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Abstract: As glutamate and ammonia play a pivotal role in nitrogen homeostasis, their production is mediated by various enzymes that are widespread in living organisms. Here, we report on an effective electrophoretic method to monitor these enzymes. The in gel activity visualization is based on the interaction of the products, glutamate and ammonia, with glutamate dehydrogenase (GDH, EC: 1.4.1.2) in the presence of either phenazine methosulfate (PMS) or 2,6-dichloroindophenol (DCIP) and iodonitrotetrazolium (INT). The intensity of the activity bands was dependent on the amount of proteins loaded, the incubation time and the concentration of the respective substrates. The following enzymes were readily identified: glutaminase (EC: 3.5.1.2), alanine transaminase (EC: 2.6.1.2), aspartate transaminase (EC: 2.6.1.1), glycine transaminase (EC: 2.6.1.4), ornithine oxoacid aminotransferase (EC: 2.6.1.13), and carbamoyl phosphate synthase I (EC: 6.3.4.16). The specificity of the activity band was confirmed by high pressure liquid chromatography (HPLC) following incubation of the excised band with the corresponding substrates. These bands are amenable to further molecular characterization by a variety of analytical methods. This electrophoretic technology provides a powerful tool to screen these enzymes that contribute to nitrogen homeostasis in Pseudomonas fluorescens and possibly in other microbial systems. [Copyright &y& Elsevier]

Hyperammonemia leads to neurotoxic levels of brain ammonia and is a major factor involved in the pathogenesis of hepatic encephalopathy (HE). Ammonia-lowering treatments primarily involve two strategies: inhibiting ammonia production and/or increasing ammonia removal. Targeting the gut has been the primary focus for many years, with the goal of inhibiting the generation of ammonia. However, in the context of liver failure, extrahepatic organs containing ammonia metabolic pathways have become new potential ammonia-lowering targets. Skeletal muscle has the capacity to remove ammonia by producing glutamine through the enzyme glutamine synthetase (amidation of glutamate) and, given its large mass, has the potential to be an important ammonia-removing organ. On the other hand, glutamine can be deaminated to glutamate by phosphate-activated glutaminase, thus releasing ammonia (ammonia rebound). Therefore, new treatment strategies are being focused on stimulating the removal of both ammonia and glutamine. [ABSTRACT FROM AUTHOR]

Valproate overdose, extensively described in adults and older children, has been reported in only 1 newborn: a 26-day-old female who developed a severe cerebral edema leading to a fatal outcome. Therefore, the consequences of valproate overdose are largely unknown in the neonatal period. Here, we present the clinical evolution of a 6-day-old newborn who developed hyperammonemic encephalopathy after the accidental administration of 310 mg/kg of oral valproate in a single dose. Despite the very high valproate and blood ammonia levels, he did not develop life-threatening complications and he completely recovered without sequels. His brain magnetic resonance imaging showed symmetric focal T1 prolonged signals in both globi pallidi that completely resolved over time, a neuroimaging pattern that was not previously described in valproate overdose. Our case report suggests that valproate overdose in newborns can be completely reversible even when the valproate and ammonium blood levels are very high. [ABSTRACT FROM AUTHOR]

Viable ova of Ascaris lumbricoides, an indicator organism for pathogens, are frequently found in feces-derived compost produced from ecological toilets, demonstrating that threshold levels of time, temperature, pH, and moisture content for pathogen inactivation are not routinely met. Previous studies have determined that NH3 has ovicidal properties for pathogens, including Ascaris ova. This research attempted to achieve Ascaris inactivation via NH3 under environmental conditions commonly found in ecological toilets and using materials universally available in an ecological sanitation setting, including compost (feces and sawdust), urine, and ash. Compost mixed with stored urine and ash produced the most rapid inactivation, with significant inactivation observed after 2 weeks and with a time to 99% ovum inactivation (T99) of 8 weeks. Compost mixed with fresh urine and ash achieved a T99 of 15 weeks, after a 4-week lag phase. Both matrices had relatively high total-ammonia concentrations and pH values of >9.24 (pKa of ammonia). In compost mixed with ash only, and in compost mixed with fresh urine only, inactivation was observed after an 11-week lag phase. These matrices contained NH3 concentrations of 164 to 173 and 102 to 277 mg/liter, respectively, when inactivation occurred, which was below the previously hypothesized threshold for inactivation (280 mg/liter), suggesting that a lower threshold NH3 concentration may be possible with a longer contact time. Other significant results include the hydrolysis of urea to ammonia between pH values of 10.4 and 11.6, above the literature threshold pH of 10. [ABSTRACT FROM AUTHOR]

