Immunohistochemical localization of carbamoyl-phosphate synthetase (ammonia) in adult rat liver; evidence for a heterogeneous distribution.

Janzen, J. W. Gaasbeek; Lamers, Wouter H.; Moorman, Antoon F.M.; Graaf, A. De; Los, J. M.; Charles, R.

doi:10.1177/32.6.6373912

Cited by 124 publications

(76 citation statements)

References 5 publications

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“…(a) Prevention of circulatory changes by sodium nitroprusside abolished the nerve effects on the metabolism of the nitrogenous compounds but not on the exchange of glucose and lactate (Fig. 1). (b) Urea release is the result of a simple unidirectional pathway, which is predominantly located in the periportal area [28,29]. If a process is the result of a unidirectional pathway, an effect or the lack of an effect may be conclusively interpreted.…”

Section: Mode Of Nerve Actionmentioning

confidence: 99%

Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation

Balle

Jungermann

1986

European Journal of Biochemistry

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1. The nervous control of hepatic urea and glutamine release and of ammonia uptake was studied in the rat liver perfused in situ.2. Electrical stimulation of the nerve bundles around the hepatic artery and the portal vein resulted in a reduction of urea release, of glutamine output and of ammonia uptake. At the same time, as observed before Eur. J. Biochem. 123, 521 -5261, nerve stimulation led to a decrease of portal flow as well as to an increase of glucose release and a shift of lactate uptake to output.3. Noradrenaline infusion mimicked the nerve-dependent metabolic and hemodynamic changes in a first approximation only at the highly unphysiological concentration of 0.1 pM. It was without effect at 0.01 pM, which might be reached in the sinusoids as a result of overflow from the vasculature.4. In the presence of sodium nitroprusside nerve stimulation no longer reduced urea output, glutamine release and ammonia uptake or portal flow, yet it still increased glucose and lactate release.5. Phentolamine clearly reduced the alterations after nervous stimulation of urea output, ammonia uptake and portal flow, while propranolol was essentially not effective. The nerve-stimulation-dependent reduction of glutamine release was almost abolished in the presence of phentolamine and lowered to 50% by propranolol.6. Glucagon stimulated urea output but had no influence on glutamine release, ammonia uptake and portal flow. Nerve stimulation antagonized the glucagon-stimulated urea release.7. The present results suggest that in the perfused liver wsympathetic hepatic nerves regulate urea release, glutamine output and ammonia uptake predominantly by an indirect mechanism via hemodynamic alterations, but glucose release by a direct mechanism also in the absence of circulatory changes.The liver is innervated by sympathetic and parasympathetic nerves [l-31. It was shown previously that in the isolated perfused rat liver electrical stimulation of the nerve bundles around the hepatic artery and the portal vein resulted in an increase of glucose output, a switch from lactate uptake to output and a decrease of portal flow [4] combined with a change of the intrahepatic microcirculation [5, 61, a reduction of oxygen uptake [5,7] and an overflow of noradrenaline into the hepatic vein [8]. All nerve actions were predominantly aadrenergic. It was observed recently that hepatic nerve stimulation decreased ketogenesis [9]. Possible effects of nerve stimulation on hepatic 'nitrogen' metabolism have not been studied so far either in vivo or in the isolated perfused organ. Therefore it was the object of the present investigation to clarify whether the hepatic nerves can also regulate urea, glutamine and ammonia metabolism besides glucose and lactate exchange. A preliminary report on some of the findings has appeared previously [lo].

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Section: Mode Of Nerve Actionmentioning

confidence: 99%

Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation

Balle

Jungermann

1986

European Journal of Biochemistry

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“…2 The predominant expression of CPSase I and OTC within periportal hepatocytes effectively restricts the urea cycle to the liver. 3 In contrast, the three cytoplasmic enzymes of the urea cycle are expressed in many tissues. …”

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confidence: 99%

Mice deficient in the urea-cycle enzyme, carbamoyl phosphate synthetase i, die during the early neonatal period from hyperammonemia

et al. 1999

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The hepatic urea cycle detoxifies ammonia liberated by the degradation of amino acids, producing urea. 1 The cycle comprises two mitochondrial enzymes, carbamoyl phosphate synthetase (CPSase I) and ornithine transcarbamylase (OTC), and three cytoplasmic enzymes: argininosuccinic acid synthetase, argininosuccinate lyase, and arginase. 2 The predominant expression of CPSase I and OTC within periportal hepatocytes effectively restricts the urea cycle to the liver. 3 In contrast, the three cytoplasmic enzymes of the urea cycle are expressed in many tissues.

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“…Excess ammonia not used by urea synthesis is taken up with high affinity by a small perivenous hepatocyte population (so-called "perivenous scavenger cells") (1), which detoxifies ammonia by amidation of Glu (4). This reaction is catalyzed by Gln synthetase (GS), which is specifically expressed in this small population of hepatocytes surrounding the terminal hepatic venule but not in other hepatocytes (4)(5)(6). This high-affinity ammonia removal by perivenous hepatocytes thus prevents spillover of hepatic ammonia into the systemic circulation.…”

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Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

Qvartskhava

Lang

Görg

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Urea cycle defects and acute or chronic liver failure are linked to systemic hyperammonemia and often result in cerebral dysfunction and encephalopathy. Although an important role of the liver in ammonia metabolism is widely accepted, the role of ammonia metabolizing pathways in the liver for maintenance of whole-body ammonia homeostasis in vivo remains ill-defined. Here, we show by generation of liver-specific Gln synthetase (GS)-deficient mice that GS in the liver is critically involved in systemic ammonia homeostasis in vivo. Hepatic deletion of GS triggered systemic hyperammonemia, which was associated with cerebral oxidative stress as indicated by increased levels of oxidized RNA and enhanced protein Tyr nitration. Liver-specific GS-deficient mice showed increased locomotion, impaired fear memory, and a slightly reduced life span. In conclusion, the present observations highlight the importance of hepatic GS for maintenance of ammonia homeostasis and establish the liver-specific GS KO mouse as a model with which to study effects of chronic hyperammonemia.hepatic encephalopathy | metabolic zonation | oxidative stress | RNA oxidation | glutamine

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Immunohistochemical localization of carbamoyl-phosphate synthetase (ammonia) in adult rat liver; evidence for a heterogeneous distribution.

Cited by 124 publications

References 5 publications

Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation

Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation

Mice deficient in the urea-cycle enzyme, carbamoyl phosphate synthetase i, die during the early neonatal period from hyperammonemia

Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

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