Purine nucleotide biosynthesis

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Nucleotide biosynthesis
Base Nucleoside Nucleotide
(base ribose) (nucleoside phosphate) Adenine
Adenosine AMP (adenylic acid
or adenosine monophosphate) Guanine
Guanosine GMP (guanylic acid
or guanosine monophosphate)
Uracil Uridine UMP (uridylic acid
or uridine
monophosphate) Thymine Thymidine TMP
(thymidylic acid or
thymidine monosphosphate) Cytosine Cytidine
CMP (cytidylic acid
or cytidine monophosphate)
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Purines
Adenine is 6-aminopurine.
Guanine is 2-amino-6-oxopurine.
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Purine biosynthesis was investigated by John
Buchanan (University of Pennsylvania and MIT)
and Robert Greenberg (University of Michigan) in
the 1940s.
Buchanan fed labelled precursors to pigeons and
analysed their incorporation into urate.
Birds excrete excess nitrogen as urate (a purine).
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The sequence of precursors that contribute ring
atoms is
Glutamine Glycine Formyl-THF Glutamine
CO2 Aspartate Formyl-THF
All contribute one ring atom except glycine which
contributes 3.
The purine ring is built up on a ribose sugar
that is derived from PRPP.
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The order in which ring atoms are added is 9
4 5 7 8 3
6 1 2
Q G For Q
CO2 D For
Ribose-P
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Sulfonamide antibiotics inhibit folate
biosynthesis and block purine biosynthesis. They
cause bacteria to accumulate a biosynthetic
intermediate.
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Outline of purine biosynthetic pathway.
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9
Inosine monophosphate
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Q 9
G 457
For 8
Q 3
CO2 6
D 1
For 2
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Four ATP molecules are used up during
construction of each IMP, mostly for activation
steps.
The intermediate 5-amino imidazole 4-carboxamide
ribonucleotide is equivalent to the remains of
AMP after the N1-C2 fragment is used for HIS
biosynthesis.
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IMP is converted to AMP or GMP
IMP
AMP
GMP
XMP
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Glutamine is the source of amino groups for
conversion of XMP to GMP. GTP is required for
conversion of IMP to AMP. ATP is required for
conversion of IMP to GMP. This helps to balance
the concentrations of AMP and GMP in cells.
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