S-adenosylmethionine synthesis: Molecular mechanisms and clinical implications

Mato, José M.; Álvarez, Luis; Ortiz, Pablo; Pajares, Marı́a A.

doi:10.1016/s0163-7258(96)00197-0

Cited by 453 publications

(500 citation statements)

References 131 publications

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“…1A) is consistent with hypomethylation of MAT1A in this tissue. These bands were absent in kidney, heart or spleen samples, tissues in which the MAT1A gene is silenced as previously reported [2] and as can be observed in the Northern blot shown in the lower panel of Fig. 1A.…”

Section: Resultssupporting

confidence: 88%

“…AdoMet is the major methyl group donor in transmethylation reactions and serves as the propylamino source in the biosynthesis of polyamines [2]. In mammals, this essential enzyme is the product of two di erent genes, MAT1A and MAT2A, which display a distinct pattern of expression among di erent tissues [2,3]. MAT1A is the predominant enzyme in liver parenchymal cells, while MAT2A is expressed in all other tissues, in the fetal liver and replaces MAT1A in hepatocarcinoma cells [4±6].…”

Section: Introductionmentioning

confidence: 99%

“…MAT1A is the predominant enzyme in liver parenchymal cells, while MAT2A is expressed in all other tissues, in the fetal liver and replaces MAT1A in hepatocarcinoma cells [4±6]. The existence of a liver-speci®c enzyme can be explained from a kinetic and regulatory perspective by the main role played by this organ in dietary methionine metabolism, a function for which the product of MAT1A is better suited [2,4,7].…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Torres

López-Rodas

Latasa

et al. 2000

The International Journal of Biochemistry & Cell Biology

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Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet). In mammals MAT activity derives from two separate genes which display a tissue-speci®c pattern of expression. While MAT1A is expressed only in the adult liver, MAT2A is expressed in non-hepatic tissues. The mechanisms behind the selective expression of these two genes are not fully understood. In the present report we have evaluated MAT1A and MAT2A methylation in liver and in other tissues, such as kidney, by methylationsensitive restriction enzyme digestion of genomic DNA. Our data indicate that MAT1A is hypomethylated in liver and hypermethylated in non-expressing tissues. The opposite situation is found for MAT2A. Additionally, histones associated to MAT1A and MAT2A genes showed enhanced levels of acetylation in expressing tissues (two-fold for MAT1A and 3.5-fold for MAT2A liver and kidney respectively). These observations support a role for chromatin structure and its modi®cation in the tissue-speci®c expression of both MAT genes. #

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Torres

López-Rodas

Latasa

et al. 2000

The International Journal of Biochemistry & Cell Biology

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“…One key metabolite of the methionine metabolic pathway is S-adenosylmethionine (SAM), which is the main methyl donor for biological reactions and serves as a precursor in glutathione and polyamine synthesis [175].…”

Section: Are Antioxidants Feasible Treatments For Fatty Liver Disease?mentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Mantena

King

Andringa

et al. 2008

Free Radical Biology and Medicine

388

302

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Fatty liver disease associated with chronic alcohol consumption or obesity/type 2 diabetes has emerged as a serious public health problem. Steatosis, accumulation of triglyceride in hepatocytes, is now recognized as a critical "first-hit" in the pathogenesis of liver disease. It is proposed that steatosis "primes" the liver to progress to more severe liver pathologies when individuals are exposed to subsequent metabolic and/or environmental stressors or "second-hits". Genetic risk factors can also influence the susceptibility and severity of fatty liver disease. Furthermore, oxidative stress, disrupted nitric oxide (NO) signaling, and mitochondrial dysfunctional are proposed to be key molecular events that accelerate or worsen steatosis and initiate progression to steatohepatitis and fibrosis. This review article will discuss the following topics regarding the pathobiology and molecular mechanisms responsible for fatty liver disease: 1) the "two-hit" or "multi-hit" hypothesis; 2) the role of mitochondrial bioenergetic defects and oxidant stress; 3) interplay between NO and mitochondria in fatty liver disease; 4) genetic risk factors and oxidative stress responsive genes; and 5) the feasibility of antioxidants for treatment.

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“…The first step in methionine metabolism is the formation of S-adenosylmethionine (SAM) catalyzed by methionine adenosyltransferase (MAT) (2,3). Under normal conditions, most of the 6-8 gm of SAM generated per day is used in transmethylation reaction in which methyl groups are added to compounds and SAM is converted to S-adenosylhomocysteine (SAH) (3,4). SAH is a potent competitive inhibitor of transmethylation reactions (3,5).…”

Section: Introductionmentioning

confidence: 99%

Effect of lecithin in the treatment of ethanol mediated free radical induced hepatotoxicity

Das

Vasudevan

2006

Indian J Clin Biochem

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Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Liver damage due to consumption of alcohol may be caused by oxygen radicals such as superoxide and hydroxyl radicals, generated during the metabolism of ethanol by the microsomal oxidizing system. Lecithin, an important class of phospholipids contains choline, which is considered as lipotropic factor. The effects of this lecithin as a hepatoprotective drug on body weight and antioxidant status of ethanol-exposed rats were studied. The results were compared with the effects of tocopheryl acetate. From the present study, it can be concluded that ethanol-induced stress can be partly prevented by tocopheryl acetate, and showed best result. Abstination from alcohol also involved for little hepatic regeneration. Supplementation of lecithin showed better effect compared to abstination from alcohol on reversing the effect of ethanol induced liver damage in the present study. Moreover, preventive measures were found to be better than curative treatment. Antioxidants are likely to provide beneficial effects on hepatocyes via desensitization against oxidant stress while inhibiting primary mechanism for expression of proinflammatory and cytotoxic mediators. However, abstinence from alcohol, proper nutrition, and supplementation of antioxidants, vitamins and hepatoprotective drugs are some of the therapeutic options.

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S-adenosylmethionine synthesis: Molecular mechanisms and clinical implications

Cited by 453 publications

References 131 publications

DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

DNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue-specific

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Effect of lecithin in the treatment of ethanol mediated free radical induced hepatotoxicity

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