Glutamine synthesis in the perfused rat kidney and in isolated rat cortical tubules: regulation by pH

1985 ◽  
Vol 69 (6) ◽  
pp. 701-707 ◽  
Author(s):  
Henri Lanctin ◽  
John T. Brosnan ◽  
Brian D. Ross

1. The possible involvement of renal glutamine synthesis in the regulation of ammoniagenesis during metabolic acidosis has been investigated. 2. Using an isotope dilution technique glutamine synthesis has been demonstrated in the intact perfused rat kidney, despite zero net balance for glutamine in this preparation. 3. Inhibition of glutamine synthesis resulted in increased ammonia production in isolated cortical tubules. The rates of these processes were comparable. 4. We conclude that recycling of nitrogen through glutamine synthesis and glutamine hydrolysis could play a quantitatively significant role in the control of ammonia excretion by the kidney, particularly in acute acidosis where the fall in pH seems to inhibit glutamine synthesis.

1979 ◽  
Vol 57 (1) ◽  
pp. 103-111 ◽  
Author(s):  
B. D. Ross ◽  
R. L. Tannen

1. An isolated perfused rat kidney preparation which responds to acidification of the perfusion medium with the production of an acid urine and increased ammonia production was used to study the metabolic regulation of ammonia production from glutamine. 2. An inhibitor of gluconeogenesis at phosphoenolpyruvate carboxykinase(GTP), mercaptopicolinate, completely prevented the increase in ammoniagenesis, without preventing acidification of the urine. 3. Acidification of the perfusion medium from pH 7·4 to 7·0 reduced the renal concentrations of malate and 2-oxoglutarate. 4. Malate concentration was restored by inhibition of phosphoenolpyruvate carboxykinase(GTP), but 2-oxoglutarate content remained low. This indicates that accelerated gluconeogenesis in acute acidosis cannot be the explanation for the fall in 2-oxoglutarate concentration. 5. The fall in 2-oxoglutarate content is taken to indicate an important fall in tissue pH or in the redox ratio (NAD+/NADH) or both during acute metabolic acidosis. 6. From these studies with lowered bicarbonate two separate stimuli to ammoniagenesis in acute metabolic acidosis are postulated: urinary trapping of ammonia and increased disposal of glutamine carbon atoms via the pathway of glucose synthesis.


1976 ◽  
Vol 31 (9-10) ◽  
pp. 509-513 ◽  
Author(s):  
D Müller-Enoch ◽  
H Thomas ◽  
W Streng ◽  
W Ildfeuer ◽  
O Haferkamp

Abstract In the yeasts C. albicans, C. tropicalis, and C. stellatoidea but not in C. krusei, R. rubra, and S. cerevisiae enzyme activity was found by which - as by the catechol-O-methyltransferase (EC 2.1.1.6) found in the liver - the O-methylation of epinephrine to metanephrine and paranephrine, of 3,4-dihydroxybenzoic acid to 4-hydroxy-3-methoxybenzoic acid and 3-hydroxy-4-methoxybenzoic acid, and of 6,7-dihydroxycoumarin to 7-hydroxy-6-methoxycoumarin and 6-hydroxy-7-methoxy-coumarin is catalysed. When the substrates 3,4-dihydroxybenzoic acid, or 6,7-dihydroxycoumarin or epinephrine were incubated in the presence of S-adenosyl-ʟ-[methyl-14C] methionine and S-adenosylmethionine hydrogensulfate with a 100 000 X g supernatant of C. albicans, C. tropicalis or C. stellatoidea the cor­responding O-methylethers were detected in the extracts of the incubation medium by thin-layer chromatography. Final identification of the isomeric radioactive O-methylethers obtained from 3,4-dihydroxy­ benzoic acid and 6,7-dihydroxycoumarin was performed after thin-layer chromatographic separation by the reversed isotope dilution technique. The radioactive m-and p-O-methyl derivatives from epinephrine were separated by thin-layer chromatography and then cleaved with periodate to the corresponding aldehydes which were also identified mainly by the reversed isotope dilution technique.


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