332
MAURICE WELSCH
Oxytetracycline occurring in vivo are believed to be calcium and magnesium complexes (324). Tetracycline inhibition of essential enzymatic
reactions as a consequence of sequestration of necessary ions cannot be
retained as a general explanation of their many observed effects. Thus,
inhibition by Chlortetracycline of leucine incorporation into proteins is
not reversed by magnesium ions (325).
Interference of tetracyclines with essential metabolites is stressed by
the fact that their antibiotic effects may be reversed by as yet unidentified substances present in culture filtrates from resistant microorganisms.
Two metabolites of general importance are especially suspected of being
the main targets responsible for tetracycline activity: flavoproteins and
glutamic acid.
Riboflavin is able to reverse the antibacterial effects of Chlortetracycline, which, possibly on account of structural analogy, competitively
inhibits both the synthesis and the utilization of the vitamin. On the
other hand, Oxytetracycline has the capacity of strongly binding riboflavin (but also other biological compounds featuring similarly fused
rings such as deoxyribonucleic acid and adenylic acid), and the inhibitory effect of Chlortetracycline on D-amino acid oxidase appears as the
result of a competition, for the same binding site of flavin adenine dinucleotide, between the antibiotic and the enzyme protein. Chlortetracycline is also supposed to interfere with the electron transport mechanism by preventing the reoxidation of reduced flavoprotein.
The analogy of the A ring of tetracyclines to glutamic acid, joined to
the fact that integrity of that part of the molecule is necessary for its
biological activity, has led to the suggestion that the antibiotics interfere
with the metabolism of the amino acid. Oxytetracycline inhibits the
incorporation of D-glutamic acid (244a), and also of lysine (122), into
the bacterial cell wall.
III. Conclusions
It is obvious that the production of metabolites endowed with antibiotic activity is a widespread property of microorganisms.
These active substances comprise an infinite variety of widely different chemicals. Although they have been tentatively classified, on the
basis of their structure and biosynthesis, within the classical categories
of fundamental metabolites, of which they offer innumerable variations,
they include many types of new compounds. Their occurrence as families
of related substances, including antibiotically inert ones, and the frequent
production of identical or closely similar compounds by very different
organisms, should be stressed.
These general considerations raise a number of highly controversial
MAURICE WELSCH
Oxytetracycline occurring in vivo are believed to be calcium and magnesium complexes (324). Tetracycline inhibition of essential enzymatic
reactions as a consequence of sequestration of necessary ions cannot be
retained as a general explanation of their many observed effects. Thus,
inhibition by Chlortetracycline of leucine incorporation into proteins is
not reversed by magnesium ions (325).
Interference of tetracyclines with essential metabolites is stressed by
the fact that their antibiotic effects may be reversed by as yet unidentified substances present in culture filtrates from resistant microorganisms.
Two metabolites of general importance are especially suspected of being
the main targets responsible for tetracycline activity: flavoproteins and
glutamic acid.
Riboflavin is able to reverse the antibacterial effects of Chlortetracycline, which, possibly on account of structural analogy, competitively
inhibits both the synthesis and the utilization of the vitamin. On the
other hand, Oxytetracycline has the capacity of strongly binding riboflavin (but also other biological compounds featuring similarly fused
rings such as deoxyribonucleic acid and adenylic acid), and the inhibitory effect of Chlortetracycline on D-amino acid oxidase appears as the
result of a competition, for the same binding site of flavin adenine dinucleotide, between the antibiotic and the enzyme protein. Chlortetracycline is also supposed to interfere with the electron transport mechanism by preventing the reoxidation of reduced flavoprotein.
The analogy of the A ring of tetracyclines to glutamic acid, joined to
the fact that integrity of that part of the molecule is necessary for its
biological activity, has led to the suggestion that the antibiotics interfere
with the metabolism of the amino acid. Oxytetracycline inhibits the
incorporation of D-glutamic acid (244a), and also of lysine (122), into
the bacterial cell wall.
III. Conclusions
It is obvious that the production of metabolites endowed with antibiotic activity is a widespread property of microorganisms.
These active substances comprise an infinite variety of widely different chemicals. Although they have been tentatively classified, on the
basis of their structure and biosynthesis, within the classical categories
of fundamental metabolites, of which they offer innumerable variations,
they include many types of new compounds. Their occurrence as families
of related substances, including antibiotically inert ones, and the frequent
production of identical or closely similar compounds by very different
organisms, should be stressed.
These general considerations raise a number of highly controversial