scholarly journals The conversion of orotic acid into uridine 5′-monophosphate by isolated perfused normal and regenerating rat livers

1972 ◽  
Vol 129 (4) ◽  
pp. 811-820 ◽  
Author(s):  
Nelson Fausto

The release of 14CO2 from [7-14C]orotic acid was measured in isolated perfused normal and regenerating rat livers. With some limitations, the release of 14CO2 from [7-14C]orotic acid can be used to estimate UMP synthesis in perfused livers. Isolated perfused livers rapidly pick up labelled orotic acid added to perfusate and convert most of it into UMP. Perfused regenerating livers produce approx. 2.5 times as much UMP/g of liver as do perfused normal livers. However, the absolute amount of orotic acid converted into UMP is higher in perfused normal livers than in perfused regenerating livers. Perfused regenerating livers do not differ in their orotic acid uptake and UMP synthesis from livers of comparable size in which regeneration is not taking place. The total amount of orotic acid taken up by the liver (rather than the rate of uptake) and the size of the liver appear to be the determining factors in UMP production. The results suggest that the decrease in liver size caused by partial hepatectomy may be in itself sufficient to account for an increase in the flow of metabolites in the pyrimidine pathway at the early stages of liver regeneration.

1957 ◽  
Vol 40 (3) ◽  
pp. 451-490 ◽  
Author(s):  
V. G. Allfrey ◽  
A. E. Mirsky ◽  
Syozo Osawa

1. Nuclei prepared from calf thymus tissue in a sucrose medium actively incorporate labelled amino acids into their proteins. This is an aerobic process which is dependent on nuclear oxidative phosphorylation. 2. Evidence is presented to show that the uptake of amino acids represents nuclear protein synthesis. 3. The deoxyribonucleic acid of the nucleus plays a role in amino acid incorporation. Protein synthesis virtually ceases when the DNA is removed from the nucleus, and uptake resumes when the DNA is restored. 4. In the essential mechanism of amino acid incorporation, the role of the DNA can be filled by denatured or partially degraded DNA, by DNAs from other tissues, and even by RNA. Purine and pyrimidine bases, monoribonucleotides, and certain dinucleotides are unable to substitute for DNA in this system. 5. When the proteins of the nucleus are fractionated and classified according to their specific activities, one finds the histones to be relatively inert. The protein fraction most closely associated with the DNA has a very high activity. A readily extractable ribonucleoprotein complex is also extremely active, and it is tempting to speculate that this may be an intermediary in nucleocytoplasmic interaction. 6. The isolated nucleus can incorporate glycine into nucleic acid purines, and orotic acid into the pyrimidines of its RNA. Orotic acid uptake into nuclear RNA requires the presence of the DNA. 7. The synthesis of ribonucleic acid can be inhibited at any time by a benzimidazole riboside (DRB) (which also retards influenza virus multiplication (11)). 8. The incorporation of amino acids into nuclear proteins seems to require a preliminary activation of the nucleus. This can be inhibited by the same benzimidazole derivative (DRB) which interferes with RNA synthesis, provided that the inhibitor is present at the outset of the incubation. DRB added 30 minutes later has no effect on nuclear protein synthesis. These results suggest that the activation of the nucleus so that it actively incorporates amino acids into its proteins requires a preliminary synthesis of ribonucleic acid. 9. Together with earlier observations (27, 28) on the incorporation of amino acids by cytoplasmic particulates, these results show that protein synthesis can occur in both nucleus and cytoplasm.


