The relationship of cellular permeability to the degree of inhibition by amethopterin and pyrimethamine in several species of bacteria.

@article{Wood1961TheRO,
  title={The relationship of cellular permeability to the degree of inhibition by amethopterin and pyrimethamine in several species of bacteria.},
  author={Robert C. Wood and Robert Ferone and George H. Hitchings},
  journal={Biochemical pharmacology},
  year={1961},
  volume={6},
  pages={
          113-24
        }
}
View on PubMed
doi.org
36 Citations
Background Citations
5

36 Citations

Studies on dihydrofolate reductase related to the drug sensitivity of microbial and neoplastic cells.

  • C. A. Nichol
  • Biology, Chemistry
    Advances in enzyme regulation
  • 1968

Studies of (3H)folic acid uptake by Lactobacillus casei.

  • B. Cooper
  • Biology
    Biochimica et biophysica acta
  • 1970

Functions of Tetrahydrofolate and the Role of Dihydrofolate Reductase in Cellular Metabolism

Most of the work described in this chapter has been carried out with monoglutamate forms, but it is becoming quite clear that the bulk of intracellular folates are polyglutamate derivatives (e.g., Mackenzie and Baugh 1980).

FOLATE ANTAGONISTS AS ANTIBACTERIAL and ANTIPROTOZOAL AGENTS

  • G. Hitchings
  • Chemistry, Biology
    Annals of the New York Academy of Sciences
  • 1971
The elaboration of the concept of the mechanism of action and its documentation required developments that came gradually over an extended period and are still incomplete, since pure enzymes, sequence determinations and construction of three-dimensional models remain for the future.

Transport of folate compounds into Lactobacillus Casei.

Antimetabolites from microorganisms.

Separation of Folic Acid Reductase from Streptococcus faecium (ATCC 8043)

It is concluded that folic acid is reduced to tetrahydrofolic acid by one enzyme in S. faecium (ATCC 8043) and the reductive activity is located in the soluble fraction of the cell.

Antagonists in Man *

The folate antagonists, in particular amethoptenin (methotrexate), continue to be useful drugs for the treatment of certain neoplastic diseases in man and their effectiveness appears to be a consequence of inhibition of the enzyme dihydrofolate reductase.

Resistance to inhibitors of dihydrofolate reductase in strains of Lactobacillus casei and Proteus vulgaris.

Strains of Lactobacillus casei and Proteus vulgaris resistant to small molecule inhibitors of dihydrofolate reductase were isolated under various nutritional conditions, suggesting that resistance was accompanied by the appearance of a permeability or transport system for thymine.

Folate cofactor biosynthesis by Plasmodium berghei. Comparison of folate and dihydrofolate as substrates.

Dhydrofolate was a good substrate for the synthesis of folinate by uninfected and parasitized erythrocytes, and by free parasites, consistent with the hypothesis that plasmodia synthesize folate cofactors de novo, and do not utilize exogenous folates.

36 References

EFFECT OF FOLIC ACID ANALOGUES ON GROWTH AND CELL DIVISION OF NONEXACTING MICROORGANISMS

It appeared of interest, therefore, to (letermine whether analogues of folic acid were capable also of inhibiting cell division in cultures of microoiganisms, particularly those which do not exhibit a nutritional requirement for folic Acid.

A study of the uptake and degradation of folic acid, citrovorum factor, aminopterin, and pyrimethamine by bacteria.

DIFFERENTIAL REVERSAL OF INHIBITORY EFFECTS OF FOLIC ACID ANALOGUES ON GROWTH, DIVISION, AND DEOXYRIBONUCLEIC ACID SYNTHESIS OF MICROORGANISMS

In the work reported in the present paper, low concentrations of certain folic acid analogues are shown to inhibit division to a greater extent than they inhibit growth.

ANTAGONISM OF THE INHIBITORY ACTION OF AMINOSALICYLIC ACID ON MYCOBACTERIUM TUBERCULOSIS BY METHIONINE, BIOTIN AND CERTAIN FATTY ACIDS, AMINO ACIDS, AND PURINES

The bacteriostatic activity of p-aminosalicylic acid (PAS) for Mycobacterium tuberculosis was discovered by Lehman (1946) in the search for a substance which would inhibit the stimulatory effect of…

UPTAKE OF AMINOPTERIN BY BACILLUS SUBTILIS

The 2-methyl-4-amino-5-hydroxymethylpyrimidine form of the thiamine pyrimidine has been examined for its effect on the entry of aminopterin-2-C04 into B. subtilis.

Some effects of 2-deaminopteroylglutamic acid upon bacterial growth.

Inhibition of the or anism was most marked in the presence of pteroic acid, and became relatively more efficient as the concentrations of inhibitor and growth factor were increased, and 2-deamhopteroylglutamk acid was inhibitory.

PREVENTION OF AMETHOPTERIN INHIBITION BY 2-METHYLADENINE

A group of compounds (certain substituted purines) which was also active in preventing the inhibition of amethopterin, although much less effectively thanThiamine or the thiamine pyrimidine was the most active.

Selection of Bacterial Mutants of Increased Sensitivity to ‘Aminopterin’

This communication concerns the reproducible selection in the absence of the drug of bacterial mutants of increased sensitivity to a folic acid antagonist (‘Aminopterin’).

REVERSAL OF AMINOPTERIN INHIBITION IN BACILLUS SUBTILIS AT THE SITE OF DRUG ENTRY

The present findings give confirmatory evidence for the transport system for the cellular transport of aminopterin as the site of reversal.

Aminopterin inhibition in Aerobacter aerogenes; alanine and valine accumulation during the inhibition and their utilization on recovery.

  • M. Webb
  • Biology
    The Biochemical journal
  • 1958
The inactivation ofthe folic acid antagonist aminopterin (4-amino-4-deoxypteroylglutamic acid) in cultures of Aerobacter aerogenes has been shown to occur by oxidative cleavage with the formation of…