De Novo purine biosynthesis by two pathways in Burkitt lymphoma cells and in human spleen

Reem, Gabifltl F. H.

doi:10.1172/jci106897

Cited by 48 publications

(18 citation statements)

References 8 publications

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“…It is known that PRA is formed by two alternative pathways: one is the reaction of PRA formation from 5-phosphoribosyl-1-pyrophosphate (PRPP) and glutamine or ammonia, and the other is PRA formation from ribose-5-phosphate and ammonia7, 8,9). The rate of PRA synthesis depends on the concentration of precursors mentioned above, as well as on the activity of enzymes involved in the reactions.…”

Section: Resultsmentioning

confidence: 99%

Effect of Ribose and Ribose-5-phosphate on Uric Acid Synthesis in the Chicken

Karasawa

Tasaki

1975

Nihon Chikusan Gakkaiho

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Studies on purine synthesis of red cells and fibroblasts in patients suffering from purine overproduction provided an evidence that purine overproduction associates with an increased 5-phosphoribosyl-1-pyrophosphate formation, which is one of the substrates for phosphoribosyl-1-amine formation in the initial step of purine biosynthesis1). This finding suggests that ribose and ribose-5-phosphate may play an important role in urate synthesis of animals. In order to examine whether or not ribose, ribose-5 phosphate, glucose or fructose has the stimulatory effect on purine biosynthesis in chickens, the present experiment was carried out. ExperimentalFive-month-old single-comb White Leghorn cockerels, weighing about 2kg, were used as the experimental animal. The chickens were fed 35g of an experimental diet per kilogram of body weight once a day (9:00AM) for 5 days. The diet provided was consumed within 40 minutes, and all birds slightly gained body weight. Water was freely available. The experimental diet used in this experiment was a 20% protein diet containing heat-dried egg albumen as the sole source of protein, and the composition of the diet was described in the previous paper2).Cardiac, portal and ureter catheterization was performed in the same manner as described previously2). Heparin (200units/kg) was injected into the circulatory blood through the cardiac catheter as an anticoagulant. The cardiac and ureter catheters were used for the blood and urine collection, respectively. Six hours after feeding on day 5 the test solution was continuously infused into the portal vein through the portal catheter with a speed controlled injector for 60 minutes. Either D-(-)-riboseor D-(-)-ribose-5-phosphate (disodium salt) with either L-glutamine or ammonium acetate was dissolved in a 5% glucose solution as to make 0.0295M of those or ribose-5-phosphate and 0.18M of glutamine or ammonium acetate, and then the test solutions were adjusted to pH7.4. Infusion rates of ribose or ribose-5-phosphate and glutamine or ammonium acrate of 0.556ml per minute and the experimental birds weighed about 2kg. As a control, saline, 5% glucose and 5% fructose solutions were similarly infused.About 3.5ml of cardiac blood was sampled through the cardiac catheter 60 minutes after the commencement of infusion. Total urine was collected through the right and left ureter catheters

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Section: Resultsmentioning

confidence: 99%

Effect of Ribose and Ribose-5-phosphate on Uric Acid Synthesis in the Chicken

Karasawa

Tasaki

1975

Nihon Chikusan Gakkaiho

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“…Nevertheless, suggestive evidence for this pathway exists in other systems (103)(104)(105), and Reeni (65,66) has shown that tissue extract fractions that catalyze this reaction contain no glutamine PP-ribose-P amidotransferase activity. The '5N-9/'5N-3 ratios of the present study could perhaps be explained by a direct reaction between ammonia and ribose 5-P, occurring either enzymatically or chemically, giving rise to phosphoribosylamiine.…”

Section: Methodsmentioning

confidence: 98%

“…The results presented thus far favor a kinetic explanation of the observed enhancement of labeling of N-(3 + 9) in gouty overproducers, which is independent of the nature of the specific metabolic abnormality that initiates purine overproduction.' However, Reem (65) has suggested an 'A computer model has been constructed simulating the kinetics of the reaction sequence of Fig. 8.…”

Section: Methodsmentioning

confidence: 99%

The Kinetics of Intramolecular Distribution of 15N in Uric Acid after Administration of [15N]Glycine A REAPPRAISAL OF THE SIGNIFICANCE OF PREFERENTIAL LABELING OF N-(3 + 9) OF URIC ACID IN PRIMARY GOUT

Sperling¹,

Wyngaarden²,

Starmer³

1973

J. Clin. Invest.

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A B S T R A C T The concept of an abnormality of glutamine metabolism in primary gout was first proposed on the basis of isotope data: when ["N]glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3 + 9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of "N in glutamine was postulated, and attributed to a hypothetical defect in catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction.We have reexamined this proposition in four gouty subjects: one mild overproducer of uric acid with "idiopathic gout," one marked overproducer with high-grade but "partial" hypoxanthine-guanine phosphoribosyltransferase deficiency, and two extraordinary overproducers with superactive phosphoribosylpyrophosphate synthetases. In the last three, the driving force of excessive purine biosynthesis is a known surplus of a-5-phosphoribosyl-l-pyrophosphate. Disproportionately high labeling of N-(3 + 9) was present in all four gouty subjects, most marked in the most flamboyant overproducers. The precursor glycine pool was sampled by periodic administration of benzoic acid and isolation of urinary hippuric acid. Similarly, the precursor glutamine pool was sampled by periodic administration of phenylacetic acid and isolation of the amide-N of urinary phenylacetylglutamine. The ment of hippurate differed from that of the amide-N of glutamine. Whereas initial enrichment values of hippurate were very high, those of glutamine-amide-N were low, increasing to a maximum at about 3 h, and then declining less rapidly than those of hippurate. However, enrichment values of hippurate and of phenacetyl glutamine were normal in all of the gouty subjects studied. Thus, preferential enrichment of N-(3 + 9) in gouty overproducers given ["N]glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic phenomenon associated with accelerated purine biosynthesis per se.In addition, greater enrichment of N-9 than of N-3 on days 1 and 2 provided suggestive evidence for a second pathway for synthesis of the initial precursor of purine biosynthesis, phosphoribosylamine, perhaps utilizing ammonia rather than the amide-N of glutamine as nitrogen donor. In this limited study, the activity of this potential second pathway did not appear to be selectively increased in gout.

