Gamma glutamyltransferase contribution to renal ammoniagenesis in vivo

Welbourne, T. C.; Dass, P. D.

doi:10.1007/bf00582380

Cited by 22 publications

(19 citation statements)

References 42 publications

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“…Rats were killed by an overdose ofthe anesthetic. The resulting arterial para-aminohippuric acid concentrations (< 70 MM) are not likely to influence renal ammoniagenesis ( 15). Also, our urine data in control rats are comparable to studies in which no para-aminohippuric acid was used ( 15,16), providing evidence for the reliability of this urine sampling method.…”

Section: Methodssupporting

confidence: 74%

Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

Dejong¹,

Deutz²,

Soeters³

1993

J. Clin. Invest.

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Section: Methodssupporting

confidence: 74%

Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

Dejong¹,

Deutz²,

Soeters³

1993

J. Clin. Invest.

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“…The results of these studies revealed, however, no sub stantial role of y-GT in total renal ammonia genesis under control and acidotic conditions [3,[23][24][25][26], which is in agreement with the rates of utilization of glutamine by y-GT, and is in good accord with our findings on LLC-PK, epithelia ( fig. 2.…”

Section: Discussionsupporting

confidence: 82%

“…This particular role of the hydrolytic activ ity of y-GT in the extracellular splitting of glu tamine and luminal ammoniagenesis, respec tively, has been studied recently in detail in vivo [23][24][25][26] and in vitro [34,35]. The results of these studies revealed, however, no sub stantial role of y-GT in total renal ammonia genesis under control and acidotic conditions [3,[23][24][25][26], which is in agreement with the rates of utilization of glutamine by y-GT, and is in good accord with our findings on LLC-PK, epithelia ( fig.…”

Section: Discussionmentioning

confidence: 99%

“…22], the y-glutamyl moiety of D-and L-glutamine is hydrolytically split, yielding D-or L-glutamate and ammonia [18, 21. 22], The role of extracellular (luminal] ammoniagene sis has been studied in detail in the lumen of rat proximal tubules [23][24][25][26], These studies, however, revealed no substantial role for lu minal y-GT activity in ammoniagenesis under control and acidotic conditions [23][24][25][26]. The present study, which was undertaken in an vit ro model utilizing LLC-PK] cultured epithe lia.…”

Section: Introductionmentioning

confidence: 99%

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Ammoniagenesis in Renal Cell Culture

Gstraunthaler¹,

Landauer²,

Pfaller³

1993

Kidney Blood Press Res

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In renal ammoniagenesis, two major pathways of glutamine metabolism have been described: (i) intracellular metabolism by phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase and (ii) extracellular metabolism by phosphate-independent glutaminase. The latter has been identified as the hydrolytic activity of the apically membrane-bound γ-glutamyl transpeptidase (γ-GT). The growth properties of cultured renal epithelia enable the study of in vitro extracellular metabolic properties occurring at the apical epithelial surface in the culture dish. Therefore, confluent epithelia of the LLC-PK₁ renal epithelial cell line were used to elucidate the role of extracellular (apical) hydrolysis of glutamine by γ-GT in LLC-PK₁ ammonia production. To distinguish between intra- and extracellular metabolism of glutamine, confluent LLC-PK₁ epithelia were incubated with either D-glutamine as substrate, which cannot be metabolized intracellularly by PDG, or with L-glutamine and hippurate to stimulate, and AT-125 (acivicin) to inhibit γ-GT activity, respectively. In addition, cellular uptake of the glutamate, extracellularly formed by γ-GT, was inhibited by D-aspartate. D-Glutamine (2 mM) did not increase ammonia formation above endogenous production levels, indicating the negligible role of extracellular hydrolysis of glutamine by γ-GT. After modulating γ-GT activity by hippurate or AT-125, almost identical ammonia production rates were found within the various experimental protocols, further confirming that extracellular metabolism of glutamine does not significantly contribute to LLC-PK₁ ammoniagenesis.

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“…42 Welbourne" investigated the enhanced renal ammoniagenesis in a study of chronic acidosis in rats. Increased urinary ammonia excretion was observed at elevated arterial ammonia levels.…”

Section: Lungmentioning

confidence: 99%

The Contribution of Various Organs to Ammonia Formation: A Review of Factors Determining the Arterial Ammonia Concentration

Huizenga

Gips²,

Tangerman

1996

Ann Clin Biochem

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Additional key phrases: hepatic encephalopathy; liver; metabolismThe arterial ammonia concentration-which is clinically regarded as the gold standard for blood ammonia determinations in hepatic encephalopathy (HE)-has narrow limits and a complex background. Several factors relating to single organs are of crucial importance, e.g. the ammonia concentration of the artery and the vein, the blood inflow and outflow, the weight of the organ and the enzymes which playa key role in the formation and metabolism of ammonia. In this review we attempt to provide a quantitative survey of the organs and mechanisms involved in maintaining ammonia uptake and release under normal physiological conditions with regard to liver failure and subsequently to other organs. METABOLISM OF AMMONIAAmmonia is derived mainly from deamination of the a-amino nitrogen of amino acids and is toxic to all animals, especiallyat elevated concentrations. Human tissue, therefore, initially detoxifies ammonia by converting it to glutamine for transport to the liver. Under normal conditions, deamination of glutamine and glutamate in the liver releases ammonia, which then is efficiently converted to the non-toxic nitrogen-rich compound urea, which is subsequently excreted into the urine. In liver failure, diminished urea synthetic capacity and portal-systemic shunting cause impairment of the physiological route of ammonia detoxification, leading to elevated arterial ammonia levels.'In mammals, ammonia is liberated by transamination followed by oxidative deamination Correspondence to: Mr J R Huizenga. of glutamate.P In this process alanine transaminase and glutamate transaminase catalyse the transfer of amino groups from most amino acids to form L-alanine from pyruvate or L-glutamate from a-ketoglutarate:Each transaminase is specific for one pair of substrates but not for the other pair. Since L-alanine is also a substrate for glutamate transaminase, all the amino nitrogen from amino acids that can undergo transamination can be concentrated in L-glutamate. In mammalian tissue L-glutamate is the only amino acid that undergoes oxidative deamination to ammonia. The reaction is catalysed by glutamate dehydrogenase and is reversible:The overall reaction of transamination followed by oxidative deamination is localized almost exclusively in the liver. Also in the liver, ammonia is fixated by carbon dioxide to form carbamoyl phosphate catalysed by carbamoyl phosphate synthetase:This is the first step in urea synthesis and takes place in liver mitochondria. The remaining main part of the urea cycle takes place in liver cytosol. The urea cycle will not be further discussed here. Ammonia generated by enteric bacteria is absorbed into the portal venous blood and transported to the liver, where it is converted into L-glutamate, L-glutamine and finally into urea. In addition to fixation of ammonia via the glutamate dehydrogenase reaction, formation of L-glutamine is catalysed by glutamine synthetase, 23

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Gamma glutamyltransferase contribution to renal ammoniagenesis in vivo

Cited by 22 publications

References 42 publications

Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

Ammoniagenesis in Renal Cell Culture

The Contribution of Various Organs to Ammonia Formation: A Review of Factors Determining the Arterial Ammonia Concentration

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