Abstract: Under cold acclimated conditions, goldfish (Carassius auratus) express an interlamellar cell mass (ILCM) which limits diffusive ion loss but may also impede branchial ammonia excretion (J amm). In the present study, goldfish were subjected to a 2-week 5 or 25°C acclimation in order to modulate the degree of ILCM gill coverage and determine potential effects on J amm. 25°C-fish displayed gill coverage which was significantly lower than the 5°C-fish, though the ILCM was not completely absent in these fish. 5°C-fish demonstrated J amm values approximately 60% lower than those of 25°C-fish. The magnitude of anterior (branchial) J amm strongly correlated with gill coverage (r 2 =0.83), suggesting that the ILCM may impede branchial J amm. Divided chamber experiments demonstrated that relative to the 25°C-fish, 5°C-fish relied more upon posterior routes of excretion. In response to high external ammonia (HEA; 1.5mM NH4HCO3) exposures, 25°C-fish displayed ammonia uptake while 5°C-fish maintained excretion against HEA, suggesting that the ILCM may act as a barrier preventing ammonia uptake. In summary, the ILCM appears to impede branchial J amm, such that 5°C-rely more on extra-branchial routes of excretion. We hypothesize that gill remodeling in these fish may be intimately tied to physiological adjustments on the whole-body scale. [Copyright &y& Elsevier]

Background The diffusion of high-performance analytical technology has opened prospects for breath diagnosis as a non-invasive diagnostic tool. In this study, ion mobility spectrometry (IMS) and cavity ring-down spectroscopy (CRDS) techniques were used to analyse ammonia gas (NH3) in real-time in breath from patients undergoing haemodialysis (HD) treatment and any correlation with blood urea nitrogen (BUN) levels and Kt/V were investigated. Methods We studied 20 patients on intermittent HD treatment. The first breath samples were taken before the start of dialysis and further breath samples were taken every hour during the treatment and after the end of the session. An evaluation was also made of 20 healthy volunteers, acting as controls [healthy subjects (HS)]. Results Breath ammonia concentrations were higher in CRDS-HD (914.5 ± 301.4 versus 280 ± 120 parts per billion (p.p.b.), P < 0.0001) and IMS-HD patients (964.4 ± 402.4 versus 280 ± 120 p.p.b., P < 0.0001) than in HS. We assessed real-time variations in the levels of NH3 and showed a continuous decrease in the levels of NH3. Expired NH3 correlated directly with BUN levels, both in the IMS-HD (P = 0.002; r = 0.84; P = 0.009; r = 0.76) and in the CRDS-HD group (P = 0.005; r = 0.80; P = 0.008; r = 0.77), respectively, both before and at the end of dialysis. A direct correlation with Kt/V was found in both groups studied (IMS-HD: P = 0.003; r = 0.82; CRDS-HD: P = 0.006; r = 0.79). Conclusions Breath monitoring of NH3 with IMS and CRDS techniques could be useful to assess the real-time clinical status of patients during HD. By using pre-dialysis ammonia values, an approximate calculation of the Kt/Vurea ratio can be established. [ABSTRACT FROM PUBLISHER]

