Macrophages and methylthio groups in lymphocyte proliferation

Toohey, John I.

doi:10.1002/jsscb.380170103

Cited by 13 publications

(16 citation statements)

References 51 publications

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“…Sera other than fetal calf serum are ineffective with the second group [18]. Cystine is active at 1 mM in the presence of a pyridoxal catalyst [17].…”

Section: Sulfur As a Regulatory Agentmentioning

confidence: 99%

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Toohey¹,

2014

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The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0) sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, iron-sulfur clusters), sulfuration of tRNA, modulation of enzyme activities, and regulating the redox environment by several mechanisms (including the enhancement of the reductive capacity of glutathione). A brief review of the analogous form of selenium suggests that the toxicity of selenium may be due to over-reduction caused by the powerful reductive activity of glutathione perselenide.

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“…Sera other than fetal calf serum are ineffective with the second group [18]. Cystine is active at 1 mM in the presence of a pyridoxal catalyst [17].…”

Section: Sulfur As a Regulatory Agentmentioning

confidence: 99%

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Toohey¹,

2014

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“…In the first, it is a byproduct of polyamine synthesis (36), which also yields methylthioadenosine. This may be cleaved to methylthioribose 1-phosphate and adenine by a specific nucleoside phosphorylase (37 (44,(46)(47)(48), by certain disulfides (42), by CH3S-group donors (49), and by feeder cells (46,50). In the presence of sulfhydryl compounds, horse, bovine, calf, and newborn calf sera cannot replace fetal calf serum, and growth factor activity in the latter is lost after dialysis against glutathione (50).…”

Section: Resultsmentioning

confidence: 99%

“…This may be cleaved to methylthioribose 1-phosphate and adenine by a specific nucleoside phosphorylase (37 (44,(46)(47)(48), by certain disulfides (42), by CH3S-group donors (49), and by feeder cells (46,50). In the presence of sulfhydryl compounds, horse, bovine, calf, and newborn calf sera cannot replace fetal calf serum, and growth factor activity in the latter is lost after dialysis against glutathione (50). CH3S groups have been demonstrated in fetal calf serum protein, suggesting that these could be its uniquely stable growth factor (50).…”

Section: Resultsmentioning

confidence: 99%

“…In the presence of sulfhydryl compounds, horse, bovine, calf, and newborn calf sera cannot replace fetal calf serum, and growth factor activity in the latter is lost after dialysis against glutathione (50). CH3S groups have been demonstrated in fetal calf serum protein, suggesting that these could be its uniquely stable growth factor (50). Further, L1210 cells are completely lacking in methylthioadenosine phosphorylase (37) and markedly deficient in cystathionase (51), crucial enzymes in metabolic pathways potentially leading to generation of CH3S groups or persulfides.…”

Section: Resultsmentioning

confidence: 99%

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Modification of erythrocyte enzyme activities by persulfides and methanethiol: possible regulatory role.

