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E T I E N N E W O L F F
Other inhibitors, namely citrate, malonate, cyanide and sodium
azide, affect the development of the heart and the nervous system in
a manner similar to that of iodoacetate. Malonate is considered by
certain authors to be an inhibitor of succinic-dehydrogenase. This
hypothesis is born out by the fact that its effects can be compensated
partly by the addition of succinate to the culture.
In general terms, metabolic inhibitors affect the same regions of the
blastoderm as do deficiencies of the medium, such as inadequate substrates or anoxia.
(b) Antimetabolites (analogues). Analogues can be used to block certain
processes of synthesis by taking the places of molecules which normally
participate in the reaction. This method was applied by Herrmann
and his colleagues to a problem relating to certain amino acids.
Embryos removed between the stage of head process and the stage
of six somites were cultivated for 24 h on a medium containing agar
and extract of egg, according to Spratt's technique (1947). T w o
analogues of phenylalanine caused inhibition of growth (control: 4 m m ;
test: 2-9 mm) and various malformations ofthe neural tube and of the
somites (the neural tube was sinuous, and the somites small and irregular). The addition of phenylalanine to cultures treated with this
analogue partly re-established growth.
The analogues of leucine had a lesser effect on growth. They inhibited
segmentation of somites. The chlorinated analogue caused temporary
blockage encompassing several somites. The chlorine compound being
unstable, however, segmentation soon began again. However, the stable
bromine compound definitely inhibited the separation of somites.
The action of o;-bromoallylglycine could be completely annulled by
the addition of leucine, and partially avoided by the addition of other
amino acids such as valine, methionine, serine, lysine, and phenylalanine.
Thus the analogues of different amino acids cause inhibitions and
malformations which are relatively specific. The metabolic causes of
these differential effects have not yet been elucidated (Herrmann,
Konigsberg and Curry, 1955).
Schultz and Herrmann (1958) have shown, however, that the effect
of co-bromoallylglycine is to diminish, selectively, the synthesis of
proteins at the level of Hensen's node and of the somites, and also to
diminish the incorporation of labelled glycine at the level of Hensen's
node. Is it inhibition of synthesis or is it acceleration of breakdown
which is involved here? Both solutions are possible, but signs of degeneration are clearly visible in the cells of the somites.
These phenomena are comparable to the results reported by Jensen,
Lehmann and Weber (1956) who observed an increased catheptic
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