Ammonia is produced continuously in the body. It crosses the blood-brain barrier readily and at increased concentration it is toxic to the brain. A highly integrated system protects against this: ammonia produced during metabolism is detoxified temporarily by incorporation into the non-toxic amino acid glutamine. This is transported safely in the circulation to the small intestine, where ammonia is released, carried directly to the liver in the portal blood, converted to non-toxic urea and finally excreted in urine. As a result, plasma concentrations of ammonia in the systemic circulation are normally very low (<40 μmol/L). Hyperammonaemia develops if the urea cycle cannot control the ammonia load. This occurs when the load is excessive, portal blood from the intestines bypasses the liver and/or the urea cycle functions poorly. By far, the commonest cause is liver damage. This review focuses on other causes in adults. Because they are much less common, the diagnosis may be missed or delayed, with disastrous consequences. There is effective treatment for most of them, but it must be instituted promptly to avoid fatality or long-term neurological damage. Of particular concern are unsuspected inherited defects of the urea cycle and fatty acid oxidation presenting with catastrophic illness in previously normal individuals. Early identification of the problem is the challenge. [ABSTRACT FROM AUTHOR]

In order to evaluate the effect of different inclusion levels of mulberry (M. alba Linn.) cv. Cubana on the fermentation and reduction of the rumen methanogenesis in river buffaloes (Bubalus bubalis), an in vitro fermentation was performed and five levels of inclusion of M. alba L. cv. Cubana (0, 15, 20, 25 y 30 %) were assessed in a diet based on star grass (Cynodon nlemfuensis). The volume of gas and methane accumulated was determined at 4, 8, 12, and 24 h of fermentation, as well as the concentration of total and individual short chain fatty acids (SCFA), the ammonia (NH3), and the pH at 0, 4, 8, 12, and 24 h of incubation. The inclusion of M. alba L. cv. Cubana increased the production of gas accumulated at 24 h of fermentation, compared with the treatment containing only star grass. The different mulberry inclusion levels reduced the methane production in the rumen, compared with the control. The 30 % was the level that reduced it the most. The concentration of total and individual SCFA was not affected, nor that of NH3. It was concluded that the inclusion levels of 15, 20, 25, and 30 % of M. alba L. cv. Cubana did not affect the end products of the fermentation and reduced the in vitro rumen methane production. The 30 % was the level that reduced the most the rumen methanogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Osmoregulation is an essential physiological process for the majority of aquatic crustaceans since it enables them to cope with the changes/discrepancies between the ion concentrations within their bodies and the aquatic environments they inhabit. With the exception of strict osmoconformers, crustaceans living in all aquatic environments continually regulate their hemolymph osmolytes and ultimately, the strategy and strength of this process dictate the diversity of habitats a crustacean can successfully occupy. While the degree of the osmoregulatory response is largely salinity dependent, the actual strength is highly species-specific. This has obvious and significant implications to the crustacean aquaculture industry, a multi-billion dollar industry that is continuously growing worldwide. Unfortunately, to date, a comprehensive review discussing the implications of this crucial process in crustaceans from an aquaculture perspective is lacking. Since crustacean aquaculture is almost exclusively based on large decapods, which also forms the main body of literature, they will therefore be the main focus of review. With basic background information on the regulatory mechanisms briefly described as a foundation for necessary knowledge, the implications of increased osmoregulatory demands to crustacean aquaculture is discussed extensively based on recent literature and research conducted in our laboratory. This includes the various factors that may influence osmoregulatory abilities, the causes leading to reduced productivity at sub-optimal salinities, potential methods that may broaden tolerable salinity ranges and how osmoregulation may interact with another important physiological process, i.e. ammonia excretion, which is crucial for cultured crustaceans. At the end of the review, future research directions are suggested to advance our understanding regarding this complex process that could substantially affect crustacean aquaculture productivity. [Copyright &y& Elsevier]

