Nicotinamide methyltransferase and S-adenosylmethionine:5'-methylthioadenosine hydrolase. Control of transfer ribonucleic acid methylation

Swiatek, Kenneth R.; Simon, Lionel N.; Chao, K.

doi:10.1021/bi00747a019

Cited by 55 publications

(13 citation statements)

References 16 publications

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“…Several mechanisms have been proposed for the physiological regulation of tRNA methyltransferases.-These include stimulation of activity by cations such as polyamines (1), depletion of the S-adenosylmethionine (SAM) substrate by competing methyltransferases (2,3), and inhibition of tRNA methylating enzymes by elevated S-adenosylhomocysteine (SAH) levels (4)(5)(6)(7). All of these factors have been shown to affect the activity of crude tRNA methyltransferase preparations.…”

Section: Introductionmentioning

confidence: 99%

S-Adenosylhomocysteine inhibition of three purified tRNA methyltransferases from rat liver

1975

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Three tRNA methyltransferases from rat liver have been fractionated and purified greater than 100-fold. These enzymes have been examined for their sensitivity to inhibition by S-adenosylhomocysteine (SAH). The methyltransferase which forms m2-guanine in the region between the dihydrouridine loop and the acceptor stem of tRNA (m2-guanine methyltransferase I) is least sensitive to SAH inhibition, with a Ki of 8 PM. The enzyme responsible for forming m2guanine between the dihydrouridine and anticodon loops (m2-guanine methyltransferase II) has a Ki of 0.3 PM, while ml-adenine methyltransferase shows intermediate sensitivity to SAH (Ki = 2.4 "PM). All three methyltransferases have similar Km's for the S-adenosylmethionine substrate (1.5-2.0 PM). These results are consistent with the hypothesis that activity of individual tRNA methyltransferases may be controlled by enzyme systems which alter cellular SAH levels.

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Section: Introductionmentioning

confidence: 99%

S-Adenosylhomocysteine inhibition of three purified tRNA methyltransferases from rat liver

1975

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“…direct cleavage of S-adenosylmethionine into 5'-methylthioadenosine and a-amino-y-butyrolactone, through the action of a specific lyase (Shapiro & Mather, 1958;Pietropaolo et al, 1972;Swiatek et al, 1973), represents the first reaction leading to the formation of the thioether; probably the primary role of this reaction is the control of the cellular concentrations of S-adenosylmethionine. The other pathway, which is the most relevant quantitatively, involves the transfer of the propylamine moiety from the decarboxylated S-adenosylmethionine to putrescine or spermidine (Pegg& Williams-Ashman, 1970;Bowman et al, 1973;Tabor & Tabor, 1976;Zappia et al, 1977a): 2mol of 5'-methylthioadenosine is released/mol of spermine and 1 mol/mol of spermidine.…”

mentioning

confidence: 99%

Substrate specificity of 5′-methylthioadenosine phosphorylase from human prostate

Zappia¹,

Oliva²,

Cacciapuoti³

et al. 1978

Biochemical Journal

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5'-Methylthioadenosine phosphorylase was purified approx. 340-fold from human prostate by using affinity chromatography by Hg-coupled Sepharose. The enzyme, responsible for the breakdown of 5'-methylthioadenosine into adenine and methylthioribose 1-phosphate, was partially characterized. The apparent Km for 5'-methylthioadenosine is 25,uM. It is activated by thiols and shows an absolute requirement for phosphate ions. New analogues of 5'-methylthioadenosine were prepared and their activity as substrates or inhibitors of the reaction was investigated. The replacement of the 6-amino group of the adenine moiety by a hydroxy group, as well as the replacement of N-7 by a methinic radical, resulted in an almost complete loss ofactivity. Otherwise the replacement of sulphur by selenium, as well as that of the methyl group by an ethyl one, is compatible with the activity as substrate. The positively charged sulphonium group also prevents catalytic interaction with the enzyme. The inhibitory effect of 5'-methylthiotubercidin (competitive) and 5'-dimethylthioadenosine sulphonium salt (non-competitive) was also demonstrated. The reported results suggest three binding sites between the substrate and the enzyme.

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“…Methylthioadenosine is also formed by direct cleavage of homoserine lactone from S-adenosylmethionine in pig liver [50], but this is not considered to be a major pathway in most animal cells.…”

Section: Methylthio Group Generation From Methylthioadenosinementioning

confidence: 99%

Macrophages and methylthio groups in lymphocyte proliferation

Toohey

1981

J. Supramol. Struct. Cell. Biochem.

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Macrophages are shown to replace methylthio disulfides in supporting in vitro proliferation of three cell lines previously characterized as methylthio-dependent. Macrophages have the capacity to generate methylthio groups from methylthioadenosine. It is hypothesized that macrophages stimulate cell proliferation both in normal immune systems and in certain cancers by providing an abundance of methylthio groups. Fetal calf serum is shown to contain methylthio groups. It appears that, in cell cultures containing fetal calf serum, sulfhydryl compounds stimulate cell proliferation by making the methylthio groups in the serum available to the cells.

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Nicotinamide methyltransferase and S-adenosylmethionine:5'-methylthioadenosine hydrolase. Control of transfer ribonucleic acid methylation

Cited by 55 publications

References 16 publications

S-Adenosylhomocysteine inhibition of three purified tRNA methyltransferases from rat liver

S-Adenosylhomocysteine inhibition of three purified tRNA methyltransferases from rat liver

Substrate specificity of 5′-methylthioadenosine phosphorylase from human prostate

Macrophages and methylthio groups in lymphocyte proliferation

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