Valentine¹,

Toohey²,

Paglia³

et al. 1987

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

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Sulfhydryl modification of 22 human erythrocyte enzymes was achieved by exposing intact erythrocytes, hemolysates, and partially purified enzymes to (i) persulfides (RSSH) generated nonenzymatically from cystine in the presence of pyridoxal phosphate and (ii) mercaptopyruvate, which donates its sulfur to suitable acceptors with the mediation of the carrier enzyme, mercaptopyruvate sulfurtransferase (EC 2.8.1.2). The inhibition pattern was qualitatively similar for persulfides and that previously reported by us for the methylthio-group donor, methyl methanethiosulfonate. Thirteen activities were inhibited, and 9 were minimally or not at all affected. Pyruvate kinase was similarly modified by all systems in terms of phosphoenolpyruvate kinetics, thermostability, and interaction with the negative effector ATP. Partial-to-complete reversal of inhibition was documented in a subset of activities inhibited by mercaptopyruvate upon 30-min incubation with 1 mM dithiothreitol. A possible physiologic role for methylthio groups and for persulfides is discussed.In previous studies (1, 2) we have reported the effects of methyl methanethiosulfonate, CH3SO2SCH3, a CH3S donor developed by Smith et al. (3), on certain erythrocyte enzymes. CH3SO2SCH3 is one of a family of alkyl alkanethiosulfonates and delivers its CH3S group under mild conditions to accessible cysteinyl residues of enzyme proteins. It readily traverses the erythrocyte (RBC) membrane and produces profound alterations in certain enzyme properties, including catalytic activity and thermostability (1, 2).Persulfides are intermediates in sulfur compound transformations in which -SH is bonded to another sulfur atom to form RSSH. Accumulating evidence of a potential physiological role for persulfide sulfur in biological systems (partially reviewed in ref 4) prompted the present study comparing persuffide effects with those of CH3SO2SCH3 on RBC enzymes. Since low molecular weight persulfides are unstable near pH 7, it was necessary to use incubation systems in which persulfide was continuously generated. The first of these was initially described by Cavallini et al. (5), who showed that pyridoxal with a metal causes the P-elimination reaction of cystine, with the nonenzymatic formation of cysteine persulfide, ammonia, and pyruvate. The second incubation system utilized mercaptopyruvate as the sulfur donor (4). This sulfhydryl compound is the substrate for sulfurtransferase (EC 2.8.1.2) (6), which accepts, transports, and transfers its sulfur to form persulfides with suitable acceptors. This enzyme is present in human RBC (7). METHODS RBC and Hemolysates. Blood treated with the anticoagulant heparin was washed and freed of leukocytes by passage with saline over a column of microcellulose (8). After washing, centrifugation, and resuspension in saline, the RBC were adjusted to =4-4.5 x 106 per A.l. Where indicated, cells were lysed as described in text.Partially Purified Lysates. Hemolysates were largely freed of Hb precipitated by ZnSO4 at pH 8.0 in 0.1 M Tris HCl ...

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“…This pathway can generate methylthio groups via ketomethylthiobutyrate (see Fig. The essential growth factor was, at first, provided by fetal calf serum plus a sulfhydryl compound [94]; later it was shown that treatment of fetal calf serum with R-SH caused the release of CH 3 -SH which was identified by GC-MS [95]. These findings sugggest that methylthio groups have an essential function in all cells.…”

Section: Teleology: Why Should Mthf:hmt Make Isomethionine?mentioning

confidence: 99%

Vitamin B₁₂and methionine synthesis: A critical review. Is nature's most beautiful cofactor misunderstood?

Toohey¹

2006

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The mechanism by which Vitamin B12 prevents demyelination of nerve tissue is still not known. The evidence indicates that the critical site of B12 function in nerve tissue is in the enzyme, methionine synthase, in a system which requires S-adenosylmethionine. In recent years it has been recognized that S-adenosylmethionine gives rise to the deoxyadenosyl radical which catalyzes many reactions including the rearrangement of lysine to beta-lysine. Evidence is reviewed which suggests that there is an analogy between the two systems and that S-adenosyl methionine may catalyze a rearrangement of homocysteine on methionine synthase giving rise to iso- or beta-methionine. The rearranged product is readily degraded to CH3-SH, providing a mechanism for removing toxic homocysteine.

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Macrophages and methylthio groups in lymphocyte proliferation

Cited by 13 publications

References 51 publications

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Modification of erythrocyte enzyme activities by persulfides and methanethiol: possible regulatory role.

Vitamin B₁₂and methionine synthesis: A critical review. Is nature's most beautiful cofactor misunderstood?

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Macrophages and methylthio groups in lymphocyte proliferation

Cited by 13 publications

References 51 publications

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Modification of erythrocyte enzyme activities by persulfides and methanethiol: possible regulatory role.

Vitamin B12and methionine synthesis: A critical review. Is nature's most beautiful cofactor misunderstood?

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Vitamin B₁₂and methionine synthesis: A critical review. Is nature's most beautiful cofactor misunderstood?