chapter 27
Nucleotide Metabolism
F IG U R E 2 7 -1 3
Structure of some of the purine nucleoside analogues used as antiviral agents.
mammalian enzymes by competition with dATP. Origi-
nally developed as an antileukemia drug, it has proved
useful in the treatment of herpes virus infections. Sev-
eral other purine nucleoside analogues are used as antivi-
ral agents (Figure 27-13); these include acyclovir, vala-
cyclovir, ganciclovir, penciclovir, and famiciclovir. After
conversion to their respective triphosphate derivatives,
these drugs inhibit viral DNA polymerase. Viruses inhib-
ited by these drugs are herpes simplex, varicella zoster,
cytamegalovirus, and hepatitis B. Antiviral agents that are
not purine nucleoside analogues are amantadine analogues
and a-interferon.
Inhibition of Conversion of Ribonueleoside
Diphosphate to Deoxyribonucleoside Diphosphate
an antineoplastic agent, acts by destroying
an essential free radical in the active center of ribonu-
cleotide reductase.
N — C — N H O H
An unexpected finding of hydroxyurea treatment is induc-
tion of hemoglobin F (HbF) production in red blood cells.
Hydroxyurea therapy results in an increase in both con-
tent and the number of red blood cells that contain HbF
(known as F cells). This property of hydroxyurea has been
used in the treatment of
sickle cell disease
because of the
antisickling effect of HbF (Chapter 28).
27.8 Catabolism of Purine Nucleotides
Degradation of purines and their nucleotides occurs during
turnover of endogenous nucleic acids and degradation of
ingested nucleic acids (Figure 27-11), during which most
of the purines are converted to uric acid.
Degradation of purine nucleoside phosphates (AMP,
5'-nucleotidase.(Figure 27-14) to produce adenosine, ino-
sine, guanosine, and xanthosine, respectively, and phos-
phate. Adenosine is converted to inosine by adeno-
sine deaminase (adenosine aminohydrolase). For inosine,
guanosine, and xanthosine, the next step is catalyzed by
purine nucleoside phosphorylase and involves a phospho-
rylation and a cleavage to produce ribose
-phosphate and
hypoxanthine, guanine, and xanthine, respectively. (The
enzyme also acts on deoxyribonucleosides to release de-
oxyribose 1-phosphate.) The pentose sugars are metab-
olized further or excreted. Purine nucleoside phosphory-
lase functions in purine salvage, and deficiency of this
enzyme results in decreased cell-mediated immunity. Hy-
poxanthine and guanine are converted to xanthine by xan-
thine oxidase and guanine aminohydrolase, respectively.
Thus, all purine nucleosides produce xanthine. Xanthine
oxidase is very active in the intestinal mucosa and the
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