ch_15_a_glikoliz_ve_heksozlarin_yikimi_yonca_duman
TRANSCRIPT
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In glycolysis (fromthe Greek glykys ,meaning "sweet,"and lysis , meaning"splitting"), a mole-cule of glucose is
of enzyme-cata-lyzed reactions toyield two mole-cules of the three-carbon compoundpyruvate.
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Glikoliz
Glukoz katabolizmasnn merkezi metabolik yolu(Birok hcrede karbon ak nn en fazla oldu u metabolik yol).
Baz memeli dokular ve hcreleri iin tek metabolik enerji kayna (eritrositler, bbrek medullas, sperm hcreleri, beyin).
Niasta depolayabilen baz bitki dokular (r. patates yumrular) vebaz suda ya ayan bitkiler (r. su teresi) iin enerjinin o unluklaretildi i metabolik yol.
Anaerobik mikroorganizmalarda enerji retimi btnyle glikolizebaml.
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Yeast Muscle
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Fermentation is a general term for the anaerobic
degradation of glucose or other organic nutrientsto obtain energy, conserved as ATP.
Because living organisms first arose in anatmosphere without oxygen, anaerobic breakdownof glucose is probably the most ancient biologicalmechanism for obtaining energy from organic fuelmolecules.
In the course of evolution , the chemistry of thisreaction sequence has been completely conserved;the glycolytic enzymes of vertebrates are closelysimilar, in amino acid sequence and three-dimensional structure, to their homologs in yeast and spinach .
Glycolysis differs among species only in thedetails of its regulation and in the subsequent
metabolic fate of the pyruvate formed.
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Glikoliz iin toplam reaksiyon:
Glukoz + 2 NAD + + 2 ADP + 2 P i 2 Pirvat + 2 NADH + 2 H + + 2 ATP + 2H 2O
(1) Ekzergonik olu um Glukozun pirvata dn m
Glukoz + 2 NAD + 2 Pirvat + 2 NADH + 2 H + 1G 146 kJ/mol =
(2) Endergonik olu um ATP ile P i den ATP olu umu
2 ADP + 2 P i 2 ATP + 2 H 2Oo
2G = 2 30.5 = 61 kJ/mol
o o ot 1 2G = G + G = -146 + 61 = -85 kJ/mol
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Pirvatta kalan enerji
Glukozun CO 2 ve H 2O ya komple oksidasyonu iin G = -2840 kJ/mol
Glukozun pirvata glikolitik ykm iin G = -146 kJ/mol
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9 Glikolitik ara rnHepsi de fosforillenmi tirGlukoz Pirvat
Fosforil gruplarnn nemli i levi vardr:
. .
membran elektrik ykl gruplara kar geirgen olmad ndan fosforillenmi rnlerhcre d na kamaz.
2. Fosforil gruplar metabolik enerjinin enzimatik korunumunda esas molekllerdir.
3. Enzimlerin aktif blgesine fosfat gruplarnn ba lanmasndan olu an ba lanmaenerjisi; enzimatik reaksiyonlarn aktivasyon enerjisini d rr, zgnl n arttrr.
