scholarly journals Hepatic zonation of the catabolism of arginine and ornithine in the perfused rat liver

1998 ◽  
Vol 330 (2) ◽  
pp. 627-632 ◽  
Author(s):  
Dan O'SULLIVAN ◽  
T. John BROSNAN ◽  
E. Margaret BROSNAN

The metabolism of 14C-labelled arginine and ornithine was studied in the isolated, nonrecirculating, perfused rat liver. The catabolism of these amino acids required ornithine aminotransferase since treatment of rats with gabaculine, an inhibitor of this enzyme, decreased substantially the production of 14CO2 from the 14C-labelled amino acids. In the liver, ornithine aminotransferase is restricted to a small population of hepatocytes proximal to the terminal hepatic vein [Kuo, F. C., Hwu, W. L., Valle, D. and Darnell Jr., J. E. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9468-9472], i.e. the perivenous subpopulation of hepatocytes. Catabolism of arginine requires arginase to convert arginine to ornithine which can then be catabolized through ornithine aminotransferase. The presence of arginase activity in the perivenous hepatocytes was demonstrated by experiments in which livers were perfused with [14C]arginine in both antegrade and retrograde directions. Identical rates of 14CO2 production were obtained in these experiments, a result which could only occur if the process of arginine catabolism through ornithine aminotransferase can be carried out in its entirety in the perivenous cells.

2000 ◽  
Vol 278 (3) ◽  
pp. E516-E521 ◽  
Author(s):  
Dan O'Sullivan ◽  
John T. Brosnan ◽  
Margaret E. Brosnan

The rates of oxidation of arginine and ornithine that occurred through a reaction pathway involving the enzyme ornithine aminotransferase (EC 2.6.1.13 ) were determined using14C-labeled amino acids in the isolated nonrecirculating perfused rat liver. At physiological concentrations of these amino acids, their catabolism is subject to chronic regulation by the level of protein consumed in the diet. 14CO2production from [U-14C]ornithine (0.1 mM) and from [U-14C]arginine (0.2 mM) was increased about fourfold in livers from rats fed 60% casein diets for 3–4 days. The catabolism of arginine in the perfused rat liver, but not that of ornithine, is subject to acute regulation by glucagon (10− 7 M), which stimulated arginine catabolism by ∼40%. Dibutyryl cAMP (0.1 mM) activated arginine catabolism to a similar extent. In retrograde perfusions, glucagon caused a twofold increase in the rate of arginine catabolism, suggesting an effect of glucagon on arginase in the perivenous cells.


1973 ◽  
Vol 134 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Hans A. Krebs ◽  
Reginald Hems ◽  
Patricia Lund

1. The rate of gluconeogenesis from alanine in the perfused rat liver is affected by the presence of other metabolizable substances, especially fatty acids, ornithine and ethanol. Gluconeogenesis is accelerated by oleate and by ornithine. When both oleate and ornithine were present the acceleration was greater than expected on the basis of mere additive effects. 2. Much NH3 and some urea were formed from alanine when no ornithine was added. With ornithine almost all the nitrogen released from alanine appeared as urea. 3. Lactate was a major product of alanine metabolism. Addition of oleate, and especially of oleate plus ornithine, decreased lactate formation. 4. Ethanol had no major effect on gluconeogenesis from alanine when this was the sole added precursor. Gluconeogenesis was strongly inhibited (87%) when oleate was also added, but ethanol greatly accelerated gluconeogenesis when ornithine was added together with alanine. 5. In the absence of ethanol the alanine carbon and alanine nitrogen removed were essentially recovered in the form of glucose, lactate, pyruvate, NH3 and urea. 6. In the presence of ethanol the balance of both alanine carbon and alanine nitrogen showed substantial deficits. These deficits were largely accounted for by the formation of aspartate and glutamine, the formation of which was increased two- to three-fold. 7. When alanine was replaced by lactate plus NH4Cl, ethanol also caused a major accumulation of amino acids, especially of aspartate and alanine. 8. Earlier apparently discrepant results on the effects of ethanol on gluconeogenesis from alanine are explained by the fact that under well defined conditions ethanol can inhibit, or accelerate, or be without major effect on the rate of gluconeogenesis. 9. It is pointed out that in the synthesis of urea through the ornithine cycle half of the nitrogen must be supplied in the form of asparate and half in the form of carbamoyl phosphate. The accumulation of aspartate and other amino acids suggests that ethanol interferes with the control mechanisms which regulate the stoicheiometric formation of aspartate and carbamoyl phosphate.


1976 ◽  
Vol 20 (6) ◽  
pp. 404-414 ◽  
Author(s):  
D.A. Hems ◽  
M.G. Davies ◽  
A.J. Thomas ◽  
P.D. Whitton

1982 ◽  
Vol 201 (1) ◽  
pp. 221-225 ◽  
Author(s):  
J A Williams ◽  
G Bridge ◽  
L J Fowler ◽  
R A John

Rat liver ornithine aminotransferase is found to exchange the pro-S hydrogen on the delta-carbon atom of ornithine exclusively, thus showing that the mammalian enzyme transfers the delta-amino group and not the alpha-amino group as has been demonstrated with the plant enzyme [Mestichelli, Gupta & Spenser (1979) J. Biol. Chem. 254, 640-647]. The enzyme also transfers the alpha-amino group of glutamate and the kinetics of the half reactions between the enzyme and both amino acids are compared. Rate and dissociation constants for both reactions are determined.


1990 ◽  
Vol 371 (1) ◽  
pp. 493-502 ◽  
Author(s):  
Matthias WETTSTEIN ◽  
Stephan VOM DAHL ◽  
Florian LANG ◽  
Wolfgang GEROK ◽  
Dieter HÄUSSINGER

1973 ◽  
Vol 54 (1) ◽  
pp. 89-95 ◽  
Author(s):  
G.E. Mortimore ◽  
A.N. Neely ◽  
J.R. Cox ◽  
R.A. Guinivan

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