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chapter 27
Nucleotide Metabolism
N u cleop rotein s
P roteolytic e n z y m e s
A m ino a cid s
N u cleic a cid s
N u c le a s e s and
p h o sp h o d ie ste r a s e s
N u cleo tid es
N u cleo tid a se s, p h o s p h a ta s e s
^ — P h o sp h a te
N u c le o s id e s
f
P h o sp h a te
N u cleo sid e p h o sp h o ry la se
^ R i b o s e
1
-p h o sp h a te
F ree b a s e s
| X anthine o x id a se
Uric acid
(E xcreted in urine, or
ca ta b o lized by b acteria
in th e large intestine)
F IG U R E 27-11
Fate of dietary nucleoproteins. Only the predominant reactions are shown.
Dietary purines are mostly converted to uric acid.
polymerases, respectively. They are formed from the
monophosphates in two stages. Conversion to diphos-
phates is catalyzed by kinases. These enzymes are base-
specific but not sugar-specific. ATP is the usual source
of phosphate; in some cases, other triphosphates or dATP
may be used. Typical reactions are as follows:
guanylate kinase
GMP + ATP------------ ►
GDP + ADP
(dGMP)
(dGDP)
adenylate kinase
AMP + ATP ,
- ADP + ADP
The diphosphates are converted to the triphosphates by
the ubiquitous enzyme nucleoside diphosphate kinase. Re-
markably, the lack of base or sugar specificity applies to
the phosphate acceptor and the phosphate donor. Hence,
the general reaction is
nucleoside diphosphate kinase
dXDP + dYTP-----------------------►
+ dXTP + dYDP
(acceptor)
(donor)
Recall that conversion of ADP to ATP occurs mostly by
mitochondrial oxidative phosphorylation coupled to elec-
tron transport (Chapter 14).
converted to uric acid (Figure 27-11). Dietary nucleic
acids, present predominantly as nucleoproteins, are con-
verted in the small intestine to nucleic acids and protein
digestive products by the action of proteolytic enzymes
(Chapter 12). The liberated nucleic acids are depolymer-
ized to nucleotides by pancreatic nucleases and phosphodi-
esterases. The nucleotides are hydrolyzed to nucleosides
by nucleotidases and phosphatases. The nucleosides are
either absorbed or further cleaved to free bases by nucleo-
side phosphorylase. The free bases may be oxidized to uric
acid by xanthine oxidase. Nucleoside phosphorylase and
xanthine oxidase are very active in human small intestinal
mucosa. Uric acid produced in the small intestine may be
absorbed and excreted in urine, or it may be further ca-
tabolized by bacteria in the large intestine. In experiments
in which normal or gouty subjects ingested l
5
N-labeled
nucleic acids, the labeled purines were converted to uric
acid mainly by direct oxidative pathways without prior in-
corporation in tissue nucleic acids. Dietary purines (and
pyrimidines; see below) do not serve significantly as pre-
cursors of cell nucleic acids in the body.
27.4 Conversion of Nucleoside Monophosphates
to Diphosphates and Triphosphates
The
triphosphates
of nucleosides
and
deoxynucleo-
sides are substrates for RNA polymerases and DNA
27.5 Formation of Purine Deoxyribonucleotides
Conversion of ribonucleotides to the deoxy forms oc-
curs exclusively at the diphosphate level. Ribonucleo-
side diphosphate reductase (ribonucleotide reductase) cat-
alyzes the reaction. This enzyme is found in all species and
tissues. The immediate source of reducing equivalents is
the enzyme (E) itself in which two sulfhydryl groups are
oxidized to a disulfide. The general reaction is
Ribonucleoside diphosphate +
e (SH
) 2
ribonucleoside diphosphate
reductase
deoxyribonucleoside diphosphate + E(S-S) + H2o
In this reaction, the 2'-hydroxyI group of ribose is re-
placed by a hydrogen, with retention of configuration at
the 3'-carbon atom:
Thioredoxin-(SH)2
(reduced)
NADP+
Thioredoxin
reductase
Thioredoxin-(S-S)
(oxidized)
NADPH + H +
V
H20
