Dietary and Hormonal Regulation of Urea Cycle Enzymes in
Rat Liver

Christowitz, Denise; Mattheyse, F. J.; Balinsky, J.B.

doi:10.1159/000459160

Cited by 28 publications

(11 citation statements)

References 11 publications

(19 reference statements)

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“…Others confirmed these results in an unstated strain of rat [14] and in SpragueDawley rats [15]. We found that adrenalec tomy reduced all but argininosuccinate lyase in Wistar-Furth rats ingesting a 15 % casein diet.…”

Section: Discussionsupporting

confidence: 85%

Dexamethasone and Glucagon Cause Synergistic Increases of Urea Cycle Enzyme Activities in Livers of Normal But Not Adrenalectomized Rats

Snodgrass¹

1991

Enzyme

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Adrenalectomized and intact rats were given constant high-dose infusions of glucagon, 0.3 mg/kg per day for 7 days, with or without low-dose dexamethasone, 0.01 mg/kg daily, to test whether glucocorticoids potentiate glucagon induction of the 5 urea cycle enzymes as they do in cultured rat hepatocytes. Glucagon did not induce any of the urea cycle enzymes in adrenalectomized Sprague-Dawley rats and only induced argininosuccinate lyase (EC 4.3.2.1) in adrenalectomized inbred Wistar-Furth rats. Dexamethasone alone induced arginase in adrenalectomized and in intact Wistar-Furth rats and restored the other enzymes to normal levels in adrenalectomized rats. In intact Wistar-Furth rats, the combination of hormones gave synergistic increases of all 5 enzymes over the responses to each hormone alone, but in adrenalectomized rats the combination was only additive or less than additive compared with the sum of single hormone responses. The lack of synergism between the two hormones in adrenalectomized rats suggest that other factors play a role in glucagon induction of this cycle.

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Section: Discussionsupporting

confidence: 85%

Dexamethasone and Glucagon Cause Synergistic Increases of Urea Cycle Enzyme Activities in Livers of Normal But Not Adrenalectomized Rats

Snodgrass¹

1991

Enzyme

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“…In this report, we investigated the dynamics of various genes related to the greater urea cycle, an important biochemical pathway present in mammalian livers for nitrogen disposal. Many of these enzymes are known to be highly regulated by CS in the liver (Christowitz et al 1981; de Groot et al 1984; Gautier et al 1985). …”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Modeling of Acute and Chronic Effects of Methylprednisolone on Hepatic Urea Cycle Genes in Rats

Hazra¹,

DuBois

Almon

et al. 2008

Gene�Regul Syst Bio

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Corticosteroids (CS) regulate many enzymes at both mRNA and protein levels. This study used microarrays to broadly assess regulation of various genes related to the greater urea cycle and employs pharmacokinetic/pharmacodynamic (PK/PD) modeling to quantitatively analyze and compare the temporal profiles of these genes during acute and chronic exposure to methylprednisolone (MPL). One group of adrenalectomized male Wistar rats received an intravenous bolus dose (50 mg/kg) of MPL, whereas a second group received MPL by a subcutaneous infusion (Alzet osmotic pumps) at a rate of 0.3 mg/kg/hr for seven days. The rats were sacrificed at various time points over 72 hours (acute) or 168 hours (chronic) and livers were harvested. Total RNA was extracted and Affymetrix® gene chips (RG_U34A for acute and RAE 230A for chronic) were used to identify genes regulated by CS. Besides five primary urea cycle enzymes, many other genes related to the urea cycle showed substantial changes in mRNA expression. Some genes that were simply up- or down-regulated after acute MPL showed complex biphasic patterns upon chronic infusion indicating involvement of secondary regulation. For the simplest patterns, indirect response models were used to describe the nuclear steroid-bound receptor mediated increase or decrease in gene transcription (e.g. tyrosine aminotransferase, glucocorticoid receptor). For the biphasic profiles, involvement of a secondary biosignal was assumed (e.g. ornithine decarboxylase, CCAAT/enhancer binding protein) and more complex models were derived. Microarrays were used successfully to explore CS effects on various urea cycle enzyme genes. PD models presented in this report describe testable hypotheses regarding molecular mechanisms and quantitatively characterize the direct or indirect regulation of various genes by CS.

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“…Protein supplementation in rats is reported to increase ASS and ASL expression/activity in liver. However in the kidney, protein deficiency causes induction of these enzymes (11,56).…”

Section: Conversion Of L-citrulline To L-argininementioning

confidence: 99%

Therapeutic Use of Citrulline in Cardiovascular Disease

Romero

Platt

Caldwell

2006

Cardiovascular Drug Reviews

190

178

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L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide synthase (NOS) in the production of NO. Supplemental administration L-arginine has been shown to be effective in improving NO production and cardiovascular function in cardiovascular diseases associated with endothelial dysfunction, such as hypertension, heart failure, atherosclerosis, diabetic vascular disease and ischemia-reperfusion injury, but the beneficial actions do not endure with chronic therapy. Substantial intestinal and hepatic metabolism of L-arginine to ornithine and urea by arginase makes oral delivery very ineffective. Additionally, all of these disease states as well as supplemental L-arginine enhance arginase expression and activity, thus reducing the effectiveness of L-arginine therapy. In contrast, L-citrulline is not metabolized in the intestine or liver and does not induce tissue arginase, but rather inhibits its activity. L-citrulline entering the kidney, vascular endothelium and other tissues can be readily converted to L-arginine, thus raising plasma and tissue levels of L-arginine and enhancing NO production. Supplemental L-citrulline has promise as a therapeutic adjunct in disease states associated with L-arginine deficiencies.

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Dietary and Hormonal Regulation of Urea Cycle Enzymes in Rat Liver

Cited by 28 publications

References 11 publications

Dexamethasone and Glucagon Cause Synergistic Increases of Urea Cycle Enzyme Activities in Livers of Normal But Not Adrenalectomized Rats

Dexamethasone and Glucagon Cause Synergistic Increases of Urea Cycle Enzyme Activities in Livers of Normal But Not Adrenalectomized Rats

Pharmacodynamic Modeling of Acute and Chronic Effects of Methylprednisolone on Hepatic Urea Cycle Genes in Rats

Therapeutic Use of Citrulline in Cardiovascular Disease

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