethin) ham y ncott’s I llustrate d • C pe& Harve (1994) Lippe Re ws: Bioche istry, C vie m hapte 13, pp. 135-139 (on re rve r se in thelibrary) vlin xtbook of Bioche istry with C m linical • De (1997) Te C lations (Wile orre y-Liss), C hapte 7, pp. 312-327 (be r r tte f igure com s, plicate te ; on re rvein thelibrary) d xt se ...
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This note was uploaded on 10/07/2010 for the course DBT 446 taught by Professor Dd during the Spring '10 term at Indian Institute of Technology, Guwahati.

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