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    METABOLISMUL:

    ASPECTE GENERALE

    Dr. Elena Petrescu

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    Tipuri de ci metabolice

    Degradarea oxidativ a combustibililor metabolici din diet i din depoziteletisulare (glucoz, acizi grai, aminoacizi)

    Stocarea combustibililor metabolici (n perioadele post-prandiale), respectiv

    mobilizarea rezervelor (n perioadele inter-prandiale)

    Biosinteza de molecule biologice avnd diverse roluri structurale ifuncionale

    Degradarea biomoleculelor cu rol structural sau funcional formare deprodui reziduali eliminai ca atare sau dup detoxifiere

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    Catabolism vs.anabolism

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    Etapele catabolismului

    combustibililor biologici

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    Rolurile diferite ale NADH / FADH2i NADPH formate n cursul catabolismului

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    Reglarea cilor metabolice

    Enzima cheie (reglatorie)catalizeaz etapa limitant de vitez:

    este reacia cea mai lent din ntreaga cale metabolic viteza sa determin vitezaglobal a cii

    are un caracter ireversibil (fiind puternic exergonic)

    este situat n prima parte a cii metabolice

    Mecanismele de control:

    - modificarea activitii sau a cantitii enzimelor cheie ajustarea vitezei reaciei pe

    care o catalizeaz => modificarea vitezei globale a cii metabolice

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    Reglarea independent icoordonat a cilor catabolice i anabolice

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    Mecanisme de reglare enzimatic

    I. Reglarea activitii moleculelor individuale de enzim

    Reglarea alosteric

    - metabolii din celul

    - NADH/NAD+sau ATP/ADP/AMP

    Reglarea covalent - influenat hormonal

    II. Reglarea cantitii enzimelor n celule

    Inducia i represia - aciuni hormonale (frecvent), uneori metabolii

    Tipuri particulare de reglare:

    Inhibiia feed-back

    Activarea feed-forward

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    Reglarea covalent a activitii enzimatice

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    METABOLISMUL GLUCIDIC

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    Structura glucidelor - aldoze

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    Structura glucidelor - cetoze

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    Ciclizarea glucozei

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    Ciclizarea fructozei

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    Tipuri de izomerie la monozaharide

    Izomeri D i L (enantiomeri)Epimeri

    Anomeri i

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    Dizaharide

    2 monozaharide unite prin legtur O-glicozidic

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    Polizaharideamidonul

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    Polizaharideglicogenul

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    Cile de metabolizare ale glucozei

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    GLICOLIZA

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    Glicolizatrsturi generale

    Scop: eliberarea parial a energiei coninute n molecula glucozei sintez de ATP

    Se desfoar n toateesuturile Localizat n citosol

    Poate funciona att n condiii aerobe, ct i anaerobe

    Ptrunderea glucozei n celule:

    transportorii din familia GLUT

    GLUT-1eritrocit i creier

    GLUT-2ficat, celulele pancreatice

    GLUT-4esut adipos i muscular

    (dependeni de insulin)

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    GLICOLIZAcele dou faze

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    Cele dou fazeale glicolizei

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    Formarea glucozo-6-P i metabolismul su ulterior

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    GLICOLIZAetapa consumatoare de energie

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    GLICOLIZAetapa generatoare de energie

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    Glicoliza aerob / anaerob i reoxidarea diferit a NADH

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    Rezultatele glicolizei aerobe

    Ecuaie global:glucoz + 2NAD++ 2ADP + 2Pi

    2 piruvat + 2NADH + 2H++ 2ATP + 2H2O

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    Glicoliza anaerob i reacia lactat dehidrogenazei

    Ecuaie global:

    glucoz + 2ADP + 2Pi

    2 lactat + 2ATP + 2H2O

    Importana reaciei LDH:

    Glicoliza poate funciona i poategenera ATP n condiii anaerobe

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    Glicolizaimportan particular pentruesuturile gluco-dependente

    Creierconsum energetic substanial satisfcut n cea mai mare parte pe seamaglucozei (NU poate degrada acizi grai)

    Eritrocitnu are mitocondrii nu poate degrada alte surse de energie (carenecesit desfurarea fosforilrii oxidative)

    Muchi scheletic n activitate susinutnecesar energetic disproporionat fa deaportul de oxigen mare parte din ATP este obinut prin glicoliza anaerob

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    Alte roluri ale glicolizei

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    Reglarea glicolizei

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    Reglarea PFK-1 de ctre F-2,6-P2

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    Reglarea piruvat kinazei

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    METABOLISMUL PIRUVATULUI

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    Ci de metabolizare a piruvatului

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    Decarboxilarea oxidativ a piruvatului

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    Complexul piruvat dehidrogenazei (PDH)

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    Componena complexului PDH

    Enzima Coenzime necesare Vitaminele din care provin

    Piruvat dehidrogenaza (E1) tiamin pirofosfat tiamina (vitamina B1)

    Dihidrolipoil transacetilaza (E2) acid lipoic acid lipoic

    coenzima A acid pantotenic

    Dihidrolipoil dehidrogenaza (E3) FAD riboflavina (vitamina B2)

    NAD+ nicotinamida (vitamina PP)

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    TPP (tiamin pirofosfat)

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    Acidul lipoic

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    Coenzima A

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    NAD+ FAD

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    Mecanismul decarboxilriioxidative a piruvatului

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    Reglarea activitii complexului PDH (PDC)

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    Bibliografie

    David L. Nelson, Michael M. Cox. Lehninger Principles of Biochemistry.5thedition, 2008.

    Colleen Smith, Allan D. Marks, Michael Lieberman. MarksBasic Medical Biochemistry: A ClinicalApproach.2ndedition, 2004.

    Robert K Murray, Darryl K. Granner, Peter A. Mayes, Victor W. Rodwell. Harpers IllustratedBiochemistry.27th edition, 2006.

    Pamela C. Champe, Richard A Harvey, Denise R. Ferrier. Lippincotts Illustrated Reviews Biochemistry. 4thedition, 2007.

    Reginald H. Garrett, Charles M. Grisham. Biochemistry.2ndedition, 1999.

    Mary K. Campbell, Shawn O. Farrell. Biochemistry.6thedition, 2007.