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The major site of purine synthesis is in the liver
Abstract: Dietary nucleotides have been reportedly beneficial, especially for infants, since they positively influence lipid metabolism, immunity, and tissue growth, development and repair. Rapidly proliferating tissues, such as the immune system or the intestine are not able to fulfil the needs of cell nucleotides exclusively by synthesis and they preferentially utilize the salvage pathway recovering nucleosides and nucleobases from blood and diet. In the present review we describe the modulatory effect of dietary nucleotides on the immune system together with some of their effects on gut-associated lymphoid tissue. Dietary nucleotides influence lymphocyte maturation, activation and proliferation. Likewise, they affect the lymphocyte subset populations in both the small intestine and blood. Moreover, they are involved in enhancing macrophage phagocytosis and delayed hypersensitivity as well as allograft and tumour responses. In addition, they contribute to the immunoglobulin response in early life, having a positive effect on infection. In fact the incidence and duration of acute diarrhoea is lower in infants fed supplemented-nucleotide formulas. The molecular mechanisms by which dietary nucleotides modulate the immune system are practically unknown. Dietary nucleotides have been shown to enhance the production and the genetic expression of IL-6 and IL-8 by foetal small intestinal explants. Dietary nucleotides may influence protein biosynthesis as well as signal membrane transduction mediated by the interaction of exogenous nucleosides and their receptors may also contribute to modulate the expression of a number of genes, some of which can directly affect the levels of intestinal cytokines.
Abstract: Nucleotides, nucleosides and nucleobases belong to the non-protein-nitrogen (NPN) fraction of milk. The largest amounts of ribonucleosides and ribonucleotides – ribose forms only were considered in this review – were measured directly after parturition in bovine milk and other ruminants as well as in the milk of humans. Generally, concentrations of most of the nucleo(t)ides tend to decrease gradually with advancing lactation period or nursing time. The species-specific pattern of these minor constituents in milk from different mammals is a remarkable property and confirms, at least, the specific physiological impact of these minor compounds in early life. The physiological capacity of these compounds in milk is given by the total potentially available nucleosides. The main dietary sources of nucleos(t)ides are nucleoproteins and nucleic acids which are converted in the course of intestinal digestion into nucleosides and nucleobases the preferred forms for absorption in the intestine. Thus, nucleosides and nucleobases are suggested to be the acting components of dietary and/or supplemented nucleic acid-related compounds in the gut. They are used by the body as exogenous trophochemical sources and can be important for optimal metabolic functions. Up to 15% of the total daily need for a breast-fed infant was calculated to come from this dietary source. Concerning their biological role they not only act as metabolites but are also involved as bioactive substances in the regulation of body functions. Dietary nucleotides affect immune modulation, e.g. they enhance antibody responses of infants as shown by a study with more than 300 full-term healthy infants. Dietary nucleos(t)ides are found to contribute to iron absorption in the gut and to influence desaturation and elongation rates in fatty acid synthesis, in particular long-chain polyunsaturated fatty acids in early stages of life. The modulation of cell proliferation and apoptosis has been described by ribonucleosides, in particular by modified components using human cell culture models. Due to the bio- and trophochemical properties of dietary nucleos(t)ides, the European Commission has allowed the use of supplementation with specific ribonucleotides in the manufacture of infant and follow-on formula. From the technochemical point of view, the ribonucleoside pattern is influenced by thermal treatment of milk. In addition ribonucleosides are useful indicators for quantifying adulterations of milk and milk products.
Molecular Biology | Biochemistry for Medics – Lecture …
Nucleotides have been identified as conditionally essential nutrients. As prevention studies, conducted with nucleotide-supplemented formula, have shown statistically significant decrease in the risk of diarrhea, we tested the hypothesis that the consumption of nucleotide-supplemented formula during an acute diarrhea episode is associated with therapeutic effects in the treatment of infants with acute diarrhea and dehydration. A randomized, double-blind, controlled clinical trial was conducted in which patients were randomly assigned to 1 of 2 treatment groups. The "test" group consumed a nucleotide-supplemented infant formula and the "control" group consumed a nonsupplemented formula. Infants were accommodated in a metabolic unit where body weight, and all intakes and outputs were recorded at 24-hour intervals during hospitalization. Laboratory parameters including blood gases and electrolytes were monitored during hospitalization. Eighty-one male infants ranging in age from older than 1 month and younger than 1 year, with acute non-cholera diarrhea and dehydration were studied. Primary outcomes were stool output and duration of diarrhea and did not differ significantly between the groups, with a stool output of 304.2 (SD 254.0) vs 350.3 (SD 269.1) g/kg and a duration of diarrhea of 83.3 (SD 44.5) vs 88.8 (SD 46.6) for the test and control groups, respectively. Anemia was highly prevalent and breast-feeding practice was not frequent in both groups. The average energy intake and weight gain were similar in the 2 groups. This study demonstrated that nucleotide supplementation of infant formula during episodes of acute diarrhea has no therapeutic advantage compared to conventional infant formula.
Amino Acid Synthesis and Metabolism
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