Effects of added adenine nucleotides on renal carbohydrate metabolism

Abstract

1. The regulatory effects that adenine nucleotides are known to exert on enzymes of glycolysis and gluconeogenesis were demonstrated to operate in kidney-cortex slices and in the isolated perfused rat kidney by the addition of exogenous ATP, ADP and AMP to the incubation or perfusion media. 2. Both preparations rapidly converted added ATP into ADP and AMP, and ADP into AMP; added AMP was rapidly dephosphorylated. AMP formed from ATP was dephosphorylated at a lower rate than was added AMP, especially when the initial ATP concentration was high (10mM). Deamination ofadded AMP occurred more slowly than dephosphorylation of AMP. 3. Gluconeogenesis from lactate or propionate by rat kidney-cortex slices, and from lactate by the isolated perfused rat kidney, was inhibited by the addition of adenine nucleotides to the incubation or perfusion media. In contrast, oxygen consumption and the utilization of propionate or lactate by slices were not significantly affected by added ATP or AMP. 4. The extent and rapidity of onset of the inhibition of renal gluconeogenesis were proportional to the AMP concentration in the medium and the tissue, and were not due to the production of acid or Pi or the formation of complexes with Mg2+ ions. 5. Glucose uptake by kidney-cortex slices was stimulated 30-50% by added ATP, but the extra glucose removed was not oxidized to carbon dioxide and did not all appear as lactate. Glucose uptake, but not lactate production, by the isolated perfused kidney was also stimulated by the addition of ATP or AMP. 6. In the presence of either glucose or lactate, ATP and AMP greatly increased the concentrations of C3 phosphorylated intermediates and fructose 1,6-diphosphate in the kidney. There was a simultaneous rise in the concentration of malate and fall in the concentration of a-oxoglutarate. 7. The effects of added adenine nucleotides on renal carbohydrate metabolism seem to be mainly due to an increased concentration of intracellular AMP, which inhibits fructose diphosphatase and deinhibits phosphofructokinase. This conclusion is supported by the accumulation of intermediates of the glycolytic pathway between fructose diphosphate and pyruvate. 8. ATP or ADP (10mM) added to the medium perfusing an isolated rat kidney temporarily increased the renal vascular resistance, greatly diminishing the flow rate of perfusion medium for a period of several minutes.

Properties of an Ecto-5’-Nucleotidase of the Renal Brush Border

“…Cata bolism of exogenous nucleotides in the kid ney has been demonstrated in the intact rat as well as in the isolated perfused kidney [4. 32], In the isolated organ the main pathway for degradation of 5'-AMP added to the perfu sate is through 5'-nucleotidase [32], We did not find any informations on the levels of adenine nucleotides in blood plasma. They are probably very low normally, but might increase when tissue is damaged (hemolysis, rhabdomyolysis.…”

The Warburg effect: Evolving interpretations of an established concept

“…Uptake of ATP by animal cells has been speculated [85–88] but has not been experimentally demonstrated. While interstitial ATP concentrations in normal tissues are maintained between 1–1000 nM depending upon tissue type [89–94], intratumoral ATP levels are in the range of several hundred M [95–98], which suggests ATP is readily available for use by hypoxic cancer cells.…”

The Influence of Exogenous ATP on Cardiac Metabolism in Acute Hypoxia

“…This fully corresponds with the con clusions of Krause et al [8], F edeleSova et al [1] and H attori et al [6] to the effect that exogenous ATP, even if it does penetrate, is dephosphorylated near the cell membrane and part of the generated ADP, and especially AMP, becomes rephosphorylated in side the myocardial cell. A further piece of circumstantial evi dence in support of the above-said was offered by Weidemann et al [14] using as a model isolated, perfused, and hypoxic rat kidneys. According to their findings exogenous ATP actually penetrates into the kidney cells and becomes rapidly de phosphorylated and again rephosphorylated inside the cell, near the cell mem brane.…”

“…According to their findings exogenous ATP actually penetrates into the kidney cells and becomes rapidly de phosphorylated and again rephosphorylated inside the cell, near the cell mem brane. Intracellular ATP action could be enhanced through inhibition of 5'-nucleotidase and adenylate deaminase activities by Pj liberated from the ATP break ing down, and the activity of 5'-nucleotidase by ATP as well [14]. By lowering pH of the solution applied with ATP also increases the inhibition of membrane ATPase and the activities of unspecific ATP splitting enzymes.…”