154 THE CONTRIBUTIONS OF DE NOVO ARGININE GENERATION AND ARGINASE ACTIVITY TO WHOLE BODY ARGININE METABOLISM IN ACUTE LIVER FAILURE

In acute liver failure (ALF), the hyperdynamic circulation is believed to be the result of overproduction of nitric oxide (NO) in the splanchnic circulation. However, it has been suggested that arginine concentrations (the substrate for NO) are believed to be decreased, limiting substrate availability for NO production. To characterize the metabolic fate of arginine in early-phase ALF, we systematically assessed its interorgan transport and metabolism and measured the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in a porcine model of ALF. Female adult pigs (23–30 kg) were randomized to sham ( N = 8) or hepatic devascularization ALF ( N = 8) procedure for 6 h. We measured plasma arginine, citrulline, ornithine levels; arginase activity, NO, and ADMA. Whole body metabolic rates and interorgan flux measurements were calculated using stable isotope-labeled amino acids. Plasma arginine decreased >85% of the basal level at t = 6 h ( P < 0.001), whereas citrulline and ornithine progressively increased in ALF ( P < 0.001 and P < 0.001, vs. sham respectively). No difference was found between the groups in the whole body rate of appearance of arginine or NO. However, ALF showed a significant increase in de novo arginine synthesis ( P < 0.05). Interorgan data showed citrulline net intestinal production and renal consumption that was related to net renal production of arginine and ornithine. Both plasma arginase activity and plasma ADMA levels significantly increased in ALF ( P < 0.001). In this model of early-phase ALF, arginine deficiency or higher ADMA levels do not limit whole body NO production. Arginine deficiency is caused by arginase-related arginine clearance in which arginine production is stimulated de novo.

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De Novo Mutations in POLG Presenting with Acute Liver Failure or Encephalopathy

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0b013e31817d9cad ◽

2009 ◽

Vol 49 (1) ◽

pp. 126-129 ◽

Cited By ~ 11

Author(s):

Richard E Lutz ◽

David Dimmock ◽

Eric S Schmitt ◽

Qing Zhang ◽

Lin-Ya Tang ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

De Novo ◽

De Novo Mutations

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Crossroad of infection and autoimmunity in acute liver failure: a case report

Egyptian Liver Journal ◽

10.1186/s43066-021-00083-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Akash Roy ◽

Sunil Taneja ◽

Arka De ◽

Ashim Das ◽

Ajay K. Duseja ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Autoimmune Hepatitis ◽

De Novo ◽

Dramatic Improvement ◽

Case Presentation ◽

Wide Range ◽

Syndromic Diagnosis ◽

Initial Improvement ◽

Tropical Infections

Abstract Background Acute liver failure (ALF) is a syndromic diagnosis, consisting of jaundice, coagulopathy, and any degree of encephalopathy in a patient without pre-existing liver disease within 26 weeks of the onset of symptoms. Autoimmune hepatitis has a wide range of presentations and can rarely present as ALF, which frequently tends to be autoantibody negative. Tropical infections like dengue, malaria, and leptospirosis, which present as mimickers of ALF, always remain a differential diagnosis of ALF and mandate an etiology specific management. In rare cases, such infections themselves act as a trigger for autoimmunity. We report a case of diagnostic crossroads of infection and autoimmunity, presenting as acute liver failure and describe the challenges in management. Case presentation A 25-year-old female presented with a syndromic diagnosis of acute liver failure with possibility of tropical illness-related ALF mimic on account of positive Leptospira serology. After initial improvement, there was a rebound worsening of liver functions which prompted a liver biopsy. Biopsy narrowed the differential to Leptospira-associated hepatitis and severe auto-immune hepatitis. Trial of low dose steroid was given which led to dramatic improvement. Conclusion Tropical infections can present as ALF mimics and can themselves act as triggers for autoimmunity. Distinguishing such cases from de-novo acute severe autoimmune hepatitis is difficult and requires therapeutic brinksmanship. An early trial of steroid is mandated but comes with its own challenges.

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Arginase II Plays a Central Role in the Sexual Dimorphism of Arginine Metabolism in C57BL/6 Mice

Journal of Nutrition ◽

10.1093/jn/nxaa318 ◽

2020 ◽

Vol 150 (12) ◽

pp. 3133-3140

Author(s):

Mahmoud A Mohammad ◽

Inka C Didelija ◽

Juan C Marini

Keyword(s):

Sexual Dimorphism ◽

Plasma Concentration ◽

Arginase Activity ◽

Whole Body ◽

Synthesis Rate ◽

Male Mice ◽

Arginine Metabolism ◽

Female Mice ◽

Arginase Ii ◽

Endogenous Synthesis

ABSTRACT Background Sex differences in plasma concentration of arginine and arginase activity of different tissues have been reported in mice. In addition, male but not female C57BL/6 mice have a dietary arginine requirement for growth. Objective The goal of this research was to test the hypothesis that arginase II is a key factor in the sexual dimorphism of arginine metabolism. Methods Young adult male and female wild type (WT), and heterozygous and arginase II knockout mice on a C57BL/6 background mice were infused with labeled citrulline, arginine, ornithine, phenylalanine, and tyrosine to determine the rates of appearance and interconversion of these amino acids. Tissue arginase activity was measured in the liver, heart, jejunum, kidney, pancreas, and spleen with an arginine radioisotope. The effect of genotype, sex, and their interaction was tested. Results Female mice produced ∼36% more citrulline than their male littermates, which translated into a greater arginine endogenous synthesis, flux, and plasma concentration (42, 6, and 27%, respectively; P < 0.001). Female mice also had a greater phenylalanine flux (10%) indicating a greater rate of whole protein breakdown; however, they had a lower protein synthesis rate than males (18%; P < 0.001). The ablation of arginase II reduced the production of citrulline and the de novo synthesis of arginine in females and increased the rate of appearance of arginine and plasma arginine concentration in male mice (16 and 22%, respectively; P < 0.001). No effect of arginase II deletion, however, was observed for whole-body protein kinetics. Arginase II activity was present in the pancreas, kidney, jejunum, and spleen; WT females had a ∼2-fold greater renal arginase activity than their WT counterparts. Conclusions A clear sexual dimorphism exists in the endogenous synthesis of arginine and its disposal. Female mice have a greater arginine availability than their male littermates. The ablation of arginase II increases arginine availability in male mice.

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