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Related Concept Videos

Inorganic Nitrogen Assimilation01:22

Inorganic Nitrogen Assimilation

Nitrogen is an essential element in biological systems, forming a crucial component of proteins, nucleic acids, and other cellular constituents. Many bacteria and archaea acquire nitrogen in the form of nitrate (NO₃⁻) or ammonia (NH₃), which are then assimilated into biomolecules through specific enzymatic pathways.Assimilatory Nitrate ReductionWhen nitrate enters the cell, it undergoes a two-step reduction process known as assimilatory nitrate reduction. Initially, the enzyme nitrate reductase...
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The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
Amino Acid Catabolism01:18

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Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
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Overview of Nitrogen Metabolism

Nitrogen is a very important element for life because it is a major constituent of proteins and nucleic acids. It is a macronutrient, and in nature, it is recycled from organic compounds and stored in the form of  ammonia, ammonium ions, nitrate, nitrite, or  nitrogen gas by many metabolic processes. Many of these metabolic processes are carried out only by prokaryotes.
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Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which provide...
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Hepatic Glucose Production, Ureagenesis, and Lipolysis Quantified using the Perfused Mouse Liver Model
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Gut ammonia production and its modulation.

Manuel Romero-Gómez1, María Jover, J Jorge Galán

  • 1Unit for the Clinical Management of Digestive Diseases & ciberehd, Hospital Universitario de Valme, Universidad de Sevilla, 41014 Sevilla, Spain. mromerog@supercable.es

Metabolic Brain Disease
|December 11, 2008
PubMed
Summary

Systemic hyperammonemia in cirrhosis is linked to hepatic encephalopathy. New research suggests the small intestine, not just gut bacteria, is a key ammonia source, potentially via glutaminase activity, influencing disease severity.

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Area of Science:

  • Hepatology
  • Gastroenterology
  • Neuroscience

Background:

  • Systemic hyperammonemia is central to cirrhosis and hepatic encephalopathy pathogenesis.
  • Existing treatments often target gut bacteria, but the precise ammonia source remains debated.
  • The correlation between ammonia levels and neurological impairment requires further clarification.

Purpose of the Study:

  • To investigate the source of ammonia production in systemic hyperammonemia in cirrhosis.
  • To explore the role of the small intestine and glutaminase activity in ammonia generation.
  • To examine potential genetic modulators of ammonia production and hepatic encephalopathy risk.

Main Methods:

  • Analysis of ammonia levels in germ-free and conventional rats post-porto-caval shunting.
  • Measurement of hyperammonemia in portal drained viscera of cirrhotic patients.
  • Assessment of ammonia increase after oral glutamine challenge.
  • Investigation of glutaminase gene alterations, including the TACC haplotype.

Main Results:

  • Hyperammonemia levels were similar in germ-free and non-germ-free rats, suggesting non-bacterial sources.
  • Cirrhotic patients showed peak hyperammonemia in portal drained viscera, primarily from glutamine deamination.
  • Rapid ammonia increase post-glutamine challenge supports small intestine origin.
  • Increased intestinal glutaminase activity appears responsible for systemic hyperammonemia.

Conclusions:

  • The small intestine, through glutaminase-mediated deamidation of glutamine, is a significant source of systemic hyperammonemia in cirrhosis.
  • This challenges the traditional focus solely on colonic bacteria.
  • Genetic factors like the TACC haplotype in the glutaminase gene may influence ammonia production and hepatic encephalopathy risk.