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Almost all cell types have the ability to synthesize purine and pyrimidine
nucleotides from low molecular weight precursors in amounts sufficient
for their own needs.
The de novo pathways are almost identical in all organisms.
Most organisms have the ability to synthesize nucleotides from
nucleosides or bases that become available through the diet or from
degredation of nucleic acids.
In animals, the extracellular hydrolysis of ingested nucleic acids
represents the major route by which bases become available.
4 !
blue-catabolism
red-salvage pathways
endonucleases:
pancreatic RNAse
pancreatic DNAse
phosphodiesterases:
usually non-specific
4
4
Enzyme inhibited by AMP, ADP, and GDP. In _ , expression is repressed
by PurR repressor bound to either guanine or hypoxanthine.
|
GTP used to make AMP,
ATP used to make GMP.
Also, feedback inhibition by
AMP and GMP.
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NDK also works with pyrimidine nucleotides and is driven by mass action.
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The three defects shown each result in elevated de novo purine biosynthesis
|
Severe HGPRT deficiency
()|
()
In addition to symptoms of gout, patients display severe behavioral
disorders, learning disorder, aggressiveness and hostility, including self-
directed. Patients must be restrained to prevent self-mutilation. Reason
for the behavioral disorder is unknown.
X-linked trait (HGPRT gene is on X chromosome).
1: carbamyl phosphate
synthase
2: aspartate
transcarbamylase
3: dihydroorotase
4: dihydroorotate DH
5: orotate
phosphoribosyl
tranferase
6: orotidylate
decarboxylase
7: UMP kinase
8: NDK
9: CTP synthetase
CAD=1,2,3
5 +6=single protein
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