Feedback Control of Purine Biosynthesis by Purine Ribonucleotides

Wyngaarden, James Β.; Ashton, Doris M.

doi:10.1038/183747a0

Cited by 37 publications

(36 citation statements)

References 11 publications

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“…In the biosynthesis of purine nucleotides, WYNGAARDEN et al (16) found that 5-phosphoribosylpyrophosphate (PRPP)-amidotransf erase of pigeon liver was inhibited by several purine nucleotides and MAGASANIK et al (10) reported that formations of inosinicase and IMP-dehydrogenase in S, typhimurium and A. aerogenes were repressed by guanine. The results presented in this paper indicate that in B. subtilis, too, the formations of IMP-transformylase and IMP-dehydrogenase are repressed by various purine derivatives, and the de novo synthesis of purine nucleotides is inhibited by GMP derivatives.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Biochemical Studies on 5′-Nucleotide Fermentation

Momose¹,

NISHIKAWA²,

Katsuya³

1965

J. Gen. Appl. Microbiol.

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Section: Discussionmentioning

confidence: 99%

Genetic and Biochemical Studies on 5′-Nucleotide Fermentation

Momose¹,

NISHIKAWA²,

Katsuya³

1965

J. Gen. Appl. Microbiol.

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“…Purine synthesis is depressed by purine feeding in the rat (34,35). Wyngaarden, Silberman, Sadler and Ashton, using pigeon liver, have extensively studied the in vitro effects of purine derivatives on the reactions involved in their synthesis (36)(37)(38). While the site at which the normal control of purine synthesis occurs has not been established, several purine nucleotides have been shown to inhibit the enzymes involved in early steps of this process, and a specific feedback mechanism similar to that in bacteria has therefore been postulated to explain these observations.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Site of the Feedback Control of Cholesterol Synthesis*†

Siperstein¹,

Guest²

1960

J. Clin. Invest.

259

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“…The subsequent synthesis of urate and its excretion has two major physiological advantages. It In non-uricotelic organisms, when purine synthesis serves only to supply purine nucleotides, synthesis is regulated mainly through feedback inhibition of phosphoribosyl pyrophosphate amidotransferase (EC 2.4.2.14) by adenine and guanine nucleotides (Wyngaarden & Ashton, 1959). Thus, when enough adenine and guanine nucleotides are present further synthesis of purine ceases.…”

Section: Effect Of Nh4cimentioning

confidence: 99%

Rate-limiting factors in urate synthesis and gluconeogenesis in avian liver

Mapes

Krebs

1978

Biochemical Journal

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1. Urate synthesis and other metabolic characteristics of isolated chicken hepatocytes were studied. 2. The distinction is made between immediate precursors of the purine ring (glycine, glutamine, aspartate, formyltetrahydrofolate, bicarbonate) and ultimate precursors from which the immediate precursors are formed in the liver. 3. In hepatocytes from well-fed chickens the rate of urate synthesis was not greatly increased by the addition of amino acids or NH4CI, but in hepatocytes from 72 h-starved chickens the rate was much increased when alanine or asparagine was added as the only substrate. Other amino acids, when added alone, did not affect the rate. The exceptional effect of alanine and asparagine is due to the ready formation of the immediate precursors. 4. Conditions are described under which glutamine, serine, glycine plus formate, ribose and glucose increased the rate of urate synthesis. 5. At I mM-NH4Cl (a concentration not much higher than that of blood plasma) the rate of urate synthesis in the presence of lactate was increased, but higher concentrations inhibited urate synthesis in the presence of lactate or alanine; with alanine even 1 mM-NH4Cl was inhibitory. 6. Gludose synthesis from lactate, alanine or dihydroxyacetone was also inhibited by I mM-NH4CI. 7. NH4Cl inhibition of urate and glucose synthesis was paralleled by an increased rate of glutamine synthesis.Thus in the presence of NH4CI the gluconeogenic precursors are diverted from the pathway of gluconeogenesis to that of glutamate and glutamine synthesis. This implies that the synthesis of these amino acids is the primary process in the detoxication of ammonia in the avian liver. 8. Urate synthesis, like urea synthesis, can be looked on as a cyclic process with either phosphoribosyl pyrophosphate or ribose acting as the carrier on which the purine ring is assembled. 9. The energy requirements of urate synthesis depend on whether phosphoribosyl pyrophosphate is regenerated from IMP by pyrophosphorylase or by phosphorylation and pyrophosphorylation of ribose. It is 6 or 9 pyrophosphate bonds of ATP respectively.The starting point of this work was the intention to use isolated hepatocytes from chicken liver for the study of the rate-limiting factor in uric acid (i.e. purine ring) synthesis. The immediate precursors, as well as the ultimate precursors, of the purine ring are known (see Tables 1 and 2), but information on the factors that determine the rate of the purine-ring synthesis in the intact cell is limited. Barratt et al. (1974) found in the perfused chicken liver that the synthesis of uric acid was only marginally stimulated by the addition of the immediate precursors, i.e. glycine, glutamine, aspartate or NH4CL. In the present experiments on isolated hepatocytes the addition of the immediate precursors listed in Table 1 gave substantial increases in the rates of uric acid synthesis. Unexpectedly, the addition of NH4C1 above I mm strongly inhibited purine-ring synthesis * Present address: Texas A and

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Feedback Control of Purine Biosynthesis by Purine Ribonucleotides

Cited by 37 publications

References 11 publications

Genetic and Biochemical Studies on 5′-Nucleotide Fermentation

Genetic and Biochemical Studies on 5′-Nucleotide Fermentation

Studies on the Site of the Feedback Control of Cholesterol Synthesis*†

Rate-limiting factors in urate synthesis and gluconeogenesis in avian liver

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