1993 ◽  
Vol 14 (6) ◽  
pp. 1095-1099 ◽  
Author(s):  
R.K. Sharma ◽  
R.M. Pascale ◽  
S. Narasimhan ◽  
S. Rajalakshmi

Author(s):  
Snobar Gul ◽  
Mohammad Saleem Itoo ◽  
Gousia Nisa

Background: A number of disorders are accompanied by altered size of various abdominal organs like liver including infective, infestation, infiltrative, immunological and malignant conditions. Medical imaging has played an important role in helping physicians for taking normal anatomical dimensions and establishing diagnosis. This study was carried out to determine the normal standards of liver size and its relationship with body weight, height and body mass index.Methods: A cross sectional study was done in GMC Srinagar, Jammu and Kashmir, India for a period of 18 months. 300 staff members in the age group of 19 to 55 years took part in this study.Results: The mean craniocaudal length of liver was 13.08±1.04cms. Authors found a significant correlation of liver size with body weight and body mass index.Conclusions: Body weight and BMI are important determining factors for liver size. Nomograms from this study can be beneficial for diagnosing pathological enlargement or reduction of liver in Kashmiri ethnic population.


1990 ◽  
Vol 259 (2) ◽  
pp. G205-G211 ◽  
Author(s):  
S. J. Robins ◽  
J. M. Fasulo ◽  
G. M. Patton

Bile salts are necessary for the secretion of phosphatidylcholines (PCs) in bile and result in the selective secretion of highly hydrophilic molecular species of PC that contain a 16:0 acyl group. To determine the effect of bile salt on the secretion of PCs in lipoproteins, isolated rat livers were perfused with and without taurocholate. The PC composition of very-low-density lipoproteins (VLDL), newly synthesized by the liver, precisely mirrored the composition of PCs in the whole liver and was not changed with the administration of taurocholate. In contrast, both the composition of PCs in high-density lipoproteins (HDL) and the absolute amount of newly synthesized HDL were markedly affected by the administration of taurocholate. With taurocholate the PC content of HDL was increased, HDL was enriched, like bile, in 16:0 molecular species of PC, and the amount of HDL that was recovered in the perfusate was 2.5-fold greater than without taurocholate (P less than 0.001). These findings suggest that VLDL and HDL are differently derived from within the liver, that the PCs of HDL and bile originate from the same hepatic pool or by the same mechanism, and that both the secretion of bile and HDL from the liver are susceptible to regulation by bile salt.


2005 ◽  
Vol 289 (1) ◽  
pp. G88-G94 ◽  
Author(s):  
Christian Rust ◽  
Kris Bauchmuller ◽  
Peter Fickert ◽  
Andrea Fuchsbichler ◽  
Ulrich Beuers

Taurochenodeoxycholic acid (TCDCA), but not glycochenodeoxycholic acid (GCDCA), activates a phosphatidylinositol 3-kinase (PI3-K)-mediated survival pathway in vitro. Here, the effects of PI3-K inhibition on TCDCA- and GCDCA-induced hepatocellular injury, apoptosis, and bile secretion were examined in the intact liver. In isolated perfused rat livers, bile flow was determined gravimetrically. Hepatovenous lactate dehydrogenase and alanine aminotransferase efflux as markers of liver integrity and biliary secretion of 2,4-dinitrophenyl- S-glutathione (DNP-GS) were determined photometrically. Apoptosis was assessed by immunohistochemistry of active caspase-3 and cytokeratin 18 in liver tissue. Phosphorylation of protein kinase B (PKB/Akt) as a readout of PI3-K activity was determined by immunoblot analysis. Bile acid concentrations were determined by gas chromatography. TCDCA (25 μM) induced moderate liver injury by hepatocellular apoptosis and distinctly reduced bile flow and DNP-GS secretion. In contrast, GCDCA (25 μM) induced severe liver injury by extensive hepatocyte apoptosis. TCDCA strongly activated PI3-K, whereas GCDCA did not markedly affect PI3-K activity. Inhibition of PI3-K by 100 nM wortmannin enhanced TCDCA-induced liver injury and apoptosis and tended to aggravate the cholestatic effect of TCDCA. In contrast, wortmannin reduced GCDCA-induced liver injury and apoptosis. Bile acid uptake tended to be reduced by wortmannin. The cholestatic effect of GCDCA was aggravated by wortmannin. Inhibition of PI3-K markedly aggravated TCDCA-induced but not GCDCA-induced liver damage and hepatocyte apoptosis. Thus TCDCA appears to block its inherent toxicity by a PI3-K-dependent survival pathway in the intact liver.


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