Biomedical subjects

S A Matlin

Publications and source records attributed to S A Matlin.

41 records · Page 3Linked to original sources

PubMed1976

Hepta- and hexa-carboxylic porphyrinogen intermediates in haem biosynthesis.

In the course of our studies on intermediates in normal and abnormal metabolism of porphyrins we have synthesised a number of porphyrins related to uroporphyrin-III and compared them with materials isolated from natural sources. In the present paper we show that the corresponding porphyrinogens are all metabolised to protoporphyrin-IX by haemolysates of chicken erythrocytes, but at different rates. The results are discussed in relation to our conclusions concerning the preferred pathway of degradation of uro'gen-III to coproporphyrinogen-III, which indicate a clockwise sequence of decarboxylation reactions.

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PubMed1976

Pentacarboxylic intermediates in haem biosynthesis.

The incorporation of the four possible type III porphyrinogens into protoporphyrin is described and their various rates or conversion are discussed. The techniques used involved the incubation of the porphyrinogens in chicken red cell haemolysates followed by extraction and characterisation of the end products on HPLC and TLC. Porphyrin 5 b c d was shown to be more slowly incorporated than porphyrins 5 a b d, 5 a c d and 5 a b c. The relevance of these findings to an understanding of the porphyrin excretion pattern in hepato-erythrocitic porphyria is considered.

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PubMed1975

Applications of high-pressure liquid chromatography and field desorption mass spectrometry in studies of natural porphyrins and chlorophyll derivatives.

Mixtures of porphyrins derived from natural sources can be readily separated by high-pressure liquid chromatography both analytically and on a preparative scale. A variety of procedures have been developed not only for the esters but also for free acids, and on the analytical scale quantitation is easily achieved by visible absorption. The retention times are largely characteristic of the number of carboxylic acid side chains (or other polar groups) but further information can be obtained by mass spectrometric studies of the various fractions. Field desorption mass spectrometry is particularly useful for this purpose because the emitter wire can be dipped directly into the eluates. The field desorption spectra of porphyrin free acids and esters as well as their metal complexes give essentially molecular ions with little or no fragmentation in most cases, whereas electron-impact mass spectrometry, particularly of free acids, is impeded by the low volatility of porphyrins. Mixtures can also be analysed by field desorption mass spectrometry, and this provides not only a rapid qualitative assessment of the components of a mixture, but also a check on the subsequent chromatographic separations.

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PubMedDate not supplied

Differential effects of (+) and (-) gossypol enantiomers on mitochondrial function and proliferation of cultured TM4 cells.

The in vitro effects of (+) and (-)gossypol enantiomers on the mitochondrial functions of mouse transformed Sertoli, TM4 cells were investigated by monitoring mitochondrial rhodamine 123 accumulation. When TM4 cells were cultured in medium without fetal calf serum, 5 micrograms/ml of both enantiomers caused similar declines in mitochondrial rhodamine 123 staining. By contrast, (-)gossypol had a greater adverse action than did (+)gossypol on the mitochondrial of TM4 cells that were cultured in medium supplemented with 2% fetal calf serum. Construction of dose response curves for the effects of the two enantiomers on rhodamine 123 accumulation by TM4 cells after 5 hr of drug treatment gave an EC50 of 7.5 micrograms/ml for the (-)gossypol isomer compared with 18 micrograms/ml for the (+)gossypol isomer. Similarly, TM4 cell proliferation was also more disturbed by (-)gossypol in medium supplemented with other concentrations of fetal calf serum. The results suggest that the lower effect of (+)gossypol on TM4 cells may be attributed to its higher affinity to serum components, which may impede its entrance into TM4 cells.

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PubMedDate not supplied

The contraceptive effects of etoprine on male mice and rats.

We had previously found that 2,4-diaminopyrimidines affected spermatogenesis, possibly through the inhibition of testicular dihydrofolate reductase (DHFR). The current study examined the effects of etoprine, a highly lipophilic 2,4-diaminopyrimidine that is also a potent DHFR inhibitor, on the fertility of male mice at various dosages (0.1-50 mg/kg/day) for 55 days and male rats at 5 mg/kg/day for 65 days. Two other substituted diaminopyrimidines were tested at dosages of 50 mg/kg/day for 55 days. Results of breeding trials along with assessment of various parameters indicative of male fertility were noted. We found that of the compounds tested, etoprine is a potent antifertility agent that causes complete infertility at doses of > or = 5 mg/kg/day in mice with a threshold of effectiveness occurring between 1 and 5 mg/kg/day. The antifertility action of etoprine may be related to its capacity to inhibit testicular DHFR and its high degree of lipophilicity.

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