Nucleosides and Nucleotides in the Diet

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In healthy adults, the normal diet is a good source of nucleic acids, nucleotides, and nucleosides, and no supplementation is necessary.

Pharmacological uses for nucleosides and nucleotides Oral uridine, as described earlier, can be used where de novo biosynthesis of pyrimidines is defective, and it may be useful in reversing some effects of mitochondrial dysfunction and to minimize the toxic effect of the antitumor drug 5-fluorouracil. Uridine is also a precursor for UDP-glucose, essential for the deposition of glycogen in the liver. Enzymes in the liver, however, rapidly degrade much of each oral dose of uridine. Oral administration of a new pro-drug, PN401, inhibits the degradative processes and delivers more uridine into circulation than oral uridine.

Oral CDP-choline is rapidly converted to its components, CDP (which can be recycled to uridine) and choline, an essential component of lipid membranes. Each molecule can then cross the blood-brain barrier, where CDP-choline is used in regeneration of membranes within and around nerve cells. Research in rats and early studies in humans suggest that its pharmacological effects may extend to protection against dementia, memory loss, visual degeneration, and recovery from ischemic strokes.

Beneficial effects of dietary nucleosides and nucleotides There is substantial evidence (principally from research in animal models) that the presence of nucleotides or nucleosides in the diet helps cellular proliferation in the gut, in postoperative trauma, and in the development of the immune response. Although dietary purines are not taken into circulation from the gut, purine nucleotides influence the transcription of several genes in intestinal cells. Nucleotides based on both adenosine and uridine can activate the purinergic receptors on a wide range of cell types. In lymphocytes and other cells, synthesis of nucleotides de novo is expanded dramatically when a signal for proliferation is received; the rate of pyrimidine biosynthesis increases more than that of purine biosynthesis. Thus, nucleotides are considered to be 'conditionally essential' since their provision in the diet will provide help through the salvage system where cells are dividing rapidly or where other nutrients, used as precursors, are scarce.

Human milk contains maternal cells, providing nucleic acids, and also nucleosides (particularly cytidine and uridine), and nucleotides equivalent to 10-20 mg/day. Cow's milk contains the de novo intermediate orotic acid, which can be taken up by erythrocytes and converted to UMP. Dietary nucleo-tides have been shown to promote the incorporation of essential fatty acids into membrane lipids in healthy newborn infants and to enhance the integrity and maturation of the intestine and of the immune system. Thus, these components may contribute to the improved immunity seen in breast-fed infants. Many infant formulas are now supplemented with nucleotides/nucleosides, but usually in lower concentrations than in human milk.

Purine ribonucleotides as flavor-enhancing additives The purine 5'-nucleotide monophosphates IMP and GMP, derived from degradation of RNA, have received much attention as the taste-active components in a variety of seafoods and meat. Both IMP and GMP enhance the umami flavor generated by monosodium glutamate (MSG). This flavor was generated only by the purine 5'-nucleotides, and not by the pyrimidine nucleotides CMP and UMP, by interaction with receptors on the specific umami tastebuds in the mouth. Since ATP is the major free nucleotide in muscle cells, its breakdown into the flavor-enhancing IMP provides a scientific rationale for the improved palatability of meat or game birds that have been hung for several days after slaughter. Similarly, the distinctive flavors of several cheeses are related to the metabolism, by bacteria, of the characteristic range of nucleotides present in the original milk.

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