scholarly journals Potentiation by ammonia of the metabolic effects of pent-4-enoate in isolated rat hepatocytes

1984 ◽  
Vol 224 (1) ◽  
pp. 263-267 ◽  
Author(s):  
F X Coudé ◽  
G Grimber ◽  
P Parvy ◽  
D Rabier ◽  
J Bardet

The metabolic effects of pent-4-enoate were studied in isolated rat hepatocytes; 1 mM-pent-4-enoate did not significantly inhibit gluconeogenesis from lactate, alanine and glycerol, but significantly decreased glucose synthesis from pyruvate. The addition of 1 mM-NH4Cl led to a drastic inhibition of glucose synthesis from all these substrates. In hepatocytes incubated with 10 mM-alanine and 1 mM-oleate, pent-4-enoate at 0.05-1 mM slightly inhibited glucose synthesis and ketogenesis. The addition of ammonia resulted in a dramatic potentiation of the metabolic effects of pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of ATP and acetyl-CoA were also decreased by the addition of ammonia, as were lactate/pyruvate ratio and beta-hydroxybutyrate/acetoacetate ratio. These data suggest that ammonia seriously interferes with the cellular metabolism of pent-4-enoate and leads to a dramatic potentiation of its effects.

1995 ◽  
Vol 306 (3) ◽  
pp. 693-696 ◽  
Author(s):  
S Claeyssens ◽  
A Francois ◽  
A Chedeville ◽  
A Lavoinne

The effect of microcystin-LR, an inhibitor of protein phosphatases PP1 and PP2A, was studied on protein synthesis by measuring the incorporation of labelled amino acid into protein in isolated rat hepatocytes. Microcystin-LR inhibited protein synthesis in the first minutes of the incubation period, and half-maximum effect was obtained at about 60 nM. Such an inhibition was also observed in the presence of different protein phosphatase inhibitors, i.e. okadaic acid, calyculin A and microcystin-RR. This effect was observed in whole hepatocytes, in the supernatant of the post-mitochondrial fraction and in the microsomal fraction. It was independent of a substrate supply and of the labelled amino acid used. Furthermore, this inhibition preceded the previously reported glucose-6-phosphatase activation induced by microcystin-LR [Claeyssens, Chédeville and Lavoinne (1993) FEBS Lett. 315, 7-10].


1986 ◽  
Vol 70 (6) ◽  
pp. 627-634 ◽  
Author(s):  
Rita A. Klim ◽  
Marta Albajar ◽  
Reginald Hems ◽  
Dermot H. Williamson

1. The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. 2. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. 3. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. 4. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). 5. Livers of uraemic rats had increased activities of glutarninase (30%) and serine dehydratase (100%). 6. Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. 7. The possible implications of these findings for human uraemia are discussed.


1995 ◽  
Vol 69 (2) ◽  
pp. 173-176
Author(s):  
Takahide Nomura ◽  
Masatsugu Ohtsuki ◽  
Toshiko Watanabe ◽  
Seiko Hasegawa ◽  
Shigeru Matsui ◽  
...  

1985 ◽  
Vol 228 (1) ◽  
pp. 277-280 ◽  
Author(s):  
J A García-Sáinz ◽  
F Mendlovic ◽  
M A Martínez-Olmedo

Phorbol 12-myristate 13-acetate (PMA) inhibited the stimulation of ureogenesis produced by adrenaline, but produced a minimal displacement to the right of the dose-response curve for glucagon. However, PMA diminished the accumulation of cyclic AMP induced by glucagon. Dissociation between the cyclic AMP concentrations and the metabolic effects induced by glucagon is evidenced in the presence of phorbol esters.


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