Lobonotomia

Nucleotide Degradation

Purine nucleotide degradation refers to a regulated series of reactions by which human purine ribonucleotides and deoxyribonucleotides are degraded to uric acid in humans.Two major types of disorders occur in this pathway. A block of degradation occurs with syndromes involving immune deficiency. myopathy or renal calculi. Increased degradation of nucleotides occurs withsyndromes characterized by hyperuricemia and gout, renal calculi, anemia or acute hypoxia. Management of disorders of purine nucleotide degradation is dependent upon modifying the specific molecularpathology underlying each disease state.

An explosion of information about disorders of purine nucleotide degradation in humans has occurred during the past 8 yr. The discovery of seven new enzymeabnormalities associated with specific clinical syndromes and the intensive research to elucidate the underlying molecular pathology have provided the basis for the major advances. New concepts haverelated tissue ATP levels and their depletion by hypoxic or metabolic mechanisms to common clinical abnormalities. Disorders of purine nucleotide degradation now encompass a range of previouslyunsuspected disease associations. Immunodeficiency, myopathy, renal calculi, hyperuricemia and gout, anemia, central nervous system dysfunction and tissue hypoxia occur with abnormalities of this biochemicalpathway. In this review, diseases of purine nucleotide degradation will be described. Two major types of disorders occur; blocks of purine nucleotide degradation and increased activity of thispathway. The metabolic basis underlying altered regulation of purine nucleotide degradation to uric acid in these diseases will be described as it is understood at the present time focusing on the morerecent advances.

REGULATION OF PURINE NUCLEOTIDE DEGRADATION

Purine nucleoside monophosphate derivatives are degraded to uric acid in humans by a final common pathway (Fig. 1). Complex regulation...