Cirrhotic patients exhibit disturbed melatonin homeostasis, which may lead to sleep disturbances, but an influence on tHE3 HE3patic encephalopathy has not been elucidated. Aim. In tHE3 present study, tHE3 association ofmelatonin levels in serumand ascitic fluid and ammonia concentration related to tHE3 intensity of HE3patic encephalopathy (HE3) was investigated.Material andMethods. THE3 study included 90 alcoholic patients with HE3patic encephalopathy and 30 HE3althy volunteers (C). Patients were divided in three groups according to 0-4 West-Haven Score: HE31 (n = 28), HE32 (n = 30), and HE33 (n = 32). Melatonin was measured by radioimmune assay. Results. In fasting patients with HE3patic encephalopathy we noted higHE3r melatonin serum levels [pg/mL] than in HE3althy subjects groups: C-11.3±3.9, HE31 - 34.3±12.2 (P < 0.01), HE32-54.8±23.9, and HE33-119.8±96.4 (P < 0.001). No correlation between melatonin and ammonia levels was found.Melatonin was detected in ascetic fluid in 24 patients of group HE32 and 27 patients of group HE32 of HE3patic encephalopathy. Conclusions. Our results suggest that high blood levels of melatonin in cirrhotic liver patients may account for some of tHE3 clinical manifestations of HE3patic encephalopathy, for example, daytime sleepiness, fatigue. [ABSTRACT FROM AUTHOR]

Glutamate dehydrogenase (GDH) catalyzes the reversible inter-conversion of glutamate to α-ketoglutarate and ammonia. High levels of GDH activity is found in mammalian liver, kidney, brain, and pancreas. In the liver, GDH reaction appears to be close-to-equilibrium, providing the appropriate ratio of ammonia and amino acids for urea synthesis in periportal hepatocytes. In addition, GDH produces glutamate for glutamine synthesis in a small rim of pericentral hepatocytes. Hence, hepatic GDH can be either a source for ammonia or an ammonia scavenger. In the kidney, GDH function produces ammonia from glutamate to control acidosis. In the human, the presence of two differentially regulated isoforms (hGDH1 and hGDH2) suggests a complex role for GDH in ammonia homeostasis. Whereas hGDH1 is sensitive to GTP inhibition, hGDH2 has dissociated its function from GTP control. Furthermore, hGDH2 shows a lower optimal pH than hGDH1. The hGDH2 enzyme is selectively expressed in human astrocytes and Sertoli cells, probably facilitating metabolic recycling processes essential for their supportive role. Here, we report that hGDH2 is also expressed in the epithelial cells lining the convoluted tubules of the renal cortex. As hGDH2 functions more efficiently under acidotic conditions without the operation of the GTP energy switch, its presence in the kidney may increase the efficacy of the organ to maintain acid base equilibrium. [ABSTRACT FROM AUTHOR]

The living environment distress is connected currently not only with industrial production but also agriculture is biggest producer of toxic gas - ammonia (NH3) .Emissions of that gas originate mainly in the farm animals breeding and generate within storage and handling with farmyard manure, slurry, poultry excrements and litter. Agriculture influences considerably landscape has impact on basic effect on soil, water and air. In assessing experiment the preparation Biopolym FZT rumen metabolism and N-balance was found positive effects in terms of increased ammonia nitrogen, the number of ciliates and the reduction of N-compounds in feces. Confirmed the impact on the ammonia content in well-ventilated dairy stable. The economic evaluation depends on the exercise price of milk. In the experiments continued. [ABSTRACT FROM AUTHOR]

The aim of the study was to quantify the ammonia concentrations from the air of dairy cattle tie-stall barns and to compare it with threshold limits recommended in our country and in other countries. The significance of interactions between ammonia concentration and air temperature, relative humidity and air flow velocity was also determined. Two measurements were done in each barn, in the morning and in the evening of the same day. The Mann-Whitney U test indicated significant differences between the two measurements only for the ammonia concentrations in the air (p=0.003). In 20% of the investigated cattle barns the ammonia concentration was bellow 10 ppm, in 20% of these it varied from 11 and 26 ppm while in 60% of these, it exceeded 26 ppm. There was a significantly positive correlation between relative humidity and ammonia concentration in all barns, both for the morning (r=0.57, p=0.008) and for the evening (r=0.64, p=0.002) measurements. Assuming an ammonia threshold limit of 26 ppm, 60% of the dairy cattle barns in this study exceeded this recommended limit, indicating a need for improved housing conditions in the future. [ABSTRACT FROM AUTHOR]

