Methionine biosynthesis in normal and transformed fibroblasts

Kamely, Daphne; Weissbach, Herbert; Kerwar, S.S.

doi:10.1016/0003-9861(77)90084-4

Cited by 18 publications

(6 citation statements)

References 10 publications

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“…This enzyme is deficient in many other malignant cells ( [75,128,129], and references cited therein) and the deficiency is usually correlated with a requirement in vitro for cystine [129] or a source of sulphane sulphur [74]. Virus-induced malignant transformation of both human and murine cells has been shown to be associated with changes in sulphur metabolism, including deficiency of cystathionase [69], inability to use homocysteine in place of cystine [69], and induction of methionine auxotrophy [130,131].…”

Section: Altered Sulphur Metabolism Associated With Cellular Processesmentioning

confidence: 99%

Sulphane sulphur in biological systems: a possible regulatory role

Toohey¹

1989

Biochemical Journal

227

186

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cess appears to be essential for making the sulphur cyanolysable as evidenced by the acquisition of cyanolysability when ,-mercaptopyruvate is converted to the disulphide; only the latter can give the -S(S)form. This tautomerization can also occur in polysulphides and the lability of the sulphur in polysulphides with n > 3 compared with the stability of dialkyldisulphides (n = 2) again reflects the capacity to tautomerize

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Section: Altered Sulphur Metabolism Associated With Cellular Processesmentioning

confidence: 99%

Sulphane sulphur in biological systems: a possible regulatory role

Toohey¹

1989

Biochemical Journal

227

186

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“…The original suggestion (Ashe et al, 1974) for this lack of growth in homocysteine-supplemented medium was diminished in vivo activity of 5-methyltetrahydropteroyl -L -glutamate: L -homocysteine S-methyltransferase (EC 2.1.1.13) the enzyme which catalyses the terminal reaction in Met biosynthesis. However, in normal and SV40-transformed human fibroblasts, the latter of which show a growth requirement for Met, the activities of both 5,10-methylenetetrahydrofolate reductase and the transmethylase are similar (Kamely et al, 1977). Furthermore, 2 revertant SV40-transformed cell lines regained the ability to grow in homocysteine-supplemented medium without any substantial changes in homocysteine transmethylase, 5,10-methylenetetrahydrofolate reductase, or in their ability to take up 5-methyltetrahydrofolate (Hoffman et al, 1978).…”

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confidence: 95%

Effect of methionine deprivation on methylation and synthesis of macromolecules

Tisdale¹

1980

Br J Cancer

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Summary.-The growth of 4 tumour-cell lines (Walker rat mammary carcinoma (W-256), a mouse lymphoma (TLX5), a mouse bladder carcinoma (MB) and a human bladder carcinoma (EJ)) was much reduced when methionine in the culture medium was substituted by homocysteine. In contrast, a human embryonic fibroblast line grew equally well under such conditions. Although homocysteine alone was unable to support growth of W-256 it stimulated growth at low methionine concentrations.When W-256 was cultured for 24 h in medium containing homocysteine only, the extent of methylation of nucleic acids and the acid-soluble pool of methionine were decreased. However, under such conditions there was an increased methylase activity towards both endogenous substrate and E. coli tRNA. The effect of methionine removal was to cause a large increase in the Vmax value for methylation of tRNA, without any change in the Km value towards S-adenosyl-L-methionine (SAM). For both W-256 and TLX5, methionine deprivation caused a rapid inhibition of RNA biosynthesis, followed by inhibition of DNA synthesis, while protein synthesis tended to increase. This suggests that the inability of W-256 and TLX5 to survive and grow in methionine-deficient, homocysteine-supplemented medium is not due to insufficient methionine for protein biosynthesis, but may be related to an enhanced methylating activity of some tumour-cell lines.

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“…F o r example, N -5methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13), which, in the presence of vitamin B-12, synthesizes methionine from hornocysteine, is present in transformed fibroblasts but is inactive (Kamely et al, 1977). Transformed fibroblasts require methionine (and are unable to use homocysteine) from the medium for growth (Kamely et al, 1977). Similarly, it is possible that folate-utilizing enzymes in brain are normally inactive and that products of these enzymes enter the brain exclusively from the blood (Reynolds, 1976).…”

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confidence: 99%

Methionine Recycling in Brain: A Role for Folates and Vitamin B‐12

Spector

Coakley

Blakely

1980

Journal of Neurochemistry

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The recycling of methionine via homocysteine was measured in vivo in brain. After constant intravenous infusions (5 h) of both [3H-methyl]methionine and [35S]methionine into rats, the ratios of [3H-methyl]methionine to [35S]methionine in liver, brain, and plasma were determined. Similar experiments were performed in rabbits, except that the [3H-methyl]- and [35S]methionine were injected intraventricularly. If the methyl group of methionine was removed with the formation of homocysteine and then replaced by another (unlabeled) methyl group, the specific activity of the [3H-methyl]methionine would decrease more than that of [35S]methionine; i.e., the ratio of [3H-methyl]- to [35S]methionine in the tissue would decline. The results showed that the ratios of [3H-methyl]- to [35S]methionine in liver and brain were less than the same ratio in plasma in the rats. The comparable ratios in the brain and CSF of rabbits were less than the ratio in the injectate. Since brain contains only one enzyme capable of remethylating homocysteine to methionine, the vitamin B-12-dependent methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13), our results for methionine recycling via homocysteine in brain strongly support the activity of this enzyme in brain in vivo.

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Methionine biosynthesis in normal and transformed fibroblasts

Cited by 18 publications

References 10 publications

Sulphane sulphur in biological systems: a possible regulatory role

Sulphane sulphur in biological systems: a possible regulatory role

Effect of methionine deprivation on methylation and synthesis of macromolecules

Methionine Recycling in Brain: A Role for Folates and Vitamin B‐12

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