Neurotoxicity of Ammonia

Oja, Simo S.; Saransaari, Pirjo; Korpi, Esa R.

doi:10.1007/s11064-016-2014-x

Cited by 66 publications

(60 citation statements)

References 104 publications

(106 reference statements)

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“…The oxidative deamination of amino acids generates toxic ammonium (NH 3 , NH 4 + ), which can cause immunosuppression and neurotoxic effects 68, 69 . In a normal state, giant African snails mainly convert ammonium into uric acid and excrete it out of their body through the urine, while during aestivation, they convert ammonium into urea and store it in their body 24, 70 .…”

Section: Resultsmentioning

confidence: 99%

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition

Liu

Ren

et al. 2020

Preprint

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Whole-genome duplication (WGD) has been observed across a wide variety of eukaryotic groups, contributing to evolutionary diversity and environmental adaptability. Mollusks are the second largest group of animals, and are among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition, and no comprehensive research on WGD has been reported in this group. To explore WGD and the A-T transition in Mollusca, we assembled a chromosome-level reference genome for the giant African snail Achatina immaculata, a global invasive species, and compared the genomes of two giant African snails (A. immaculata and Achatina fulica) to the other available mollusk genomes. The chromosome-level macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested the occurrence of a WGD event shared by A. immaculata and A. fulica. The estimated timing of this WGD event (∼70 MYA) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD reported herein may have been a common event shared by all Sigmurethra-Orthurethra species and could have conferred ecological adaptability and genomic plasticity allowing the survival of the K-T extinction. Based on macrosynteny, we deduced an ancestral karyotype containing 8 conserved clusters for the Gastropoda-Bivalvia lineage. To reveal the mechanism of WGD in shaping adaptability to terrestrial ecosystems, we investigated gene families related to the respiration, aestivation and immune defense of giant African snails. Several mucus-related gene families expanded early in the Stylommatophora lineage, functioning in water retention, immune defense and wound healing. The hemocyanins, PCK and FBP families were doubled and retained after WGD, enhancing the capacity for gas exchange and glucose homeostasis in aestivation. After the WGD, zinc metalloproteinase genes were highly tandemly duplicated to protect tissue against ROS damage. This evidence collectively suggests that although the WGD may not have been the direct driver of the A-T transition, it provided an important legacy for the terrestrial adaptation of the giant African snail.

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Section: Resultsmentioning

confidence: 99%

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition

Liu

Ren

et al. 2020

Preprint

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“…Ammonia is cleared mainly through conversion to urea (by the urea cycle consisting of five enzymatic steps) in the liver . Elevated concentrations of ammonia lead to the symptoms of ammonia intoxication (e.g., tremors, vomiting, and cerebral edema), coma, and even death . A number of serious diseases such as phenylketonuria, homocystinuria, and albinism can be traced to genetic defects in the enzymes of amino acid metabolism .…”

mentioning

confidence: 99%

Reverse Erythroblastosis Virus α Antagonism Promotes Homocysteine Catabolism and Ammonia Clearance

et al. 2019

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Metabolic homeostasis of amino acids is essential for human health. Here, we aimed to investigate a potential role for the clock component reverse erythroblastosis virus α (Rev‐erbα) in circadian regulation of amino acid metabolism. RNA‐seq with Rev‐erbα‐/‐ mice showed expression changes in genes involved in amino acid metabolism, particularly, the urea cycle and methionine metabolism. Rev‐erbα ablation increased hepatic mRNA, protein, and enzymatic activity of betaine homocysteine methyltransferase (Bhmt), cystathionine β‐synthase (Cbs), and cystathionine γ‐lyase (Cth) and decreased the levels of plasma and liver homocysteine in mice. Cell‐based assays confirmed negative regulation of these three genes by Rev‐erbα. Combined luciferase reporter, mobility‐shift, and chromatin immunoprecipitation assays identified Rev‐erbα as a transcriptional repressor of Bhmt, Cbs, and Cth. Rev‐erbα ablation or antagonism alleviated chemical‐induced hyperhomocysteinemia in mice. This was accompanied by elevated expressions of Bhmt, Cbs, and Cth. Moreover, Rev‐erbα ablation or antagonism promoted urea production and ammonia clearance. Of urea cycle–related genes, arginase 1 (Arg1), ornithine transcarbamylase (Otc), and carbamoyl‐phosphate synthase 1 (Cps1) expressions were up‐regulated in Rev‐erbα‐/‐ mice. Negative regulation of these urea cycle genes by Rev‐erbα was validated using cell‐based experiments. Mechanistic studies revealed that Rev‐erbα inhibited CCAAT‐enhancer‐binding protein α transactivation to repress the transcription of Arg1, Cps1, and Otc. Conclusion: Rev‐erbα antagonism alleviates hyperhomocysteinemia and promotes ammonia clearance. Targeting Rev‐erbα represents an approach for the management of homocysteine‐ and ammonia‐related diseases.

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“…Ammonia is a neurotoxic substance produced in the body through the metabolism of proteins and amino acids as well as by the actions of intestinal bacteria 3. Under normal conditions, the majority of this ammonia is converted in the liver to the water soluble substance urea via the urea cycle 4.…”

Section: Discussionmentioning

confidence: 99%

Multifactorial non-cirrhotic hyperammonaemic encephalopathy

2018

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A 51-year-old female presented with acute confusion associated with a non-specific headache and lethargy. The patient's history included bipolar disorder on valproate and recent travel to northern Vietnam. The patient was subsequently found to have hyperammonaemia as well as a urinary tract infection and bacteraemia with The patient was presumed to have a multifactorial non-cirrhotic hyperammonaemic encephalopathy due to a combination of a urinary tract infection and bacteraemia with, a urease-producing bacteria, and also valproate use, a medication known to interfere with ammonia elimination. The patient's treatment included supportive care, ceasing valproate, empiric then rationalised antibiotics, N-acetylcysteine and L-carnitine. We present a case of non-cirrhotic hyperammonaemic encephalopathy and explain why it is multifactorial in origin.

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Neurotoxicity of Ammonia

Cited by 66 publications

References 104 publications

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition

Reverse Erythroblastosis Virus α Antagonism Promotes Homocysteine Catabolism and Ammonia Clearance

Multifactorial non-cirrhotic hyperammonaemic encephalopathy

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