GLUCONEOGENEZA GLUCONEOGENEZA Glicogenul hepatic acoper necesarul de G pt 10-18 ore n absena aportului de CH GNG este sinteza G din precursori neglucidici pe o cale metabolic special ce implic E mitocondriale i citosolice Are rol n meninerea glicemiei

90% din GNG are loc n Fi pe parcursul nopii (aport alimentar ntrerupt), 10% n Ri Dac sistarea aportului alimentar se prelungete: 40% din G va fi neosintetizat n Ri SUBSTRATURILE GNG

Molecule mici care prin prelucrare conduc la sinteza de G: intermediari ai glicolizei i ai c. Krebs Glicerolul, lactatul i - cetoacizii rezultai din dezaminarea AA glucogeni A. GLICEROLUL rezult din hidroliza TAG din esutul

adipos i este transportat pe cale sangvin la nivelul Fi fiind fosforilat n prezena glicerol-kinazei la glicerol-fosfat ce va fi oxidat la DHAP (intermediar glicolitic) Adipocitele nu pot fosforila glicerolul deoarece nu conin glicerol-kinaza SUBSTRATURILE GNG

SUBSTRATURILE GNG B. Lactatul eliberat n circulaie din muchiul striat n efort i de celulele lipsite de mitocondrii ( eritrocitele) SUBSTRATURILE GNG C. Aminoacizii rezultai prin hidroliza proteinelor sunt pp surs de G jeun - cetoacizii (OAA, - cetoglutaratul derivai din metabolizarea

AA glucogeni) ptrund n ciclul citric i formeaz OAA, precursor direct al PEP (decarboxilare) Acetil-CoA i precursorii acesteia (acetoacetatul, lizina i leucina) nu particip direct la sinteza G ( reacia catalizat de PDH este irev. ); genereaz corpi cetonici fiind compui cetogeni SUBSTRATURILE GNG

n sinteza G din lactat sau Py intervin 7 reacii glicolitice reversibile i 3 reacii reacii ireversibile ce tb scurtcircuitate prin 4 reacii favorabile energetic REACIILE SPECIFICE ALE GNG

A. Carboxilarea piruvatului n glicoliza: conversia irev. a PEP la Py n prezena PK n GNG: REACIILE SPECIFICE ALE GNG Py OAA

REACIILE SPECIFICE ALE GNG Piruvat-carboxilaza necesit legarea covalent a biotinei la gruparea - amino a unui rest de lizin formnd biocitina Intermediar R. are loc mitocondriile hepatice i renale; OAA= 1) S al

GNG sau 2) o surs ce poate compensa deficitul de intermediari ai c. Krebs; n miocite: OAA pt al 2-lea efect REACIILE SPECIFICE ALE GNG Reglarea alosteric Acetil-CoA activeaz piruvat-carboxilaza [Acetil-CoA ] intramitoc. determin sintezei de OAA ( jeun)

[Acetil-CoA ] piruvat-carboxilaza este inactiv, iar Py este oxidat n prezena PDH la acetil- CoA ce va fi oxidat n ciclul Krebs REACIILE SPECIFICE ALE GNG


OAA nu traverseaz direct MMI fiind redus la malat (MDH mitoc)ce va fi transportat din mitocondrii n citosol unde va fi reoxidat (MDH citosol.) REACIILE SPECIFICE ALE GNG PEPCK

Cuplarea celor 2 reacii este favorabil energetic pt PEP REACIILE SPECIFICE ALE GNG Defosforilarea Fr-1,6-difosfatului n prezena Fr-1,6difosfatazei scurtcircuiteaz reacia irev. a FFrK-1 cu formare de Fr-6-fosfat; reacie reglatorie important a GNG [AMPc] atest scderea rezervelor energetice i inhib Fr1,6-difosfataza [AMPc], [ATP] stimuleaz GNG [Fr-2,6-difosfat] i rezervele energetice reduse inhib Fr-1,6difosfataza

[Fr-2,6-difosfat] i rezervele energetice crescute stimuleaz Fr-1,6-difosfataza REACIILE SPECIFICE ALE GNG REACIILE SPECIFICE ALE GNG Defosforilarea G-6-fosfatului n prezena G-6-fosfatazei unteaz reacia ireversibil a hexokinazei fiind favorabil

energetic sintezei de G liber (Fi i Ri). REACIILE SPECIFICE ALE GNG REGLAREA GNG Depinde de : [glucagon] plasm ; [substraturi gluconeogenetice] GLUCAGONUL stimuleaz GNG prin 3 mecanisme: 1. Reduce [Fr-2,6-difosfat] cu activarea Fr-1,6-difosfatazei ;

inhibarea FFrK 2. Inducerea sintezei E: Glucagonul + transcripia genei pt PEPCK Insulina - transcripia genei pt PEPCK REGLAREA GNG

3. Modificarea covalent a activitii enzimatice [AMPc] + proteinkinaza AMPcdependent cu + PK inactive fosforilate rata de conversie a PEP la Py, cu orientarea spre GNG

REGLAREA GNG Disponibilitatea S AA glucogeni

Activarea alosterica a piruvat-kinazei hepatice exercitata de Acetil-CoA jeun (prin lipoliza cu -oxidarea AG in exces) cu orientarea spre GNG Inhibitia alosterica exercitata de AMP a Fr-1,6-difosfataza AMP + FFrK [AMP] + caile metabolice care oxideaza substantele nutritive in vederea obtinerii de energie

ATP si NADH rezultate din catabolism sunt necesare in GNG; -oxidarea AG: acetil-CoA ce + piruvat-carboxilaza GLICOLIZA


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