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Baz bakteriler ve protistlerle tm bitkilerde :
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Substrate level phosphorylation
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(6) Gliseraldehit-3-P + P i + NAD + 1,3-bifosfogliserat + NADH + H +G = 6.3 kJ/mol
(7) 1,3-bifosfogliserat + ADP 3-fosfogliserat + ATP G = -18.5 kJ/mol
(T) Gliseraldehit-3-P + P i + NAD + ADP 3-fosfogliserat + ATP + NADH + H +
G = -12.5 kJ/mol
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Substrate level phosphorylation
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Glikolizin Toplam Denge Dkm
Glukoz + 2 ATP + 2 NAD + + 4 ADP + 2 P i 2 Pirvat + 2 ADP + 2 NADH + 2H +
+ 4 ATP + 2 H2O
Glukoz + 2 NAD + + 2 ADP + 2 P i 2 Pirvat + 2 NADH + 2 H + + 2 ATP + 2 H 2O
2 NADH + 2 H + + O 2 2NAD + + 2 H 2O
Karbon Yolu 1 mol glukozdan 2 mol pirvat
Fosforil Gruplar Yolu 2 ADP ve 2 P i den 2 ATPElektron Yolu 2 mol gliseraldehit-3-P tan 2 mol NAD +a 2 (:H ) olarak 4 elektron
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Glyceraldehyde-3-phosphatedehydrogenase
Phosphoglycerate kinase
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Glikolizde olu an pirvatn aerobik ko ullardaki sonu
2
2
5O 2 2
1/2 O+ +2Mitokondriyel Solunum
2 Pirvat 6 CO + 4 H
NADH + H NAD + H
O
O
+2
2 2
2 2 2
4 NADH 4 NAD 4 (1/2) O
FADH FAD (1/2) O
Pirvat 2 CO + 2 H 5 (1/2) OO
3
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Vigorously contarcted muscle consumes ATP produce ADP. Atp requirement of muscle replenished by the following reactions:
+2
Adenylate kinase
Mg2ADP ATP + AMP G 0
ATP
+2
rea ne nase
MgPCr + ADP Cr + ATP G 12.5 kJ/mol
When a sudden demand for energy depletes ATP, the PCr reservoir is used toreplenish ATP at a rate considerably faster than ATP can be synthesized bycatabolic pathways.
Cori Cycle
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Ethanol + 2 COEthanol + 2 COEthanol + 2 COEthanol + 2 CO 2222
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Alkol Fermentasyonu Toplam Denklemi
Glukoz + 2 ADP + 2 P i 2 Etanol + 2 CO 2 + 2 ATP + 2 H 2O
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Galactosemia
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Kas ve karaci er dokusunda
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glikolitik yol reglatr i levi
gren 4 enzim ierir:
1. Hekzokinaz,
2. Fosfofruktokinaz-1,3. Pirvat kinaz,
4. Glikojen fosforilaz.
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Yat kn hal (Steady-state)
Sabit hzda Sabit hzdabesin ve ener i atk rn
Canl
al salglanmas
HOMESTASIS
ATP i h l k i i l d
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ATP nin hcresel aktivitelerdemerkezi bir rol vardr. Hcrereglatr zellikleri olan katabolik
iin yksek bir yat kn hal(steady-state) konsantrasyonuyaratr.
(Enzim aktivitesi snrl)
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Bir biyokimyasal ya dametabolik yoldaki ak ;
(Enzim aktivitesi yeterince yksek)
katalizleyen enziminaktivitesine ba ldr.
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Her metabolik yol, hcre iinde onu katalizleyen enzimin d kaktivitesinden dolay en az bir tane denge konumundan uzak olanbir reaksiyon adm ierir. Bu reaksiyonun hz substrat varl ilede il, onu katalizleyen enzimin aktivitesi ile snrldr (Enzim
snrl reaksiyon ) .
Enzim snrl reaksiyonun hz metabolik yoldaki btn
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reaksiyonlarn hzn snrlad ndan o reaksiyonun oldu uadm metabolik yolun hz snrlayc admdr.
Hz snrlayc admlar olu turan reaksiyonlar hcreselou ar a rrevers ve et e zergon rea s yon ar r.
Bu reaksiyonlar katalizleyen enzimler de metabolikreglasyondaki hedef enzimlerdir ( reglatr enzimler ).
Metabolik Reglasyon
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g y
Hcrelerde metabolik kontroln ok hcreli organizmalardabirincil dzeyi ok hzl allosterik allosterik reglatrlerin konsan-enzim reglasyonu . trasyonlar hormonal kontrol
.
Hormon etkisi anahtar enziminaktivitesini de itirerek meta-bolik reglasyonu sa lar.
