CHAPTER
Nucleotide Metabolism
A nucleotide consists of a purine or pyrimidine base, a
pentose (or deoxypentose), and a phosphate. The synthe-
sis and degradation of nucleotides are discussed in this
chapter. Structural features of nucleotides were discussed
in Chapter 23 and how nucleotides are used in the synthesis
of DNA and RNA in Chapters 24 and 25, respectively.
Table 27-1 gives the nomenclature of purine and pyrimi-
dine nucleosides and nucleotides. Names of purine nucleo-
sides end in
-osine,
whereas those of pyrimidine nucleo-
sides end in
-idine;
guanine nucleoside is guanosine and
should not be confused with guanidine, which is not a
nucleic acid base; thymidine is a deoxyriboside.
Nucleotides are synthesized by two types of metabolic
pathways:
de novo
synthesis
and
salvage pathways.
The
former refers to synthesis of purines and pyrimidines
from precursor molecules; the latter refers to the conver-
sion of preformed purines and pyrimidines—derived from
dietary sources, the surrounding medium, or nucleotide
catabolism—to nucleotides, usually by addition of ribose-
5-phosphate to the base.
D e novo
synthesis of purines is
based on the metabolism of one-carbon compounds.
27.1
One-Carbon Metabolism
One-carbon moieties of different redox states are utilized
in the biosynthesis of the purine nucleotides and thymi-
dine monophosphate (also known as thymidylate), the
metabolism of several amino acids (particularly serine and
homocysteine), the initiation of protein biosynthesis in
bacteria and mitochondria by formylation of methionine,
and methylation of a variety of metabolites. These one-
carbon reactions utilize coenzymes derived from
folic
acid,
or
folate.
Folate is a vitamin for humans (and
other animals because of their inability to synthesize it)
(Chapter 38).
Folic acid is the common name for
pteroylglutamic
acid,
a compound consisting of a heterobicylic pteri-
dine, p-aminobenzoic acid (PABA), and glutamic acid
(Figure 27-1). The combination of the first two produces
pteroic acid. Humans lack the enzymes capable of syn-
thesizing PABA or of linking pteroic acid to glutamate.
The antimicrobial activity of sulfonamides is due to their
competitive inhibition of the bacterial enzyme that incor-
porates PABA into dihydropteroic acid (Chapter
6
).
Folates have a wide biological distribution; a rich di-
etary source is green leaves. They occur in nature largely
as oligoglutamyl conjugates (e.g., in plants, predomi-
nantly pteroylheptaglutamate) in which the peptide link-
ages occur between the у -carboxyl group of one gluta-
mate and the a-amino group of the next (Figure 27-1).
The mechanism of intestinal absorption of folate is not
completely understood. The ingested folylpolyglutamates
must be converted to folylmonoglutamate prior to absorp-
tion. The folylpolyglutamates are rapidly hydrolyzed in
the intestines at neutral pH by the brush-border enzyme
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