Purines comprise bases, nucleosides in association with ribose
or deoxyribose, and nucleotides with one or more added phosphate groups.
Purine nucleotides are essential cellular constituents. They are
the building blocks of the polynucleotides, DNA and RNA, and, under
the form of mononucleotides or of nucleosides, also intervene in
numerous cellular functions. Among these are energy transfer (eg, by
adenosine triphosphate [ATP]), metabolic regulation
(eg, by guanosine triphosphate [GTP]), and signaling
(eg, by adenosine). Purine metabolism can be divided into three
pathways (Fig. 168-1):
Pathways of purine metabolism. (1) PRPP (phosphoribosylpyrophosphate)
synthetase; (2) adenylosuccinate lyase (adenylosuccinase); (3) AICAR
transformylase; (4) IMP cyclohydrolase (3 and 4 form ATIC); (5)
adenylosuccinate synthetase; (6) AMP deaminase; (7) 5′-nucleotidase(s);
(8) adenosine deaminase; (9) purine nucleoside phosphorylase; (10) hypoxanthine-guanine phosphoribosyltransferase;
(11) adenine phosphoribosyltransferase; (12) adenosine kinase; (13)
guanosine kinase; (14) xanthine oxidase (dehydrogenase); (15) guanine
deaminase. Enzyme defects are indicated by solid bars. AICAR, aminoimidazolecarboxamide
ribotide; AMP, adenosine monophosphate; ATIC, 5-aminoimidazole-4-carboxamide
ribonucleotide formyltransferase/IMP cyclohydrolase; FAICAR, formylaminoimidazolecarboxamide
ribotide; GMP, guanosine monophosphate; IMP, inosine
monophosphate; P, phosphate; PRPP, phosphoribosyl
pyrophosphate; S-Ado, succinyladenosine; SAICAR, succinylaminoimidazolecarboxamide
ribotide; S-AMP, adenylosuccinate; XMP, xanthosine
1. The biosynthetic pathway, starts
with the formation, often termed de novo, of the
high-energy compound phosphoribosyl pyrophosphate (PRPP) and leads
in 10 steps to the synthesis of the nucleoside monophosphate inosine
monophosphate (IMP). From IMP, two reactions lead to the formation
of adenosine monophosphate (AMP). Subsequently, the nucleoside di-
and triphosphates ADP and ATP and their deoxy counterparts are synthesized.
Two other reactions convert IMP into GMP, from which GDP, GTP, and
their deoxy counterparts are formed.
2. The purine catabolic pathway starts from the
nucleoside monophosphates GMP, IMP, and AMP and produces uric acid,
a poorly soluble compound that tends to crystallize once its plasma
concentration increases above 6.5 to 7.0 mg/dl (0.38–0.47
3. The purine salvage pathway utilizes the purine
bases guanine, hypoxanthine, and adenine, which are provided by
food intake or the catabolic pathway, and reconverts them by phosphoribosylation
into GMP, IMP, and AMP, respectively. It also utilizes the purine
nucleosides adenosine, guanosine, and their deoxy counterparts by
phosphorylation into the corresponding monophosphates, catalyzed
Inborn errors of purine metabolism comprise errors of purine
nucleotide synthesis, of purine catabolism, and of purine salvage. They
should be considered in patients with hyper- or hypouricemia, kidney
stones, and a variety of muscle, neurological, and other symptoms
(Table 168-1). The deficiencies of adenosine
deaminase and purine nucleoside phosphorylase, two
purine catabolic enzymes, cause severe combined immunodeficiency
(SCID; see Chapter 188). Adenosine deaminase
superactivity causes hemolytic anemia. The deficiency of deoxyguanosine
kinase causes a mitochondrial disease. The
deficiency of thiopurine methyltransferase is of importance
Table 168-1. Main Presenting Clinical Signs and Laboratory Data in Inborn Errors ...
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