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“…Rib-5-P aninotransferase P-RibN + ADP + P, [3] ed that two other enzymatic activities also catalyze the synthesis of P-RibN in eukaryotic cells (2)(3)(4)(5). The first of these (reaction 2) has been called ammonia P-Rib-P-P aminotransferase (PRib-P-P aminotransferase) (3)(4)(5).…”

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confidence: 99%

A Purine Auxotroph Deficient in Phosphoribosylpyrophosphate Amidotransferase and Phosphoribosylpyrophosphate Aminotransferase Activities with Normal Activity of Ribose-5-phosphate Aminotransferase

Ew¹,

Gl²,

Leyva³

et al. 1977

Purine Metabolism in Man—II

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Three enzyme reactions have been reported to catalyze the synthesis of phosphoribosylamine in eukaryotic cells. These activities are glutamine phosphoribosylpyrophosphate (P-Rib-P-F) amidotransferase [amidophosphoribosyl-transferase; 5-phosphoribosylamine: pyrophosphate phosphoribostransferase (glutamate-amidating) EC 2.4±2.141 ammonia P-Rib-P-P aminotransferase, and ammonia ribose5-Iphosphate aminotransferase. A purine auxotroph derived from a cell line of Chinese hamster fibroblasts was shown to be deficient in catalytic activities of glutamine P-Rib-P-P amidotransferase and ammonia P-Rib-P-P aminotransferase. Extracts from this cell line had normal ammonia ribose--phosphate aminotransferase activity. The defect in purine biosynthesis in the mutant cell line was localized to the synthesis of phosphoribosylamine. These results indicate that glutamine P-Rib-P-P amidotransferase or ammonia P-Rib-P-P aminotransferase or both are important for phosphoribosylamine synthesis, but that ammonia ribose-phosphate aminotransferase activity probably does not play a significant role in this eukaryotic cell line. The simultaneous disappearance of both P-Rib-P-Pdependent activities suggests these two enzyme activities are closely related structurally or genetically. The synthesis of phosphoribosylamine (P-RibN) is the first committed reaction unique to purine biosynthesis de novo (1). Traditionally the catalysis of this reaction has been attributed to the enzyme glutamine phosphoribosylpyrophosphate amidotransferase (P-Rib-P-P amidotransferase, reaction 1) [amidophosphoribosyltransferase; EC 2.4.2.14; 5-phosphoribosylamine:pyrophosphate phosphoribosyltransferase (glutamate-amidating)]. However, recent studies have suggestGlutamine + P-Rib-P-P + H20 P-Rib-P-P amidotransferas P a P-RibN + glutamate + PPj [1] NH3 + P-Rib-P-P + H20 P-Rib-P-P amintransferawe, PRibN + PPj [2] Rib-S5-P + ATP + NH3Rib-5-P aninotransferase P-RibN + ADP + P, [3] ed that two other enzymatic activities also catalyze the synthesis of P-RibN in eukaryotic cells (2-5). The first of these (reaction 2) has been called ammonia P-Rib-P-P aminotransferase (PRib-P-P aminotransferase) (3-5). This enzyme utilizes ammonia rather than glutamine as substrate and has been sepaAbbreviations: P-RibN, phosphoribosylamine; P-Rib-P-P amidotransferase, amidophosphoribosyltransferase (EC 2.4.2.14); P-Rib-P-P aminotransferase, ammonia phosphoribosylpyrophosphate aminotransferase; Rib-S5-P aminotransferase, ammonia ribose-5-phosphate aminotransferase; P-Rib-GlyN, phosphoribosylglycinamide. rated from P-Rib-P-P amidotransferase on gel filtration chromatography (4). This activity may represent a distinct protein or a subunit of P-Rib-P-P amidotransferase. A third enzyme, ammonia ribose-5-phosphate aminotransferase (Rib-5-P aminotransferase), has also been reported to catalyze the synthesis of P-RibN (reaction 3) (2-5). However, the determination of P-RibN in this reaction has required an assay coupled with the second enzyme in the purine biosynthetic pathway. Since other...

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De Novo purine biosynthesis by two pathways in Burkitt lymphoma cells and in human spleen

Cited by 48 publications

References 8 publications

Effect of Ribose and Ribose-5-phosphate on Uric Acid Synthesis in the Chicken

Effect of Ribose and Ribose-5-phosphate on Uric Acid Synthesis in the Chicken

The Kinetics of Intramolecular Distribution of 15N in Uric Acid after Administration of [15N]Glycine A REAPPRAISAL OF THE SIGNIFICANCE OF PREFERENTIAL LABELING OF N-(3 + 9) OF URIC ACID IN PRIMARY GOUT

A Purine Auxotroph Deficient in Phosphoribosylpyrophosphate Amidotransferase and Phosphoribosylpyrophosphate Aminotransferase Activities with Normal Activity of Ribose-5-phosphate Aminotransferase

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