curso de bioquímica 26-rescate de nucleótidos
TRANSCRIPT
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Catabolismo y Rescate de NucleótidosAntonio E. Serrano PhD. MT.Cátedra de Bioquímica - [email protected]
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Digestión de Acidos Nucleicos
• Ácidos nucleicos ingeridos en la dieta se degradan en nucleótidos por:• Nucleasas
pancreáticas• Fosfodiesterasas
intestinales• Nucleotidasas
Intestinales• Fosfatasas no
específicas degradan nucleótidos en nucleósidos
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Degradación de Purinas• Remoción secuencial
de partes• Producto Final es el
Ácido Úrico
XantinaOxidasa
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Degradacion de Purinas
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Catabolismo de Purinas• Xantina es el punto de
convergencia del metabolismo de las Bases purinas• La degradación de
Purinas de ribonucleótidos es la misma de las Purinas de desoxyribonucleótidos
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Catabolismo de Purinas
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Rescate de Purinas
Hipoxantinao
Guanina+ PRPP = IMP or GMP + PPi
Hipoxantinaguanosilfosforibosil transferasa(HGPRTasa)
Adenina + PRPP = AMP + PPi Adeninefosforibosil transferasa
(APRTasa)
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Metabolismo Purinas
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Catabolismo Intracelular de Purinas• Nucleotides broken into nucleosides by action of
5’-nucleotidase (hydrolysis reactions)• Purine nucleoside phosphorylase (PNP)• Inosine Hypoxanthine• Xanthosine Xanthine• Guanosine Guanine
• Adenosine is deaminated to Inosine (ADA)
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Catabolismo Intracelular de Purinas
• Xanthine is the point of convergence for the metabolism of the purine bases
• Xanthine Uric acid• Xanthine oxidase catalyzes two reactions
• Purine ribonucleotide degradation pathway is same for purine deoxyribonucleotides
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Degradacion de Xantosina
• Ribose sugar gets recycled (Ribose-1-Phosphate R-5-P ) – can be incorporated into PRPP (efficiency)• Hypoxanthine is converted to Xanthine by Xanthine Oxidase• Guanine is converted to Xanthine by Guanine Deaminase• Xanthine gets converted to Uric Acid by Xanthine Oxidase
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Uric Acid Excretion• Humans – excreted into
urine as insoluble crystals• Birds, terrestrial reptiles,
some insects – excrete insoluble crystals in paste form • Excess amino N converted to
uric acid• (conserves water)
• Others – further modification :
Uric Acid Allantoin Allantoic Acid Urea Ammonia
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Degradación de Pirimidinas• Anillos de Pirimidinas pueden
ser completamente degradados en estructuras solubles, al contrario de lo que ocurre con purinas que generan Ácido Úrico
• Pirimidinas pueden tambien ser rescatadas mediante reacciones con PRPP• Catalizadas por la Pirimidin
fosforibosiltransferasa• Las vías de degradación de las
purinas y pirimidinas son distintas pero las vias de rescate son similares
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Degradacion de Pirimidinas• CMP and UMP
degraded to bases similarly to purines • Dephosphorylation• Deamination• Glycosidic bond cleavage
• Uracil reduced in liver, forming b-alanine • Converted to malonyl-
CoA fatty acid synthesis for energy metabolism
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Catabolismo de Pirimidinas