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Glukoz
Glikoliz (katabolik yol) Glukoneogenez (anabolik yol)
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Glikoliz (katabolik yol) Glukoneogenez (anabolik yol)
Pirvat
katalizlenir.
Katalitik ve anabolik ynde farkl enzimler tarafndan katalizlenen en az bir reaksiyonvardr. Bu enzimlerin katalizledi i reaksiyonlar: Ekzergoniktir, Irreversibldr, Enzim snrldr (substrat snrl de il), Hcresel ko ullardaki steady-state durumunda denge konumundan uzaktr, Enzimler ise reglatr enzimler dir.
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Comparison of thekinetic properties of hexokinase IV( l ki ) d
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(glucokinase) andhexokinase I. Note thesigmoidicity for hexo-kinase IV (hexokinaseD) and the much lower
m .When blood glucose risesabove 5 mM, hexokinaseIV activity increases, buthexokinase I is alreadyoperating near V max at 5mM glucose and cannot
respond to an increase inglucose concentration.
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Regulation of hexokinase IV (glucokinase) by sequestration in the nucleus.
The protein inhibitor of hexokinase IV is a nuclear binding protein that drawshexokinase IV into the nucleus when the fructose-6-phosphate concentration inliver is high and releases it to the cytosol when the glucose concentration is high.
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Regulation of pyruvate kinase. The enzyme is alIosterically inhibited by ATP, acetyl-CoA and long-chainfatty acids (all signs of an abundant energy supply), and the accumulation of frucrose-1,6-bisphosphatetriggers its activation. Accumulation of alanine, which can be synthesized from pyruvate in one step,allosterically inhibits pyruvate kinase, slowing the production of pyruvate by glycolysis. The liverisozyme (L form) is also regulated hormonally; glucagon activates cAMP-dependent protein kinase(PKA) , which phosphorylates the pyruvate kinase L isozyme, inactivating it. When the glucagon leveldrops, a protein phosphatase (PP) dephosphorylates pyruvate kinase, activating it. This mechanism prevents the liver from consuming glucose by glycolysis when the blood glucose concentration is low;instead, liver exports glucose. The muscle isozyme (M form) is not affected by this phosphorylation
mechanism.
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Cascade mechanism of epinephrineand glucagon action. By binding tospecific surface receptors, either
epinephrine acting on a myocyte (left)or glucagon acting on a hepatocyte(right) activates a GTP-bindingprotein (G ) Active G triggers a
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protein (G s ). Active G s , triggers arise in [cAMP], activating cAMP
binding protein kinase A (PKA) . Thissets of a cascade of phosphorylations;PKA activates phosphorylase b kinase,w c en ac va es g ycogen p os-phorylase. Such cascades effect a large
amplification of the initial signal; thefigures in pink boxes are probably lowestimates of the actual increase innumber of molecules at each stage of the cascade. The resulting breakdown
of glycogen provides glucose, which inthe myocyte can supply ATP (viaglycolysis) for muscle contraction andin the hepatocyte is released into theblood to counter the low blood glucose.
Glycogen phosphorylaseof liver as a glucosesensor. Glucose bindingto an allosteric site of the
phosphorylase a isozymeof liver induces a
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of liver induces aconformational change
that exposes itsphosphorylated Serresidues to the action of
phosphorylase a phosphatase 1 (PP1) .This phosphataseconverts phosphorylase ato phosphorylase b,sharply reducing the
activity of phosphorylaseand slowing glycogenbreakdown in response tohigh blood glucose.
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Glycogen phosphorylase of liver as a glucose sensor. Glucose binding to anallosteric site of the phosphorylase a isozyme of liver induces a conformationalchange that exposes its phosphorylated Ser residues to the action of phospho-
rylase a phosphatase 1 (PP1) . This phosphatase converts phosphorylase a tophosphorylase b, sharply reducing the activity of phosphorylase and slowing
glycogen breakdown in response to high blood glucose. Insulin also actsindirectly to stimulate PP1 and slow glycogen breakdown.