Fructose and liver protein synthesis.

Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm HgO2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 mm of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm HgO2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm HgO2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis.

FRUCTOSE AND LIVER PROTEIN SYNTHESIS - …

Liver adenine nucleotides: fructose-induced depletion and its effect on protein synthesis

Fructose-Induced Depletion and Its Effect on Protein Synthesis.

Researchers1 have investigated the effects of morning fructose consumption on fatty acid synthesis in 6 healthy subjects. The subjects were fed 85 grams of either glucose, a 50:50 fructose glucose mixture or a 75:25 fructose glucose mixture for breakfast, followed 4 hours later by a normal lunch. As expected serum glucose and insulin levels were highest after consumption of the glucose only meal. Lipogenesis was stimulated by both of the fructose meals and resulted in a 2-fold higher level of absolute lipogenesis (17%) when compared to a glucose only meal (8%). Consumption of the fructose meals resulted in plasma triglycerides that were 11 to 29% higher following the subsequent normal lunch, when compared to glucose. In a similar fashion, there was a 76 to 200% greater concentration of very low density lipoprotein (VLDL) after the normal lunch following a fructose meal, when compared to glucose.

for glucose or glycogen synthesis, ..

AB - Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm HgO2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 mm of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm HgO2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm HgO2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis.

1. Acta Med Scand Suppl. 1972;542:115-8. Fructose and liver protein synthesis. Mäenpää PH. PMID: 4516485 [PubMed - indexed for MEDLINE] MeSH Terms

Protein Synthesis Overview; Amino Acids; ..

and then glycerol 3-phosphate for TG synthesis

Pentose Phosphate Pathway, Fructose and Galactose Metabolism