S-Adenosylmethionine: The Relation of Configuration at the Sulfonium Center to Enzymatic Reactivity<sup>1</sup>

Haba, G. de la; Jamieson, Gordon A.; Mudd, S. Harvey; Richards, Henry H.

doi:10.1021/ja01524a039

Cited by 93 publications

(46 citation statements)

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“…All three A. thaliana HMT enzymes use (S,S)-S-adenosylmethionine as a methyl group donor much less efficiently than S-methylmethionine (Ranocha et al, 2000;Ranocha et al, 2001). However, in natural systems, biologically active (S,S)-S-adenosylmethionine can spontaneously racemize at the sulfonium ion to form toxic (R,S)-S-adenosylmethionine (de la Haba et al, 1959), which is removed via a salvage pathway. Recent evidence of homocysteine methyltransferase activity specific for (R,S)-S-adenosylmethionine in A. thaliana (Vinci and Clarke, 2007) suggests that one or more of the three A. thaliana HMT enzymes may catalyze this reaction.…”

Section: The S-methylmethionine Cyclementioning

confidence: 99%

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Jander

Joshi

2009

The Arabidopsis Book

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The aspartate-derived amino acid pathway in plants leads to the biosynthesis of lysine, methionine, threonine, and isoleucine. These four amino acids are essential in the diets of humans and other animals, but are present in growthlimiting quantities in some of the world's major food crops. Genetic and biochemical approaches have been used for the functional analysis of almost all Arabidopsis thaliana enzymes involved in aspartate-derived amino acid biosynthesis. The branch-point enzymes aspartate kinase, dihydrodipicolinate synthase, homoserine dehydrogenase, cystathionine gamma synthase, threonine synthase, and threonine deaminase contain well-studied sites for allosteric regulation by pathway products and other plant metabolites. In contrast, relatively little is known about the transcriptional regulation of amino acid biosynthesis and the mechanisms that are used to balance aspartatederived amino acid biosynthesis with other plant metabolic needs. The aspartate-derived amino acid pathway provides excellent examples of basic research conducted with A. thaliana that has been used to improve the nutritional quality of crop plants, in particular to increase the accumulation of lysine in maize and methionine in potatoes.

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Section: The S-methylmethionine Cyclementioning

confidence: 99%

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Jander

Joshi

2009

The Arabidopsis Book

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“…Altered transcription of two other genes that may also contribute to the increase in Hcy was also found in the SV of Cx30 Ϫ/Ϫ mice. Thus, Sahh, which encodes S-adenosyl Hcy hydrolase, an enzyme involved in Hcy synthesis from methionine (30), was up-regulated 1.4-fold over control values, whereas Gsto1, which encodes the GST omega 1, a thiol-transferase that may metabolize Hcy (31), was down-regulated 2.2-fold under control levels. The expression of other genes encoding enzymes for the remethylation and transsulfuration pathways of Hcy (29) was unaffected.…”

Section: The Sv Electrogenic Machinery and The Marginal And Basal Cellmentioning

confidence: 99%

Connexin30 deficiency causes instrastrial fluid–blood barrier disruption within the cochlear stria vascularis

Cohen-Salmon

Regnault²,

Cayet

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

151

148

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The endocochlear potential (EP) is essential to hearing, because it provides approximately half of the driving force for the mechanoelectrical transduction current in auditory hair cells. The EP is produced by the stria vascularis (SV), a vascularized bilayer epithelium of the cochlea lateral wall. The absence of the gap junction protein connexin30 (Cx30) in Cx30 ؊/؊ mice results in the SV failure to produce an EP, which mainly accounts for the severe congenital hearing impairment of these mice. Here, we show that the SV components of the EP electrogenic machinery and the epithelial barriers limiting the intrastrial fluid space, which are both necessary for the EP production, were preserved in Cx30 ؊/؊ mice. In contrast, the endothelial barrier of the capillaries supplying the SV was disrupted before EP onset. This disruption is expected to result in an intrastrial electric shunt that is sufficient to account for the absence of the EP production.

