Colchicine: A tricyclic, water-soluble alkaloid isolated from the autumn
crocus. Colchicine will inhibit microtubule formation and inhibit phago-
cytosis of urate crystals, thus preventing the inflammatory events asso-
ciated with a gouty attack.
Gout: An inflammatory event triggered by the crystallization of sodium
urate crystals in the joints as a result of increased levels of sodium urate
in the blood.
HGPRT: Hypoxanthine-guanine phosphoribosyltransferase; the enzyme
that catalyzes the synthesis of inosine monophosphate (IMP) and guano-
sine monophosphate (GMP) from hypoxanthine and guanine, respec-
tively. It makes up part of the purine salvage pathway, a way of recycling
purine bases back to the nucleotides.
Lesch-Nyhan syndrome: A genetic disease caused by a deficiency in
HGPRT that is characterized by mental retardation and self-destructive
behavior. Lesch-Nyhan patients have increased levels of uric acid and
sodium urate that lead to gout and kidney stones.
Purine salvage pathway: The synthesis of purine nucleotides by the con-
densation of the purine bases with phosphoribosyl pyrophosphate. As
the name suggests, it is a way in which purine bases can be recycled
back to nucleotides. The purine salvage pathway consists of two
enzymes, HGPRT and adenine phosphoribosyltransferase (APRT).
Uric acid: The final product in the degradation of purine nucleotides in
human metabolism. The salt form of uric acid, sodium urate, is present
at about saturation levels in the bloodstream. When sodium urate levels
increase above this point, it can crystallize into sharp crystals, usually in
the joints where the temperature is lower.
Xanthine oxidase: The enzyme that catalyzes the final steps in purine
degradation to produce urate. This enzyme is inhibited by compounds
such as allopurinol in treatment regimens designed to decrease sodium
urate concentrations in the blood.
Purine bases are used in many important biological processes including the
formation of nucleic acids (ribonucleic acid [RNA] and deoxyribonucleic acid
[DNA]), energy currency (adenosine triphosphate [ATP]), cofactors (nicoti-
namide adenine dinucleotide [NAD], flavin adenine dinucleotide [FAD]), and
cellular signaling (guanosine triphosphate [GTP], ATP, adenosine). Purines are
both synthesized
de novo
and taken in through the diet. Their degradation is a
ubiquitous process; however, increased levels of the enzymes that carry out the
metabolism of purine bases suggest that purine catabolism is higher in the liver
and the gastrointestinal tract. Abnormalities in purine biosynthesis and degrada-
tion are associated with numerous disorders suggesting that the regulation of
purine levels is essential.
Degradation of purine nucleotides, nucleosides and bases follow a common
pathway (Figure 43-1). During purine catabolism, the purine nucleotides
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