Purine synthesis de novo and its regulation in rat hepatocytes

1980 ◽  
Vol 58 (8) ◽  
pp. 599-606 ◽  
Author(s):  
Christine Des Rosiers ◽  
Marcel Lalanne ◽  
Joan Willemot
Keyword(s):  
Pentose Phosphate Pathway ◽  
De Novo ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Pentose Phosphate ◽  
Male Rats ◽  
P Availability ◽  
Prolonged Incubation ◽  
Purine Synthesis ◽  
Stimulation Of

Purine synthesis de novo and its regulation were studied in freshly isolated hepatocytes from fed adult male rats. These cells incorporated [14C]formate mainly into purine ribonucleotides. The immediate effect of increasing the concentration of inorganic phosphate in the incubation medium was an increase in 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P) availability and a stimulation of purine synthesis de novo. However, prolonged incubation of cells in 25 mM phosphate resulted in a decreased PP-ribose-P availability and purine synthesis de novo. Methylene blue and phenazine methosulfate decreased PP-ribose-P availability and purine synthesis de novo although they stimulated considerably the pentose phosphate pathway. In contrast, epinephrine and glucagon increased significantly PP-ribose-P availability and purine synthesis de novo, but they did not change the activity of the pentose phosphate pathway. These results show a relationship between PP-ribose-P availability and purine synthesis de novo in rat hepatocytes. They emphasize the complexity of the regulation of PP-ribose-P availability.

scholarly journals AMINO ACIDS REGULATE DE NOVO PURINE SYNTHESIS VIA AKT REGULATION OF PENTOSE PHOSPHATE PATHWAY ENZYMES

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Arindam Saha ◽  
Deron Amador ◽  
Alla Fridman ◽  
Renate Pilz ◽  
Gerry Boss
Keyword(s):  
Amino Acids ◽  
Pentose Phosphate Pathway ◽  
De Novo ◽  
Pentose Phosphate ◽  
Purine Synthesis

The effects of acetate and of pyruvate on the pathways of glucose catabolism in lactating mammary tissue. II. Sheep tissue

1969 ◽  
Vol 36 (3) ◽  
pp. 469-478 ◽  
Author(s):  
R. W. Smith ◽  
R. F. Glascock
Keyword(s):  
Pentose Phosphate Pathway ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Mammary Tissue ◽  
Glucose Catabolism ◽  
Glucose Carbon ◽  
Rat Tissue ◽  
The Relationship ◽  
Stimulation Of

SummaryA study was made of the changes in the rates of oxidation of the C(1), C(2) and C(6) atoms of glucose and in the pathways of glucose catabolism in sheep udder tissue in vitro which occurred when acetate and pyruvate were added.Whereas in rat mammary tissue the rate of oxidation of the C(1) atom of glucose was very much greater than that of the C(6) atom, the ratio of the rates of oxidation of these 2 atoms in sheep tissue was less than 2 when glucose was the only substrate.The addition of acetate resulted in an unequal stimulation of the oxidation of these 2 atoms, with the result that the ratio of their rates of oxidation was about doubled. The rate of oxidation of the C(2) atom was also increased.Acetate also increased the participation of the pentose phosphate pathway in glucose catabolism as measured by the incorporation of the C(1) and C(6) atoms of glucose into fatty acids, lactic acid and glycerol.Pyruvate produced little effect on the rate of oxidation of the C(1) atom but somewhat depressed that of the C(6) atom of glucose. At the same time, it caused a large increase in the participation of the pentose phosphate pathway.These results are discussed with reference to re-cycling of glucose carbon in the pentose phosphate pathway and to the relationship between that pathway and fatty acid synthesis. It is noted that the incorporation of glucose carbon into the 3 intermediates used gave values for the participation of that pathway which were in better agreement than was obtained in rat tissue. It is concluded that triose phosphates are more nearly in equilibrium in sheep than in rat mammary tissue.

scholarly journals The Pentose Phosphate Pathway and Pyruvate Carboxylation after Neonatal Hypoxic-Ischemic Brain Injury

2014 ◽  
Vol 34 (4) ◽  
pp. 724-734 ◽  
Author(s):  
Eva MF Brekke ◽  
Tora S Morken ◽  
Marius Widerøe ◽  
Asta K Håberg ◽  
Ann-Mari Brubakk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
De Novo ◽  
Pentose Phosphate ◽  
Adult Brain ◽  
Resonance Spectroscopy ◽  
Neonatal Brain ◽  
Artery Ligation ◽  
Pyruvate Carboxylation

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-13C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using 1H- and 13C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.

scholarly journals The effects of added purines on urate and purine synthesis de novo by isolated chick liver, kidney and lymphoid cells

1976 ◽  
Vol 158 (3) ◽  
pp. 549-556 ◽  
Author(s):  
P Badenoch-Jones ◽  
P J Buttery
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Liver Cells ◽  
Lymphoid Cells ◽  
Kidney Cells ◽  
Purine Synthesis ◽  
Liver And Kidney ◽  
Stimulation Of

