Download 26.9 Purines ond pyrimidines ,,,,,f sr`-c

26.9 Purinesand Pyrimidines
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26.9 Purinesond pyrimidines
AIMS: To show the link betweenomino ocids ond nucleicocids
in the body, Tonome the product of purine cotobolism
ond nome the diseosethot resultsfrom excessive
concentrotions
of this substonce
in the blood.
Many of the ring atoms of
pyrimidines and purines come
from amino acids.
Patients with high serum uric acid
concentrations may have to take
drugs for life to prevent development of hypertension or kidney
disease.The drugs act either by
preventing the formation of uric
acid or by increasingits rate of
excretion by the kidneys.
Organisms need to synthesizepurine and pyrimidine basesfor incorporation into the nucleic acids RNA and DNA. Moreover, nucleosides such as
adenosine are found as part of ATB cyclic AMf; CoA (coenzymeA), NAD+
(nicotinamide adenine dinucleotide), and FAD (flavin adenine dinucleotide). The atoms that constitute both pyrimidine and purine ring systems come from amino acids, ammonia, and carbon dioxide, as shovunfor
uracil and adenine in Figure 26.6.
The pathway of purine degradation is shorrrmin Figure 26.7. The end
product of this pathway is uric acid. Uric acid does not have a carboxyl
group, but it is an acidic compound because one of the hydrogens on its
five-membered ring readily dissociates. Human beings normally excrete
uric acid as a minor waste product in the urine. For reptiles and birds, uric
acid is the major form of excreted waste nitrogen. The white part of the
deposits that pigeons leave on statues in the park is almost pure uric acid.
Some people, almost always male, make too much uric acid or fail to
excreteit. Uric acid is quite insoluble, and it also readily forms an insoluble
sodium salt, sodium urate. In gout, uric acid or sodium urate exceedsits solubility in plasma and forms needle-likecrystalsthat are depositedin joints,
especiallyin the big toe. Gout attacks, which result in swelling and inflammation of the affected joint, are agonizinglypainful. Ralph, the accountant
in the Casein Point earlier in this chapter, has gout.
Lesch-Nyhan slmdrome, a genetic disease,is caused by the lack of an
enzymeneededto catalyze the synthesisof purines. At about 2 or 3 years of
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Figure26.6
Theatomsthatcomprise
pyrimidines
andpurinescomefromaminoacids.
The
figureshowsthe pyrimidineuracil(a) andthe pu.rine
adenine(b).
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CHAPTER
26 Metabolismof NitrogenCompounds
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Figure26.7
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hydrogen
Uric acid
age, Lesch-Nyhan victims begin to show an uncontrollable urge to bite
themselves.Unless they are forcibly restrained, some Lesch-Nyhan patients
will literally bite offtheir flngers and lips. This diseaseis rare; about 60 cases
are reported in the medical literature. Victims of the Lesch-Nyhan syndrome often show symptoms of gout. These s),Tnptomsare alleviated by
allopurinol, but there is no alleviation of the tendency for self-destruction.
Folrow-upro rHECnsrlt Poltr: A painful episode
Ralph's painful symptoms indicated gout, and a
blood test showed that he had elevated levels of uric
acid in his blood. The symptoms of gout may often be
relieved by a diet that restricts the intake of foods
high in purines, such as shellfish, bacon, beef, and
turkey. In severe cases, the drug allopurinoi ls sometimes effective.
Allopurinol prevents the synthesis of uric acid
by inhiblting xanthine oxidase, the enzyme that
xanthine
uric
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acid.
A low-purine diet and
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Ralph back on his feet.
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