Adenine, The Precursor of Nucleic Acids in Intestinal Cells Unable to Synthesize Purines De Novo

Abstract

The capacity of rat intestinal epithelial cells for de novo purine synthesis and reutilization was studied in vitro with isolated cells and in vivo in functionally hepatectomized rats. De novo purine synthesis and purine reutilization were measured as the rate of incorporation of [14C]-glycine or [14C]-adenine, respectively, into the adenine and guanine pools of the intestinal cells. Isolated intestinal epithelial cells incubated with labeled purine or glycine incorporated only labeled adenine. Labeled glycine, guanine, hypoxanthine or xanthine were not incorporated into cellular adenine or guanine. Labeled glycine, given intravenously to functionally hepatectomized rats, was not incorporated into the adenine and guanine of intestinal villus or crypt cells. Labeled glycine was readily incorporated into hepatic adenine and guanine pools of a sham-operated rat. The failure of glycine to be incorporated into intestinal cells in vitro or in vivo demonstrated that these cells lack de novo purine synthesis. Since adenine was readily incorporated into the adenine pool of these cells, we believe that adenine, which is synthesized in the liver or supplied in the diet, was an important precursor for the nucleic acid synthesis in this study.

The role of dietary nucleotides in single-stomached animals

“…In the absence of dietary nucleotides, the de novo pathway for purine and pyrimidine synthesis is activated (26) . However, supplementing nucleotides may suppress the metabolic costly de novo synthesis, thereby activating the salvage pathway (24,25,45) . Thus, the term 'semi-essential nutrient' has been introduced to describe the role of dietary nucleotides in nutrition of newborn, adult or ill mammals when endogenous supply is insufficient for normal body function, even though their absence from the diet does not necessarily lead to classical clinical aetiopathology (46) .…”

Adenosine: An immune modulator of inflammatory bowel diseases

“…These tissues and cells rely largely on exogenous nucleoside supply and salvage of endogenous nucleobases and nucleosides. Bone marrow, lymphocytes, leukocytes and intestinal epithelial cells are among them [35][36][37][38][39] . The liver is the major organ supplying the nucleobases to these tissue and cells.…”

A regulatory element is characterized by purine-mediated and cell-type-specific gene transcription.

“…Basal expression of the HPRT enzyme appears to be ubiquitous throughout most tissue and cell types (28), but the levels of HPRT mRNA are expressed to some degree in a tissue-specific manner (35); more recently, HPRT mRNA levels have been demonstrated to be affected by the presence of dietary purines and nucleotides in the rat intestine (27). The requirements for normal physiological levels of purines are satisfied by the de novo pathway for purine synthesis in most cell types and tissues (15), but certain cell types exhibit the absence or reduction in de novo purine synthesis, particularly in the intestine (8,26,29,45), bone marrow (25,46), and leukocytes (54). The uptake of purines and nucleotides is much higher in mouse small intestine than in other tissue types (49), consistent with a possible requirement for exogenous purines and nucleotides for active crypt cell proliferation in mature intestinal mucosa.…”