1. Isolated chick lymphoid cells, together with isolated chick liver and kidney cells, incorporate [1-14C]glycine or [14C]formate into urate. 2. Of the cell types used, bursal cells incorporate 14C into urate at the fastest rate, although the output of total urate by bursal cells is only 10% that of liver cells. 3. When suspended in Eagle's medium the incorporation of 14C into urate is inhibited by adenine and guanine up to 1 mM. In contrast, the addition of 1 mM-AMP or -GMP results in a relatively large stimulation of this incorporation. 4. Added adenine is rapidly taken up by liver cells and then released in an unmetabolized form; AMP is taken up more slowly and is rapidly metabolized. The metabolites (possibly including adenine) are then released. 5. Intracellular liver 5-phosphoribosyl 1-pyrophosphate is approx. 0.7mM and remains constant or falls slightly during a 3 h incubation of the cells. 6. The addition of adenine or guanine, AMP or GMP, does not alter liver intracellular 5-phosphoribosyl 1-pyrophosphate concentrations. Added 5-phosphoribosyl 1-pyrophosphate is not taken up by liver cells. 7. The results are discussed in the context of the control of urate and purine synthesis de novo in the chick.

scholarly journals Prostaglandins E2 and F2α increase fructose 2,6-bisphosphate levels in isolated hepatocytes

1991 ◽  
Vol 274 (1) ◽  
pp. 309-312 ◽  
Author(s):  
A M Gómez-Foix ◽  
J E Rodríguez-Gil ◽  
J J Guinovart ◽  
F Bosch
Keyword(s):  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Glycolytic Flux ◽  
Dependent Manner ◽  
Hepatic Glucose Metabolism ◽  
Prostaglandin F2 Alpha ◽  
Hepatic Glucose ◽  
Dose Dependent ◽  
Prostaglandins E2 And F2α ◽  
Stimulation Of

In hepatocytes isolated from fed rats, prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) increased, in a time- and dose-dependent manner, fructose 2,6-bisphosphate [Fru(2,6)P2] levels and stimulated the glycolytic flux. The rise in Fru(2,6)P2 was related to an increase in glucose 6-phosphate levels which resulted from the stimulation of glycogenolysis. In cells obtained from 24 h-starved rats, no effects of either PGE2 or PGF2 alpha could be observed. In addition, when the stimulation of glycogenolysis was abolished by incubation of fed-rat hepatocytes in a Ca2(+)-depleted medium, Fru(2,6)P2 levels did not increase. Furthermore, no effects of PGs on 6-phosphofructo-2-kinase activity could be observed. These results indicate that PGE2 and PGF2 alpha show similar actions to Ca2(+)-dependent hormones on hepatic glucose metabolism.

Increased de novo purine synthesis by insulin through selective enzyme induction in primary cultured rat hepatocytes

1990 ◽  
Vol 258 (5) ◽  
pp. C841-C848 ◽  
Author(s):  
M. Tsuchiya ◽  
H. Yoshikawa ◽  
M. Itakura ◽  
K. Yamashita
Keyword(s):  
Enzyme Induction ◽  
De Novo ◽  
Feedback Inhibition ◽  
Rat Hepatocytes ◽  
Purine Metabolism ◽  
Hepatocyte Proliferation ◽  
Adenylate Energy Charge ◽  
Purine Synthesis ◽  
Primary Cultured Rat Hepatocytes ◽  
Cultured Rat Hepatocytes

The proliferative effect of insulin on de novo purine synthesis and on the expression of various enzymes of purine metabolism were studied in primary cultured rat hepatocytes. Insulin greater than 1.5 x 10(-8) M increased DNA and de novo purine synthesis to 260-390 and 270-420%, respectively, 24 and 8 h after the administration. Insulin at 1.5 x 10(-7) M increased the specific activity of amidophosphoribosyltransferase (ATase) to 154-180%, hypoxanthine-guanine phosphoribosyltransferase to 129%, and adenine phosphoribosyltransferase (APRT) to 205%, in contrast to unchanged xanthine dehydrogenase at 80%. Enzyme induction was supported by the results of kinetic analysis and the inhibition of the insulin-induced increase in enzyme activities by protein synthesis inhibitors. Insulin increased ATP to 127% and decreased AMP, ADP, 5'-guanylic acid (GMP), and guanosine 5'-diphosphate (GDP), respectively, to 73, 69, 73, and 69%. Insulin increased adenylate energy charge from 0.83 to 0.90 without changing total feedback inhibitory potential on ATase. No obvious increase of 5-phosphoribosyl-1-pyrophosphate supply was suggested, although its apparent availability for purine ribonucleotide synthesis was increased to 208-245%, reflecting mainly induced APRT activity to 205%. It is concluded that hepatocyte proliferation by insulin, as evidenced by purine metabolism, is mediated by the selective gene activation of anabolic enzymes and increased ATP as the basis to activate multiple metabolic pathways without remarkable changes of substrate availability or feedback inhibition.

The effect of serum from obese and normal weight men on glucose metabolism in leucocytes

1980 ◽  
Vol 95 (1) ◽  
pp. 134-138 ◽  
Author(s):  
Ole Myking ◽  
Berit Kjøsen ◽  
Hans H. Bassøe
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
Lactate Production ◽  
Normal Weight ◽  
Pentose Phosphate ◽  
Obese Group ◽  
Stimulation Of

Abstract. The influence of pooled serum from either obese or normal weight males on glucose metabolism in human leucocytes has been studied. Leucocytes from normal weight males were incubated with 10–90% pooled serum and either [U-14C], or [1-14C]glucose. Compared to serum from the normal weight males, serum from the obese group had a more stimulating effect on the 14CO2 and [14C]lactate production from [U-14C]glucose and on the 14CO2 production from [1-14C]glucose. The two serum pools had the same stimulating effect on the Embden-Meyerhof pathway as indicated by the formation of [14C]lactate from [1-14C]glucose. Calculations revealed that the activity in the pentose phosphate pathway was stimulated more by serum from obese, than from normal weight males. It is a possibility that increased stimulation of the pentose phosphate pathway may contribute to the development of overweight.

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