Significance of Nucleic Acids, Nucleotides, and Related Compounds In Infant Nutrition
Nucleotides are low molecular weight intracellular compounds that play major roles in physiological and biological functions. They act as precursors for nucleic acid synthesis and are also fundamental for intermediary metabolism. Nucleotides and nucleic acids turn over rapidly, especially in growing tissues or those undergoing constant cell renewal. Tissues that grow have a net formation of new DNA and a rapid turnover of RNA (1,2).
Nucleotides are typically conformed by a nitrogenous base (purine or pyrimidine), a pentose (ribose or deoxyribose), and one or more phosphate groups. The nitrogenous bases are derived from two parent heterocyclic molecules. The major purines found in living organisms are adenine and guanine, while cytosine, thymidine, and uracil are the major pyrimidine bases. Nitrogenous bases can be formed de novo from amino acid precursors or reutilized after their release from nucleic acid breakdown via the salvage pathway. The purine ring carbon atoms formed by de novo synthesis are derived from the dispensable amino acids glycine, glutamine, and aspartate. The carbon atoms for the de novo synthesis of pyrimidines are derived from carbamoyl phosphate and aspartate. Figure 1 summarizes the structure and precursors needed for the biosynthesis of purine and pyrimidine bases. The energy cost of de novo synthesis of nitrogenous bases requires significantly more energy than the salvage process, 5 mol of ATP as opposed to 1 mol of ATP for each nucleotide monophosphate produced; thus from an evolutionary point of view the salvage pathway has a selective advantage for rapidly growing organisms (3,4).
DIETARY NUCLEOTIDES: ABSORPTION AND METABOLISM
Dietary nucleotides are ingested mainly as nucleic acids and nucleoproteins derived from nuclear material. Digestion of nucleoproteins is initiated by proteases. Nucleic acids undergo partial hydrolysis in the stomach and are then subjected to pancreatic nucleases and phosphoesterases to yield nucleotides and nucleosides. Most of the DNA and RNA is fully hydrolyzed to nucleotides in the gut. Alkaline phosphatases in the enterocyte will cleave the phosphate groups in nucleotides to form nucleosides; nucleosidases will release the sugar moiety and hence the free nitrogenous bases (5,6). The evidence suggests that a mixture of nucleosides and nitrogenous bases is offered to the enterocyte for absorption. Transport studies using everted intestinal sacs and isolated perfused loops have demonstrated a highly efficient Na+ -dependent active transport system for nucleosides. Over 90% of the ingested nucleotides are absorbed, yet less than 5% are incorporated into intestinal nucleic acids and a relatively smaller amount appears in hepatic cells (7-9). Most of the absorbed purines are degraded to uric acid in the gut. The studies conducted to date have been performed under relative excess nitrogenous base supply and in mature adult animals. Whether these observations are applicable to earlier developmental stages remains undetermined (5).
