6folato b12
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Vitamina B12 e Folato
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Vitamine idrosolubili
Assunte con la dieta
Assorbite a livello intestinale
Vie metaboliche correlate
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Metabolismo di residui monocarboniosiSintesi di basi puriniche e pirimidiniche Sintesi di amminoacidi
Chemioterapia antibiotica Chemioterapia antitumorale
Processi di proliferazione e differenziamento cellulareEritropoiesi
Sviluppo e integrità del sistema nervosoSviluppo e mantenimento della guaina mielinicaSintesi di neurotrasmettitoriSviluppo del tubo neurale
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ACIDO FOLICO (Vit. B9)
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IL Tetraidrofolico THFVIENE FORMATO DALLADIIDROFOLATO (DHF) REDUTTASI THF E’ LA FORMA METABOLICAMENTE IMPORTANTE: DAL THF SI POSSONO FORMARE I DERIVATI DONATORI DI UNITA‘ MONOCARBONIOSE
DHF REDUTTASI
DHF
THF
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DAL THF si formano tutti i derivati
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SINTESI NUCLEOTIDI PURINICI
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SINTESI NUCLEOTIDI PIRIMIDINICI
N5,N10 MetilenTHF Timidilato sintasi
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Timidilato sintetasi
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DERIVATI DELTETRAIDROFOLICO (THF)
THF
DHF REDUTTASI
UNITA’ MONO- CARBONIOSA+DiIDROFOLICO (DHF)
La riconversione in THF è indispensabile
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Diidrofolatoreduttasi
Diidrofolato
Tetraidrofolato
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DAL THF si formano tutti i derivati
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Omocisteina metiltransferasi
Vitamina B12(Metil)
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B12
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Metil B12
Omocisteina metiltransferasi
Timidilato sintetasi
DHF reduttasi
+NADP
NADPH dUMP
dTMP ANEMIA
X
X
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Anemia(Dal greco: senza sangue) è definita dalla caduta del tasso di emoglobina (Hb) nel sangue.Per l'uomo si definisce anemia una situazione di Hb <13 g/dl, per la donna Hb <12 g/dl.Nella definizione si possono usare anche altri parametri, quali l'ematocrito (M Hc<40%; F Hc<37%), o il numero di globuli rossi.Hb e Hc sono correlati e determinanti per la diagnosi di anemia, mentre poco sensibile è il numero degli eritrociti.
GLOBULI ROSSI (RBC) Ematocrito (Ht): M. = 40-52%
F. = 36-48%Emoglobina (Hb) :media = 14.5 g/dl
M. = 13.2-17 g/dlF. = 12- 15.5 g/dl
Eritrociti (numero) : M. 4.5 - 6 (x 106/L) F. 4.2 - 5.2 (x 106/L)
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Anemia
Da carenza di Folato Da carenza di B12
Non si formano derivati del THF Non si ricicla Met THF (trappola dei metili)
Non si sintetizza DNA Non si sintetizza DNA
Anemia Anemia
Risolta da somministrazione di Risolta da somm. B12 Acido Folico (Si formano derivati del THF) Apparentemente e
temporaneamente risoltada somm. Acido Folico (Si formano derivati del
THF)
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CARENZA DI B12
Metil-Malonil CoA Succinil CoA
AcetilCoA Malonil CoA Acidi grassi Mielina(-)
Acidi grassidispari
CARENZA DI B12 E DEMIELINIZZAZIONE
X
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Acido Folico
Chemioterapia antibiotica
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svg
SULFAMIDICI P-amminobenzoico
NH2
COOH
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SulfamidicoSostituisceP-aminobenzoato
Sintesi acido folico nei batteri
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Acido Folico
Chemioterapia antitumorale
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Timidilato sintetasi
FdUMP
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FdUMP
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Diidrofolatoreduttasi
DHF
THF
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Acido Folico
Neurodegenerazione
Difetti del tubo neurale
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• Complicazioni del sistema nervoso - Vari tipi di paralisi - Difficoltà di controllo della bile e dell’intestino– Disabilità di apprendimento– Depressione– Allergia alla gomma– Problemi sociali
Spina Bifida La spina non si chiudeCausa una lesione ai nervi
Intervento ChirurgicoRiduce rischi di infezione e ulteriori danni alla spina Trattamento per tutta la vita
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Acido Folico
Neurodegenerazione
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Livelli di folato più bassi nel siero di pazienti AD vs. controlli sani age-matched (p<0.02)
I livelli di Omocisteina nel siero non sono significativamente differenti (p=0.16)
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Quanto folato e B12 bisogna introdurre ?
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RDA= 200 g die
IN GRAVIDANZA= 400 g die
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RDA= 2 g die