section 27.3
Biosynthesis of Purine Nucleotides
621
CQ,
Aspartate
cz>
N
-G lycine
N’°-Formyl FH,
j
c O \
<*,
| l'
s e - u â L N -Formyl FR,
C \ 9/
..
©
Amide nitrogen of glutamine
FIGURE 27-7
Sources of the atoms in
de novo
synthesis of the purine ring. The numbered
reactions correspond to the reaction steps in Figure 27-8.
N10-formyl FH
4
. Glycine is incorporated entirely and pro-
vides
C4, C 5 ,
and
N 7.
The a-amino group of aspartic acid
provides N
1
. The amide group of glutamine contributes
N
3
and N
9
. Carbon dioxide (or
HCO3
) provides Cô- The
stepwise synthesis of IMP is depicted in Figure 27-8. The
following features of purine biosynthesis should be noted.
1. The glycosidic bond is formed when the first atom of
the purine ring is incorporated (reaction
1
,
Figure 27-7). Free purines or purine nucleosides are
not intermediates of this pathway. In pyrimidine
biosynthesis, the pyrimidine ring is formed
completely before addition of ribose 5-phosphate.
2. The biosynthesis is accomplished by several
ATP-driven reactions. Ring formation (cyclization) is
achieved by incorporating nucleophilic amino groups
and electrophilic carbonyl groups at the appropriate
positions.
3. The first purine nucleotide synthesized is inosinic
acid (IMP), which is the precursor for the synthesis of
HC'
n r
a
-5-Phospho- D-ribosyl-
l-pyrophosphate
HO'
Î
-C.
H
jN
3 -5-Phosphoribosyl-
l-amine
ATP
T
HN'
'NH
v
©
CHO
Glutamine
*
+
ATP
5"-Phosphoribosyl-
glydnamide
D N -Formyl FH,
H
,N .
RÇ"
CH
'N H
P — R
P — R
P — R
5"-Phosphate-ribose
5"-Phosphoribosyi-
5-amino-4-imidazole-
carboxytate
Aspartic add
5 ‘-Phosphoribosyl-
5-aminoimidazole
COOH
I
o
CH,
II
HC— N H ^
C '
ATP
( + R O )
'CH
cooH
xx
/
VK
N
RN-
P — R
5'-Phosphoribosyl-5-
amino-4-imidazole-
succi nocarboxamide
HfT
C'
.
>
CH
5'-Phosphoribosyl- a-N-
foimylglydnamidine
N -Formyl
__FH,
©
5'-Phosphoribosyl- ot-N-
formylglydnamide
P — R
5"-Phosphoribosyl-5-
amino-4-i midazole-
carboxamide
OH
carboxamide
Inosine 5-phosphate
(inosinic add)
FIGURE 27-8
Biosynthesis of inosinic acid. The reactions are numbered. Enzymes: (1) amidophosphoribosyltransferase;
(2) phosphoribosylglycinamide synthetase; (3) phosphoribosylglycinamide formyltransferase;
(4) phosphoribosylformylglycinamidine synthetase; (5) phosphoribosylaminoimidazole synthetase;
(
6
) phosphoribosylaminoimidazole carboxylase; (7) phosphoribosylaminoimidazolesuccinocarboxamide synthetase;
(
8
) adenylosuccinate lyase; (9) phosphoribosylaminoimidazolecarboxamide formyltransferase; (10) IMP
cyclohydrolase.
