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Biomedical subjects

M A Foster

Publications and source records attributed to M A Foster.

At least 91 records · Page 5Linked to original sources

A study of electron spin resonance spectra of whole blood from normal and tumour bearing patients.

Electron spin resonance spectra have been obtained from samples of frozen whole blood or separated blood cells and plasma. Blood samples were obtained from human controls having no diagnosed malignancy and from patients with a variety of benign and malignant tumours.The characteristic spectrum from control blood shows two main lines with g values of 4·2 and 2·049. Several smaller lines can also be observed. The line at g = 2·049 may be due to the copper protein ceruloplasmin. Although no qualitative differences could be found between the spectra from controls and cancer patients, samples from patients with certain types of tumour showed a significant increase in size of the g = 2·049 signal above control values. This was most noticeably the case with Hodgkin's disease and to a lesser extent with cancers of the breast. Squamous cell carcinomata, taken as a group, did not show an elevation in average size of the g = 2·049 signal. In this latter group, however, there were some indications that the effects of chemotherapeutic treatment could be followed during the early stages of such treatment. Examples are given in which onset of treatment with various cytotoxic agents was associated with reduction in size of the g = 2·049 signal.

Blood Cells↗

Folic acid and the methylation of homocysteine by Bacillus subtilis.

1. Cell-free extracts of Bacillus subtilis synthesize methionine from serine and homocysteine without added folate. The endogenous folate may be replaced by tetrahydropteroyltriglutamate or an extract of heated Escherichia coli for the overall C(1) transfer, but tetrahydropteroylmonoglutamate is relatively inactive. 2. Extracts of B. subtilis contain serine transhydroxymethylase and 5,10-methylenetetrahydrofolate reductase, which are non-specific with respect to the glutamate content of the folate substrates. Methyl transfer to homocysteine requires a polyglutamate folate as methyl donor. These properties are not affected by growth of the organism with added vitamin B(12). 3. The synthesis of methionine from 5-methyltetrahydropteroyltriglutamate and homocysteine has the characteristics of the cobalamin-independent reaction of E. coli. No evidence for a cobalamin-dependent transmethylation was obtained. 4. S-Adenosylmethionine was not a significant precursor of the methyl group of methionine with cell-free extracts, neither was S-adenosylmethionine generated by methylation of S-adenosylhomocysteine by 5-methyltetrahydrofolate. 5. A procedure for the isolation and analysis of folic acid derivatives from natural sources is described. 6. The folates isolated from lysozyme extracts of B. subtilis are sensitive to folic acid conjugase. One has been identified as 5-formyltetrahydropteroyltriglutamate; the other is possibly a diglutamate folate. 7. A sequence is proposed for methionine biosynthesis in B. subtilis in which methyl groups are generated from serine and transferred to homocysteine by means of a cobalamin-independent pathway mediated by conjugated folate coenzymes.

Alcohol Oxidoreductases↗

The microbial biosynthesis of methionine.

1. The enzymes leading to the methylation of homocysteine have been examined in three micro-organisms: a cobalamin-producing bacterium, Bacillus megaterium; a yeast, Candida utilis; and a basidiomycete fungus, Coprinus lagopus. The yeast and the fungus contain negligible endogenous cobalamin. 2. Extracts of each organism catalyse C(1)-transfer from serine to homocysteine with a polyglutamate folate coenzyme. 3. The enzymes generating the methyl group of methionine from C-3 of serine have similar properties in each case, but different mechanisms of homocysteine transmethylation from 5-methyltetrahydrofolates were found. 4. B. megaterium contains an enzyme with properties suggestive of a vitamin B(12)-dependent homocysteine transmethylase, whereas Cand. utilis and Cop. lagopus transfer the methyl group by a reaction characteristic of the cobalamin-independent mechanism established for Escherichia coli. 5. The specificity of each transmethylase for a 5-methyltetrahydropteroylpolyglutamate is consistent with the results of analyses of endogenous folates in these organisms, which showed only conjugated forms. 6. None of the extracts catalysed methionine production from S-adenosylmethionine and homocysteine. 7. These results are compared with results now available for methionine synthesis in other organisms, which show a considerable diversity of mechanisms.

Bacillus megaterium↗

Methionine synthesis by extracts of Salmonella typhimurium.

1. Following the genetic studies by Smith (1961) and Smith & Childs (1963) with methionine auxotrophs of Salmonella typhimurium, methionine formation from homocysteine has been investigated with cell-free extracts of this organism. 2. As found with Escherichia coli (Woods, Foster & Guest, 1964), methyl groups are formed by an N(5)N(10)-methylenetetrahydrofolate reductase. They are then transferred to homocysteine by either a simple N(5)-methyltetrahydropteroyl-triglutamate-homocysteine methyltransferase or alternatively a cobalamin-dependent N(5)-methyltetrahydrofolate-homocysteine methyltransferase. 3. S. typhimurium differs from E. coli in being able to synthesize significant amounts of cobalamin.

Alcohol Oxidoreductases↗