Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders?

Barić, Ivo; Erdol, Sahin; Sağlam, Hilal; Lovrić, Mila; Belužić, Robert; Blom, Henk J.; Fumić, Ksenija

doi:10.1007/8904_2016_543

Cited by 11 publications

(4 citation statements)

References 21 publications

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“…This is a pathological condition caused by excessive consumption of Met, due to supplementation or a high protein diet, liver disease, premature birth, or can occur in case of an innate metabolism error, when Met is not properly metabolized [16]. Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by an impairment of enzymes such as Methionine adenosyltransferase (MAT) [17], glycine Nmethyltransferase (GNMT) [18], and S-adenosylhomocysteine hydrolase (AHCY) [19]. Despite that, hypermethioninemia can occur due to a secondary metabolic disorder like homocystinuria induced by cystathionine betasynthase (CBS) deficiency [20], tyrosinemia type I with mutations in the fumarylacetoacetate hydrolase (FAH) gene [21], and citrin deficiency [22].…”

Section: Introductionmentioning

confidence: 99%

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

et al. 2020

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Methionine (Met) has important functions for homeostasis of various species, including zebrafish. However, the increased levels of this amino acid in plasma, a condition known as hypermethioninemia, can lead to cell alterations. Met is crucial for the methylation process and its excesses interfere with the cell cycle, an effect that persists even after the removal of this amino acid. Some conditions may lead to a transient increase of this amino acid with unexplored persistent effects of Met exposure. In the present study, we investigated the behavioral and neurochemical effects after the withdrawal of Met exposure. Zebrafish were divided into two groups: control and Met-treated group (3 mM) for 7 days and after maintained for 8 days in tanks containing only water. In the eighth day post-exposure, we evaluated locomotion, anxiety, aggression, social interaction, and memory, as well as oxidative stress parameters, amino acid, and neurotransmitter levels in the zebrafish brain. Our results showed that 8 days after Met exposure, the treated group showed decreased locomotion and aggressive responses, as well as impaired aversive memory. The Met withdrawal did not change thiobarbituric acid reactive substances, reactive oxygen species, and nitrite levels; however, we observed a decrease in antioxidant enzymes superoxide dismutase, catalase, and total thiols. Epinephrine and cysteine levels were decreased after the Met withdrawal whereas carnitine and creatine levels were elevated. Our findings indicate that a transient increase in Met causes persistent neurotoxicity, observed by behavioral and cognitive changes after Met withdrawal and that the mechanisms underlying these effects are related to changes in antioxidant system, amino acid, and neurotransmitter levels.

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Section: Introductionmentioning

confidence: 99%

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

et al. 2020

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“…Conversion of sarcosine to glycine is performed by glycine N‐methyltransferase ( GNMT ). Deficiency has been described in four patients (MIM #606664) with hepatomegaly and elevated transaminases and seems to be less severe than a knock out mouse model also showing hepatic glycogen storage, hypercholesterinemia, hypoglycemia, and low white blood cell count …”

Section: The Role Of Choline As Methyl Donormentioning

confidence: 99%

Choline‐related‐inherited metabolic diseases—A mini review

Wortmann

Mayr

2019

J of Inher Metab Disea

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In humans, the important water soluble, vitamin‐like nutrient choline, is taken up with the diet or recycled in the liver. Deficiencies of choline have only been reported in experimental situations or total parenteral nutrition. Currently, no recommended dietary allowances are published; only an adequate daily intake is defined. Choline is involved in three main physiological processes: structural integrity and lipid‐derived signaling for cell membranes, cholinergic neurotransmission, and methylation. Choline is gaining increasing public attention due to studies reporting a relation of low choline levels to subclinical organ dysfunction (nonalcoholic fatty liver or muscle damage), stunting, and neural tube defects. Furthermore, positive effects on memory and a lowering of cardiovascular risks and inflammatory markers have been proposed. On the other hand, dietary choline has been associated with increased atherosclerosis in mice. This mini review will provide a summary of the biochemical pathways, in which choline is involved and their respective inborn errors of metabolism (caused by mutations in SLC5A7, CHAT, SLC44A1, CHKB, PCYT1A, CEPT1, CAD; DHODH, UMPS, FMO3, DMGDH, and GNMT). The broad phenotypic spectrum ranging from malodor, intellectual disability, to epilepsy, anemia, or congenital myasthenic syndrome is presented, highlighting the central role of choline within human metabolism.

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“…For example, it is down-regulated in almost all hepatocellular carcinoma (HCC) [ 35 ]; although abundantly expressed in the normal liver, GNMT expression is decreased in HCC tissues. GNMT deficiency is also associated with an inherited disorder of methionine metabolism [ 36 ]. Hepatic GNMT regulates lipid and glucose homeostasis, and its deficiency results in increased lipogenesis and triglycerides [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Liang

et al. 2018

Bioscience Reports

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Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.

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Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders?

Cited by 11 publications

References 21 publications

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

Withdrawal Effects Following Methionine Exposure in Adult Zebrafish

Choline‐related‐inherited metabolic diseases—A mini review

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

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