Page 195 - Color Atlas of Biochemistry
P. 195
186 Metabolism
Nucleotide degradation species. Thesameapplies to birds and many
reptiles. Most other animals continue purine
The nucleotides are among the most complex degradation to reach allantoic acid or urea
metabolites. Nucleotide biosynthesis is elab- and glyoxylate.
orate and requires a high energy input (see Pyrimidine (right). In the degradation of
p. 188). Understandably, therefore, bases and pyrimidine nucleotides (2), thefreebases ura-
nucleotides are not completely degraded, but cil (Ura) and thymine (Thy) are initially re-
instead mostly recycled. This is particularly leased as important intermediates. Both are
true of the purine bases adenine and guanine. further metabolized in similar ways. The pyri-
In the animal organism, some 90% of these midine ring is first reduced and then hydro-
bases are converted back into nucleoside lytically cleaved. In the next step, E-alanine
monophosphates by linkage with phosphori- arises by cleavage of CO 2 and NH 3 as the
bosyl diphosphate (PRPP) (enzymes [1] and degradation product of uracil. When there is
[2]). The proportion of pyrimidine bases that further degradation, E-alanine is broken
are recycled is much smaller. down to yield acetate, CO 2 ,and NH 3 . Propio-
nate, CO 2 ,and NH 3 arise in a similar way from
b-aminoisobutyrate, the degradation product
A. Degradation of nucleotides
of thymine(seep. 419).
The principles underlying the degradation of
purines (1) and pyrimidines (2) differ. In the
human organism, purines are degraded into B. Hyperuricemia
uric acid and excreted in this form. The purine The fact that purine degradation in humans
ring remains intact in this process. In contrast, already stops at the uric acid stage can lead to
the ring of the pyrimidine bases (uracil, thy- problems, since—in contrast to allantoin—uric
mine, and cytosine) is broken down into small acid is poorly soluble in water.When large
fragments, which can be returned to the me- amounts of uric acid are formed or uric acid
tabolism or excreted (for further details, see processing is disturbed, excessive concentra-
p. 419). tions of uric acid can develop in the blood
Purine (left). Thepurinenucleotide guano- (hyperuricemia). This canresult inthe accu-
sine monophosphate (GMP, 1)is degradedin mulation of uric acid crystals in the body.
two steps—first to the guanosine and then to Deposition of these crystals in the joints can
guanine (Gua). Guanine is converted by de- cause very painful attacks of gout.
amination into another purine base, xanthine. Most cases of hyperuricemia are due to
In the most important degradative path- disturbed uric acid excretion via the kidneys
way for adenosine monophosphate (AMP), it (1). A high-purine diet (e. g., meat) may also
is thenucleotidethatdeaminated, and inosine have unfavorable effects (2). A rare hereditary
monophosphate (IMP) arises. In the same way disease, Lesch–Nyhan syndrome, results from
as in GMP, the purine base hypoxanthine is a defect in hypoxanthine phosphoribosyl-
released from IMP. A single enzyme, xanthine transferase (A,enzyme[1]). Theimpaired re-
oxidase [3], then both converts hypoxanthine cycling of the purine bases caused by this
into xanthine and xanthine into uric acid.An leads to hyperuricemia and severe neurolog-
oxo group is introduced into the substrate in ical disorders.
each of these reaction steps. The oxo group is Hyperuricemia can be treated with
derived from molecular oxygen; another reac- allopurinol, a competitive inhibitor of xan-
tion product is hydrogen peroxide (H 2 O 2 ), thine oxidase. This substrate analogue differs
which is toxic and has to be removed by from the substrate hypoxanthine only in the
peroxidases. arrangement of the atoms in the 5-ring.
Almost all mammals carry out further deg-
radation of uric acid with the help of uricase,
with further opening of the ring to allantoin,
which is then excreted. However, the pri-
mates, including humans, are not capable of
synthesizing allantoin. Uric acid is therefore
the form of the purines excreted in these
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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