Ammonia Production Restoration Kit
Ammonia Production Restoration Kit
This is an important measure and indication of how healthy your liver is, as higher levels of ammonia in your blood indicates your liver is not working properly. In some cases it can lead to a disease known as Hepatic Encephalopathy, which directly impacts the brains with the plethoric amounts of ammonia in your blood.
Ammonia is a byproduct your body creates as it processes protein, so it is important to deal with it should your results be average or poor.
Maintaining acid-base homeostasis is critical for normal health. Acid-base disorders lead to such clinical problems as:
In neonates and children
Nausea and Vomiting
Increased Susceptibility To Cardiac Arrhythmias
Decreased Cardiovascular Catecholamine Sensitivity
Bone Disorders Including Osteoporosis and Osteomalacia
Skeletal Muscle Atrophy
Paresthesia & Coma
Important correlations between abnormal acid-base homeostasis and mortality, with both an elevated and a lowered serum bicarbonate predicting increased mortality in patients both with and without chronic kidney disease (CKD) have been suggested.
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Metabolism of the normal amino-acid content of the typical Western diet results in signiﬁcant rates of endogenous acid production, averaging 0.8-1.0mmol•kg-1•day- 1. This continuous acid load is buffered rapidly by intracellular and extracellular buffers, of which the CO 2 -HCO 3 - buffer system is the most relevant. Protons (H + ) are buffered by bicarbonate (HCO 3 - ), forming carbonic acid (H 2 CO 3 ), which then rapidly dissociates to CO 2 and water. CO 2 is eliminated through normal respiration. While highly effective at buffering endogenous acid production, equimolar bicarbonate is used in the process, thereby depleting total body bicarbonate levels. A critical function of the kidneys is to generate “new” bicarbonate to replenish that bicarbonate utilized for buffering acid loads. The kidneys have two major functions in acid-base homeostasis: 1) reabsorbing ﬁltered bicarbonate and 2) generating new bicarbonate. Renal new bicarbonate generation involves both ammonia metabolism and titratable acid excretion. Under basal conditions, ammonia metabolism, which includes net ammoniagenesis and renal epithelial cell ammonia transport leading to urinary ammonia excretion, is the greater component of new bicarbonate generation
Ammonia is produced in the kidney and then is selectively transported either into the urine or the renal vein. The proportion of ammonia that the kidney produces that is excreted in the urine varies dramatically in response to physiological stimuli, and only urinary ammonia excretion contributes to acid-base homeostasis.
Ammonia production pathway
Ammonia metabolism involves integrated function of multiple portions of the kidney. Ammonia is produced by almost all renal epithelial cells, but the proximal tubule is the primary site for physiologically relevant ammoniagenesis. Studies examining dissected renal segments, show that all have the capability to synthesize ammonia using glutamine as their primary metabolic substrate. Metabolism of each glutamine molecule leads to generation of 2 NH 4 + and 2 HCO 3 − ions when glutamine is metabolized through phosphate-dependent glutaminase (PDG), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase (PEPCK) during metabolic acidosis and hypokalemia.
1. Predominant pathway involves the enzyme PDG. PDG is present inside mitochondria and metabolizes glutamine to glutamate, producing NH 4 + . Glutamate then undergoes further metabolism through multiple pathways. 1.1. The major pathway involves GDH, resulting in production of α- ketoglutarate (α-KG) and NH 4 + . GDH-mediated metabolism of glutamate to form α-KG is the quantitatively predominant mechanism, and is regulated in parallel with changes in total renal ammoniagenesis.
1.2. Transamination of glutamate via glutamicoxaloacetic transaminase (GOT) does not release NH 4 + , but the aspartate produced can be metabolized through the purine nucleotide cycle (PNC), forming fumarate and releasing NH 4 + . The PNC pathway mediates only a minor role in overall ammoniagenesis.
1.3. Glutamate can also be metabolized through glutamate decarboxylase to form γ-aminobutyric acid (GABA), and this may account for as much as 25% of glutamate oxidation in the renal cortex, but this pathway does not alter net ammoniagenesis since GABA metabolism to succinate semialdehyde via the enzyme γ-aminobutyrate transaminase results in regeneration of glutamate.
1.4. Glutamate can also be converted back to glutamine via the enzyme glutamine synthetase. Because this reaction utilizes NH 4 + as a cosubstrate, it results in decreased net NH 4 + formation.
2. Glutamine can also be metabolized by γ-glutamyl transpeptidase (γ-GT), also known as phosphate-independent glutaminase, although this is unlikely to be a major mechanism of renal ammoniagenesis. The glutamate resulting from γ- GT-dependent glutamine metabolism is then transported into the cell, where it can undergo further metabolism through GDH, resulting in further NH 4 + production.
3. Another pathway involves sequential metabolism through glutamine ketoacid aminotransferase and ω-amidase, forming α-KG and releasing NH 4 + . Quantitative assessments suggest this pathway does not contribute substantially to net ammoniagenesis. Ammonia from the gut microbiota Certain common intestinal bacteria (Escherichia coli and Lactobacillus plantarum) primarily reduce nitrite to ammonia rather than to NO. In healthy subjects, under ordinary physiological conditions, the bulk of ammonia generated in the lower GI tract is then excreted in the body fluids and metabolized by the liver hepatocytes where ammonia and carbon dioxide are enzymatically converted to carbamoyl phosphate, which enters the series of reactions called the “Urea Cycle” leading to urea formation and its elimination by the kidney. When ammonia production is excessive, portal blood-carrying ammonia can bypass the liver leading to hyperammonemia:
- Ammonia in the blood freely permeates through the blood-brain barrier and high levels (>100 μM) have toxic effects on the central nervous system leading to encephalopathy and eventually coma.
- Patients with liver cirrhosis very frequently develop hepatic encephalopathy (HE).
- In the absence of liver failure, hyperammonemic coma has been attributed to sepsis by urease capable microorganisms such as Klebsiella pneumonia. Therapeutics for Hepatic Encephalopathy (HE)
Classic therapeutic approaches for HE:
- Reduction of systemic ammonia levels via antibiotic treatment (to kill intestinal ammonia producing bacteria)
- Administration of non-absorbable sugars, such as lactulose and lactitol
- Lactulose (β-galactosido-frutose) – For HE treatment, a relatively large oral dosage three or four times a day with episodic diarrhea and constant flatulence almost a certain side effect is necessary. People who take lactulose at this dosage generally end up wearing an adult diaper and plastic pants for any activities away from home or at night (with a chux pad for the bed) because the diarrhea can occur swiftly and without much warning.
- Lactitol (β-galactosido-sorbital) – Less side effects, due to a more predictable cathartic effect.
In the large intestine lactulose is broken down by the action of colonic bacteria primarily to lactic acid, and also to small amounts of formic and acetic acids. This acidification favors the formation of the non-absorbable ammonium ion from ammonia and reduces its concentration in plasma. Increased acidification of the colonic content due to the presence of lactulose favors the microbiota conversion of nitrite to NO instead of ammonia by the known acid-dependent mechanism.