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“…1), is a strong inhibitor of transmethylation (1). The inhibition is relieved in prokaryotes by hydrolysis of SAH to adenine and ribosylhomocysteine (2), and in eukaryotes by hydrolysis of SAH to adenosine and homocysteine, catalyzed by SAH hydrolase (SAHH) (3). Because hydrolysis of SAH is reversible, and more favored in the synthetic direction, efficient transmethylation from SAM in eukaryotes also requires removal of adenosine and homocysteine (Fig.…”

mentioning

confidence: 99%

S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration

Shu

Mahadeo

Liu

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Chemotaxis of bacteria requires regulated methylation of chemoreceptors. However, despite considerable effort in the 1980s, transmethylation has never been established as a component of eukaryotic cell chemotaxis. S-adenosylhomocysteine (SAH), the product formed when the methyl group of the universal donor S-adenosylmethionine (SAM) is transferred to an acceptor molecule, is a potent inhibitor of all transmethylation reactions. In eukaryotic cells, this inhibition is relieved by hydrolysis of SAH to adenosine and homocysteine catalyzed by SAH hydrolase (SAHH). We now report that SAHH, which is diffuse in the cytoplasm of nonmotile Dictyostelium amoebae and human neutrophils, concentrates with F-actin in pseudopods at the front of motile, chemotaxing cells, but is not present in filopodia or at the very leading edge. Tubercidin, an inhibitor of SAHH, inhibits both chemotaxis and chemotaxis-dependent cell streaming of Dictyostelium, and chemotaxis of neutrophils at concentrations that have little effect on cell viability. Tubercidin does not inhibit starvationinduced expression of the cAMP receptor, cAR1, or G proteinmediated stimulation of adenylyl cyclase activity and actin polymerization in Dictyostelium. Tubercidin has no effect on either capping of Con A receptors or phagocytosis in Dictyostelium. These results add SAHH to the list of proteins that redistribute in response to chemotactic signals in Dictyostelium and neutrophils and strongly suggest a role for transmethylation in chemotaxis of eukaryotic cells.chemotaxis ͉ Dictyostelium ͉ neutrophils ͉ tubercidin S -adenosylhomocysteine (SAH), the product of the transfer of the methyl group from S-adenosylmethionine (SAM) to DNA, RNA, phospholipids and many small molecules ( Fig. 1), is a strong inhibitor of transmethylation (1). The inhibition is relieved in prokaryotes by hydrolysis of SAH to adenine and ribosylhomocysteine (2), and in eukaryotes by hydrolysis of SAH to adenosine and homocysteine, catalyzed by SAH hydrolase (SAHH) (3). Because hydrolysis of SAH is reversible, and more favored in the synthetic direction, efficient transmethylation from SAM in eukaryotes also requires removal of adenosine and homocysteine (Fig. 1).Stimulated by the discovery in the mid-1970s that bacterial chemotaxis is initiated by SAM-dependent transient carboxyl-O-methylation of glutamic acid residues in chemotactic ligand receptor proteins (4, 5), the possibility that transmethylation reactions have a role in the chemotactic response of Dictyostelium and leukocytes was investigated in the early 1980s. Investigators asked whether chemotactic factors increase methylation of proteins, phospholipids, and/or nucleic acids, and whether inhibition of methylation by inhibiting SAHH or adenosine deaminase inhibits chemotaxis. The results of these studies were inconclusive and often contradictory (see Discussion).In the contemporary view of chemotaxis of Dictyostelium and leukocytes, chemoattractants mediate their effects by binding to transmembrane receptors coupled to heterotrimer...

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S-Adenosylmethionine: The Relation of Configuration at the Sulfonium Center to Enzymatic Reactivity¹

Cited by 93 publications

References 1 publication

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Connexin30 deficiency causes instrastrial fluid–blood barrier disruption within the cochlear stria vascularis

S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration

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S-Adenosylmethionine: The Relation of Configuration at the Sulfonium Center to Enzymatic Reactivity1

Cited by 93 publications

References 1 publication

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

Connexin30 deficiency causes instrastrial fluid–blood barrier disruption within the cochlear stria vascularis

S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration

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S-Adenosylmethionine: The Relation of Configuration at the Sulfonium Center to Enzymatic Reactivity¹