The effects of different levels of energy and protein rations on rumen fluid, pH, ammonia, urea levels, kinds and numbers of species of protozoa in sheep are examined in the present experiment. Six male, Merino sheep were utilized in a 6 X 6 Latin square design. The rations were prepared as standard protein and standard energy level /(S-Group 1); low energy (LE-Group 2); low protein (LP-Group 3); high protein (HP-Group 4); high energy (HE-Group 5) and 10 g/day bicarbonate added to the high energy (HE+HCO3-Group 6). The experimental period extended to 10 days feeding period for each ration. Rumen fluid samples were taken from animals 0 hours before feeding as well as in the 2nd and the 4th hours after feeding during the last two days of feeding period. The end of the experiment time and feed factor showed statistically significant differences in pH values (P<0.05). The lowest pH level was observed in sheep fed ration HE+HCO3 before feeding time and pH levels were not statistically significant in the 2nd and 4th hours after feeding. It was found that the ammonia level in animals fed HP ration was the lowest (P<0.05) before feeding. Differences among time factors were found to be statistically significant (P<0.05) before feeding and 4th hours after feeding. Among the protozoa species Ento- dinium minimum was the most common species. Differences among feed factors for Entodinium caudatum level are found to be statistically significant (P<0.05). [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a complication of cirrhosis, the severity of which can range from subtle, neurocognitive dysfunction (minimal HE) to more apparent and severe cognitive and motor manifestations with increasing grades of the condition (overt HE). Current treatment options are targeted at reducing the levels of ammonia and other gut-derived toxins, the purported culprits behind the pathogenesis of HE. One of these therapeutic options, the nonsystemic antibiotic rifaximin, is efficacious for the treatment of minimal and overt HE. However, HE may be a cyclic condition in which patients with overt HE enter remission following treatment and then relapse. Thus, safe, effective and well-tolerated treatments are needed to maintain HE remission. Rifaximin maintained HE remission more effectively than placebo in a large, randomized controlled trial. Rifaximin is safe and well-tolerated for the treatment of minimal and overt HE and for the maintenance of HE remission. [ABSTRACT FROM AUTHOR]

Background: Female carriers of ornithine transcarbamylase deficiency (OTCD) have nearly normal rates of total urea synthesis, but they derive less urea from systemic glutamine amide nitrogen than do healthy persons. Objective: The objective of the study was to investigate whether females with symptomatic OTCD rely on alternative pathways to compensate for the reduced urea synthesis activity observed in this disorder. Design: The 5-d study involved 6 control subjects (3 males, 3 females) and 6 female OTCD carriers who had a fixed energy intake of 133 kJ · kg1 · d1 and a protein intake of 0.8 g · kg1 · d1. They underwent two 12-h periods of isotopic tracer administration, separated by 2 d. On both occasions, [18O] or [13C]urea was infused intravenously, and the subjects consumed hourly meals. During the first period, [15N]NH4Cl was given intravenously; during the second period, the tracer was given as hourly oral doses. Results: OTCD carriers produced less urea (P < 0.05) but had a higher (P < 0.05) mean ammonia appearance rate and plasma ammonia concentration than did control subjects. OTCD carriers incorporated a lower (P < 0.001) mean (± SE) proportion of the intravenous [15N]NH4Cl dose into circulating urea than did control subjects (16 ± 1% compared with 36 ± 2%), but there was no genotypic difference in the incorporation of orally administered tracer (81 ± 4% compared with 72 ± 4%, respectively). Conclusion: A good degree of dietary protein tolerance seemed to be retained in OTCD carriers by the maintenance of higher ammonia appearance rates, expansion of the plasma ammonia pool, and reliance on the ability of the perivenous hepatocytes to clear excess ammonia via glutamine synthesis. [ABSTRACT FROM AUTHOR]

The article offers a study of the changes in the metabolism of ammonia in freshwater teleost (Clarias batrachus) exposed to the organo phosphate compound (OP) trichlorfon. It says that there is a decrease in the tissue protein fractions, suggesting the use of protein during OP toxicity. It adds that there is an increased activities of several enzymes, including glutamate dehydrogenase, adenosine deaminases, and glutaminase, in liver, brain, and gill tissues.

Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fiber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes. [ABSTRACT FROM AUTHOR]

The author reflects on a study published by the journal on the potential of elevated concentrations of blood ammonia to cause hepatic dysfunction. He states that the study's conclusion that hyperammonaemia impairs the liver resulting to hepatic damage and hepatocyte apoptosis is intriguing due to the lack of evidence to support such observation. The need for further investigations on the involvement of ammonia toxicity in the pathogenesis of extrahepatic organ dysfunction is suggested.

A letter to the editor is presented in response to an article related to evaluation of storage stability of ammonia concentration in plasma by Peter Schuff-Werner and Steiner M. that was published in the previous issue.

IHA is characterized by a sudden increase in plasma ammonia levels in the absence of any identifiable causes, which mostly results in intractable coma and high mortality. It has been reported in some patients after receiving intensive chemotherapy for hematological malignancy or HSCT. We describe a case of a patient with FA that developed acute idiopathic hyperammonemia after the preparative regimen for HSCT. [ABSTRACT FROM AUTHOR]

Human carbamoyl phosphate synthetase (CPS1), a 1500-residue multidomain enzyme, catalyzes the first step of ammonia detoxification to urea requiring N-acetyl-L-glutamate (NAG) as essential activator to prevent ammonia/amino acids depletion. Here we present the crystal structures of CPS1 in the absence and in the presence of NAG, clarifying the on/off-switching of the urea cycle by NAG. By binding at the C-terminal domain of CPS1, NAG triggers long-range conformational changes affecting the two distant phosphorylation domains. These changes, concerted with the binding of nucleotides, result in a dramatic remodeling that stabilizes the catalytically competent conformation and the building of the ~35 Å-long tunnel that allows migration of the carbamate intermediate from its site of formation to the second phosphorylation site, where carbamoyl phosphate is produced. These structures allow rationalizing the effects of mutations found in patients with CPS1 deficiency (presenting hyperammonemia, mental retardation and even death), as exemplified here for some mutations. [ABSTRACT FROM AUTHOR]

The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. [ABSTRACT FROM AUTHOR]

McArdle’s disease is characterized by deficiency of enzyme myophosphorylase that disrupts the mechanism of glycogen breakdown in skeletal muscle. In McArdle patients, during physical activities, little or no lactate is released in the skeletal muscle but level of ammonia gets excessively increased. Production of ammonia is catalysed by AMP deaminase (AMPD) and Adenylate kinase (AK). We measured the activities of AMPD and AK in 11 molecular genetically confirmed McArdle patients and compared with the respective activities of 27 healthy controls. AMPD deficiency is commonly found to be associated with a stop mutation p.Q12X in AMPD1 gene. Therefore, all McArdle patients and controls were screened for this mutation. The p.Q12X stop mutation was identified heterozygote in 2 patients and 7 controls. The AMPD activities in patients and controls that did not harbour this mutation were significantly higher than in respective heterozygote patients and controls. However, there was no significant difference in the AMPD activities between patients and controls. The activities of AK were also not significantly different in patients and controls ( p = 0.644). Present study shows that the high ammonia production in McArdle patients is not based on enzyme induction of AMPD and AK but derives from other mechanisms (such as increased enzyme catalytic reaction, stimulated by for instance a highly concentrated ADP, or from alternative pathways of the muscle (like the protein metabolism). [ABSTRACT FROM AUTHOR]