The Utilization of Antimetabolites in the Study of Biochemical Processes in Living Organisms

Shive, William

doi:10.1111/j.1749-6632.1950.tb54026.x

Cited by 118 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(1) In the usual 'inhibition analysis' with bacterial cultures (Shive, 1950;Woolley, 1953) half maximal growth is taken as the point at which the ratios of inhibitor to metabolite are determined. This was not feasible in the present type of experiments, as half maximal effects cannot be ascertained with any degree of accuracy when determining the percentage distribution of mitotic phases.…”

Section: Discussionmentioning

confidence: 99%

The function of the Leuconostoc citrovorum factor in cell division and the inactivation of aminopterin

Jacobson¹

1954

The Journal of Physiology

View full text Add to dashboard Cite

As previously recorded (Jacobson, 1954), folic acid antagonists such as aminopterin and A-methopterin arrest mitosis in metaphase; it was also found that certain types of cells are able to overcome this inhibition on more prolonged exposure to the agents. The present study was undertaken with two main objects, (a) to find whether the inhibition of mitosis by the folic acid antagonists is of an unspecific nature or whether it is due to interference with the normal function of a particular substance within the cell; and (b) to discover why certain tissues gradually become 'resistant' to the antagonists.The results showed that the agents probably interfere with the intracellular activity, not of folic acid itself, but of one of its derivatives, viz. the Leuconostoc citrovorum factor (LCF) a 5-formyl, 5: 6: 7: 8-tetrahydro derivative of folic acid. That some tissues gradually become resistant to folic acid antagonists might have been due to either of two alternatives: (1) the cells might use another metabolic pathway, by-passing the block caused by the antagonist and rendering the action of LCF no longer essential for cell division; or (2) the cells might inactivate the inhibitor. As described below, the latter alternative was found to be correct. Structural formulae of the pteridine compounds used in this work are shown in Fig.

show abstract

Section: Discussionmentioning

confidence: 99%

The function of the Leuconostoc citrovorum factor in cell division and the inactivation of aminopterin

Jacobson¹

1954

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…It now seems fairly certain that p-aminobenzoic acid (p-AB) and the folic acid group of factors, in the form of a coenzyme, are concerned in the biological synthesis of purines. It has been suggested (Shive et al 1947) that the coenzyme is responsible for the condensation of a 'one-carbon unit ' with 4-amino-5-imidazolecarbo~mide, or more probably a derivative of it (Shive, 1950;Woods, 1952), to produce the purine nucleus. Since p-AB and pteroylglutamic acid were present in the medium throughout the present work, the purine requirement found may have been due to an inability to complete the synthesis of this coeazyme.…”

Section: Discussionmentioning

confidence: 99%

Growth Factors for Corynebacterium diphtheriae Strain Dundee

Dalby

Holdsworth

1956

Journal of General Microbiology

View full text Add to dashboard Cite

SUMIMARY:Investigations were kontinued on the nature of the growth factor requirements of Corynebacterium diphtheriae gravis, strain Dundee. Hypoxanthine, or adenine + guanine, or adenine + xanthine, were found capable of replacing concentrates of the growth factor from liver and yeast.Nucleoside and nucleotide fractions, prepared from electrophoretically-purified ribonucleic acid, were unable to replace the free purine bases. A purine extract was obtained from an active fish-liver concentrate by copper precipitation. In this extract, a large amount of hypoxanthine and a smaller amount of xanthine were found by chromatography to be the major purine constituents; traces of adenine and guanine were also detected. Chromatographic fractionation and spectrophotometric examination of the fractions confirmed the presence of hypoxanthine and xanthine, whose concentrations were estimated.The purine extract supported less growth than the original fish-liver concentrates.Growth on the purine extract could be reproduced by a mixture of hypoxanthine and xanthine at an equivalent concentration

show abstract

“…There was no improvement of growth by addition of p-hydrozybenzoic acid, alone or together with p-aminobenzoic acid. The inhibition index (Shive, 1950) is a useful concept in considering competitive inhibitions by analogues of metabolites. Table 3).…”

Section: Szll~1tlonamide-resistant Staphylococci 261mentioning

confidence: 99%

Biochemical Properties of Staphylococci Sensitive and Resistant to Sulphonamides

White

Woods

1965

Journal of General Microbiology

View full text Add to dashboard Cite

SUMMARYFour staphylococcal substrains resistant to sulphonamides were developed from sensitive parent strains by subcultivation in increasing concentrations of sulphathiazole. As compared with the parent strains, the growth of the resistant strains was 20-200-fold less sensitive to sulphathiazole in a semi-defined medium based on acid hydrolyzed casein than were the parent strains. Inhibition of growth by sulphathiazole was overcome competitively by p-aminobenzoic acid. The inhibition indices of the sulphathiazole-sensitive strains were about 10, and 10@-1000 for the resistant substrains; the change in index was about proportional to the degree of resistance. The sulphathiazole-resistant strains were cross-resistant to other sulphonamides but were not resistant to p-nitrobenzoic acid. Not one of the sensitive or resistant strains was inhibited by aminopterin.No change in the inhibitory effect of sulphathiazole occurred during growth of cultures in its presence, though the drug was partly converted to a second substance (of unknown structure). Resistant and sensitive pairs of strains formed similar amounts of unknown compound, so that it is unlikely that its formation has to do with resistance. Concentrated suspensions of organisms of all strains took up similar amounts of [~~S]-sulphathiazole when incubated in the growth medium. The attachment of the drug to the organisms was weak, but the uptake was not altered by the presence of p-aminobenzoic acid. The rates of aerobic growth and the nutritional requirements for anaerobic growth of sensitive and resistant strains were generally similar. The nutritional requirements for vitamins and amino acids varied among the sensitive strains, but there were only slight differences between resistant and sensitive pairs of strains.

show abstract

The Utilization of Antimetabolites in the Study of Biochemical Processes in Living Organisms

Cited by 118 publications

References 32 publications

The function of the Leuconostoc citrovorum factor in cell division and the inactivation of aminopterin

The function of the Leuconostoc citrovorum factor in cell division and the inactivation of aminopterin

Growth Factors for Corynebacterium diphtheriae Strain Dundee

Biochemical Properties of Staphylococci Sensitive and Resistant to Sulphonamides

Contact Info

Product

Resources

About