HMP Shunt-5.pptx

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    Hexose monophosphateshunt

    (HMP shunt)

    dr. Rauza Sukma Rita, Ph.D

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    Hexose monophosphate shunt(HMP shunt)

    Nama lain :

    Pentose shunt

    Pentose Phosphate Pathway Hexose monophosphate shunt

    Phosphogluconate pathway

    er!adi di sitosol

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    "alur alternati# untuk meta$olismeglukosa

    idak menghasilkan %P

    Dua #ungsi utama :

    Produksi N%DPH untuk sintesis redukti#,

    seperti $iosintesa asam lemak dankolesterol

    Produksi ri$osa untuk $iosintesis asam

    nukleat dan nukleotida

    Hexose monophosphate shunt(HMP shunt)

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    Hexose monophosphate shunt(HMP shunt)

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    N%DPHmerupakan

    $entuk #os#orilasidari N%DH

    Secara umum, N%DH

    $er#ungsi mendorong#os#orilasi %DPmen!adi %P.

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    &haracteristics:'xidati(e and Non)oxidati(e Phases

    'xidati(e phases Produksi N%DPH

    *rre(ersi$le

    Non)oxidati(e phases Produksi ri$ose)+)P

    Re(ersi$le reactions

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    + car$on atoms

    Regulatory enzyme

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    Regulatory enzyme

    nzim -PD sangat spesi/k terhadap N%DP0

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    Transketolase membutcoenzym thiaminepyrophosphate (TPP),

    Glikolisis

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    %lur H1P shunt dimulai dari glukosa )#os#at

    %lur ini terhu$ung kem$ali denganglikolisis karena dua dari produk akhirH1P shunt adalah glyceraldehyde 2)Pand #ructose )P3 dua produk ini nantinyaakan masuk kem$ali ke !alur glikolisis

    Hexose monophosphate shunt(HMP shunt)

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    Pengaturan HMP Shunt

    -lucose )phosphate Dehydrogenase 4-PD5merupakan enzim regulator

    N%DPH merupakan kompetiti# inhi$itor yangpoten terhadap enzim -PD

    6iasanya ratio N%DPH7N%DP0tinggi sehingga$isa mengham$at enzim -PD

    Namun, dengan meningkatnya permintaanterhadap N%DPH, ratio menurun dan dan

    akti/tas enzim -PD distimulasi. 8onsentrasi produk dan reaktan $isa $ergeser

    tergantung dari ke$utuhan meta$olik sel atau!aringan tertentu.

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    Sel yang mem$elah dengan cepatmem$utuhkan le$ih $anyak ri$ose +)

    phosphate dari N%DPH.

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    8e$utuhan akan N%DPH dan ri$ose +)phosphatedalam keadaan seim$ang

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    8e$utuhan akan N%DPH le$ih tinggidi$andingkan ri$ose +)phosphate, misal pada

    sintesis asam lemak di !aringan adiposa

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    Sel mem$utuhkan N%DPH and %P

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    Reduced

    glutathione

    -lutathione is atripeptide composedo# glutamate,cystein, glycine.

    Reduced glutathione

    4-SH5 maintains thenormal reducedstate o# the cell.

    Glutathione and NADPH

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    9ungsi -lutathione

    6erperan se$agai pereduksi 6erkonyugasi dengan o$at sehingga

    men!adi larut dalam air

    erli$at dalam transportasi asamamino melewati sel mem$ran

    &o#actor pada $e$erapa reaksienzimatik

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    -ugus sul#hydryl dari reducedglutahion4-SH5 $erperan mengurangiperoksida 4R'S5 yang ter$entuk selama

    transpor oxygen. Reacti(e oxygen species 4R'S5 merusak

    DN%, RN% dan protein sehingga $isamenye$a$kan kematian sel

    9ungsi -lutathione

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    -lutathione and rythrocytes )

    -SH is extremely important particularlyin the highly oxidizing en(ironment o#the red $lood cell.

    1ature Red 6lood &ells 4R6&s5 ha(e no

    mitochondria and are totally dependenton N%DPH #rom the pentose phosphatepathway to regenerate -SH

    *n #act, as much as ;< o# glucose

    consumption, $y erythrocytes, ismediated $y the pentose pathway.

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    -lutathione andrythrocytes )=

    he reduced #orm o# glutathione ser(esas a sul#hydryl $u>er.

    *t maintains cysteine residues inhemoglo$in and other proteins in a

    reduced state. -SH is essential #or normal R6&

    structure and keeping hemoglo$in in 9e00state.

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    -lutathione and

    rythrocytes )2 Reduced glutathione also detoxi/es

    peroxides.

    &ells with low le(els o# -SH aresuscepti$le hemolysis.

    *ndi(iduals with reduced -SH are su$!ectto hemolysis.

    his is o#ten clinically seen as $lack urineunder certain conditions.

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    -PD De/ciency

    xposure to anti)malarial drugs4Prima?uine5 results in increased cellularproduction o# superoxide and hydrogen

    peroxide 4Prima?uine sensiti(ity5 'ther chemicals known to increase

    oxidant stress Sul#onamides 4anti$iotic5

    %spirin and NS%*Ds @uinadine and ?uinine

    Napthlane 4moth$alls5

    9a(a $eans 4(icine A isouramil5

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    9a(a 6eans

    -rown worldwide *mportant in 1iddle

    ast

    High in protein -enetically modi/ed

    #a(a $ean $eingde(eloped

    Bow in (icine and

    isouramil

    9a(ism

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    9%C*S1

    *ndi(iduals with -PD de/ciency mustnot eat 9a(a $eans.

    rythrocytes lysedark or $lack urine.

    *nterestinghe growth Plasmodium #alciparum 4malaria

    parasite5 #ails in -PD de/cient indi(iduals.

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    TERIMAKASIH