620
chapter 27
Nucleotide Metabolism
PRPP synthetase
In this reaction, the pyrophosphate group of ATP is trans-
ferred to ribose 5-phosphate; the product PRPP is a
high-energy compound. PRPP synthetase has an abso-
lute requirement for inorganic phosphate
(P i),
which func-
tions as an allosteric activator. The enzyme is inhibited
by many nucleotides, the end products of the pathway
for which PRPP is an essential substrate. The gene for
PRPP synthetase is located on the X chromosome. Mu-
tations in this gene have given rise to PRPP synthetase
variants with increased catalytic activity, which leads
to overproduction of uric acid (discussed below, under
“Gout”). The ribose 5-phosphate needed comes from three
sources:
5-phosphate produced in this pathway is converted to
ribose 5-phosphate as follows:
epimerase
D-Xylulose 5-phosphate------- >
isomerase
D-Ribulose 5-phosphate--------
>
D-ribose 5-phosphate
The contribution of this pathway to the supply of
ribose 5-phosphate may be a minor one. The
epimerase and isomerase are the same enzymes that
participate in the pentose phosphate pathway.
3.
Glycolysis.
Ribose 5-phosphate can also be produced
from intermediates of glycolysis (Figure 27-6). The
enzymes involved are those of the nonoxidative phase
of the pentose phosphate pathway, that occur in many
tissues.
27.3 Biosynthesis of Purine Nucleotides
Purine nucleotides can be produced by two different path-
ways. The salvage pathway utilizes free purine bases and
converts them to their respective ribonucleotides by appro-
priate phosphoribosyltransferases. The
de novo
pathway
utilizes glutamine, glycine, aspartate, N'°-formyl FH4,
bicarbonate, and PRPP in the synthesis of inosinic acid
(IMP), which is then converted to AMP and GMP.
1.
The pentose phosphate pathway.
This pathway is
probably the major source of ribose 5-phosphate in
liver and in bone marrow.
2. The
uronic acid pathway
(Chapter 15). Xylulose
De Novo
Synthesis
The atoms of the purine ring originate from a wide vari-
ety of sources (Figure 27-7). C
2
and Cg are derived from
G lu cose
(G lycolysis)
/
%
*
«
Fructose
6
-phosphate + G lyceraldehyde 3-phosphate
J
T ransketolase
Erythrose 4-phosphate + Xylulose 5-phosphate
' T ransaldolase
S ed oh ep tu lose 7-ph osp h ate + G lyceraldehyde 3-phosphate
Transketolase
R ibose 5-phosphate
2(R ibose 5-phosphate)
+ Xylulose 5-p h o sp h a te-
____________Isom erase
E pim erase
• 2(R ibulose 5-phosphate)
Sum:
2(Fructose
6
-phosphate) + G lyceraldehyde 3-phosphate ------ ►
3{R ibose 5-phosphate)
FIGURE 27-6
Synthesis of ribose 5-phosphate from intermediates of glycolysis by enzymes of the nonoxidative phase of the pentose
phosphate pathway. (See Chapter 15.)
