purine nucleotide metabolism anabolism · 2020. 10. 28. · de novo biosynthesis: this is a main...
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Purine Nucleotide
Metabolism
Anabolism
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Purines And Pyrimidines
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Nucleoside and Nucleotide
Nitrogenous base Ribose
Nitrogenous base Ribose Phosphate
Nucleoside =
Nucleotide =
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Nucleotides
are
Building blocks
of
Nucleic acids
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pyrimidine purineOR
Riboseor
2-deoxyribose
N-b-glycosylbond
Structure of Nucleotides
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There are two pathways
leading to Biosynthesis of
Nucleotides
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De Novo Biosynthesis:
This is a main synthetic pathway.
The biosynthesis of
nucleotides begins /very new
with the use of small metabolic
precursors as a raw material:
Amino acids, Ribose-5-phosphate,
CO2, and One-carbon units.
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Salvage pathways:
The synthesis of nucleotide by
recycle of the free Nitrogen
bases or nucleosides released
from nucleic acid breakdown.
This is important in Brain and Bone
marrow
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De Novo Biosynthesis Of Purine Nucleotides
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Site Of
Purine Nucleotide
Biosynthesis:
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Predominantly In cytosol of Liver,
To some extent in small intestine and Thymus.
In humans, all necessary enzymes for Purine Nucleotide biosynthesis are found in the cytoplasm of the cell.
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Denovo biosynthesis occurs in most of the cells’ cytosol
Except human Brain, Polymorphonuclear leukocytes and Erythrocytes.
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Requirements For De Novo Biosynthesis of Purine Nucleotides
Purines are synthesized using 5PhosphoRibose (R-5-P) as the starting mateRequirements ForDe Novo Biosynthesis
PRPP (5-Phosphoribosyl-1-Pyrophosphate) is an active donor of R-5-P.
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Biosynthesis Of Pyrimidines Nucleotides
N
N
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Pyrimidine Nucleotide
Metabolism
There are also two synthesis
pathways of Pyrimidine
nucleotides:
Denovo Synthesis and Salvage
pathway.
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De Novo Synthesis Pathway
In De novo pathway the
Pyrimidine ring is assembled first
and then linked to Ribose
phosphate.
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The carbon and nitrogen atoms in the Pyrimidine ring are derived from:
Bicarbonate
Aspartate
Glutamine
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Salvage Pathway
The significance of salvage pathway :
Save the fuel.
Some tissues and organs such as brain
and bone marrow are only capable of
synthesizing nucleotides by salvage
pathway.
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Uric acid is waste excreted end product of
Purine catabolism.
The rate of uric acid excretion by the normal
adult human is about 0.6 g/24 h in urine.
The normal concentration of uric acid in the
serum of adults is in the range of 3-7 mg/dl.
Catabolism Of Purine Nucleotides
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Catabolism of Pyrimidine
Nitrogen Bases Cytosine and Uracil yields :
b-Alanine,
Ammonium ions
CO2
b-Alanine can be recycled into the synthesis of coenzyme A
Catabolism of Thymine yields:
b-Aminoisobutyric acid
Ammonium ions
CO2
Catabolism Of Pyrimidines
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H2OH2O
H2N CH2 CH2 COOH H2N CH2 CH COOH
CH3
N
NH
O
NH2
H2O NH3HN
NH
O
O
CH2
CH2NH2
NH
O
HOOC
HN
NH
O
O
CH3
CH2
CHNH2
NH
O
HOOC
CH3
cytosine uracilthymine
¦Â-ureidopropionate
¦Â-ureido-isobutyrate
CO2 + NH3
¦Â-alanine ¦Â-aminoisobutyrateHighly soluble
Products
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Principal differences
between metabolism of
Purines and Pyrimidines
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CharacterPurines
De Novo Synthesis
Pyrimidines
De Novo Synthesis
Number Of Steps
Involved11 Steps 6 Steps
Precursors Of Ring
Amino acids :Asp Gly and Gln
N10FormylTHF
CO2
Amino acids :Asp and Gln
CO2
Major Portion
Of Ring provided by
Glycine Aspartate
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CharacterPurines
De Novo Synthesis
Pyrimidines
De Novo Synthesis
Acquisition of Ribose-Phosphate In Starting Steps In End Steps
Formation of N-Glycosidic bond
In 1st step of their biosynthesis(PRPP is the 1st Substrate)
a heterocyclic ring is formed first, then it reacts with PRPP
products of degradation
Uric acid(poor solubility in H2O)
NH3
CO2, NH3, b-AminoIsobutyrate and bAla(soluble in H2O)
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CharacterPurines
De Novo Synthesis
Pyrimidines
De Novo Synthesis
Number Of ATPs
Involved6 ATPs 2ATPs
Nucleotide Produced in End
IMP UMP
Ring Closure
At 6 and 11 steps 3rd Step