Biology Reference
In-Depth Information
It was not, though, surprising that Winder and O'Hara [ 9 ] reported consider-
able decreases in activity of many iron-containing enzymes. These included vari-
ous cytochromes. These findings were subsequently confirmed by McCready
and Ratledge [ 20 ] also working with M. smegmatis . Non-haem iron in the cells
dropped to ~0.2 nmol/g CDW from ~5 nmol/g CDW and cytochromes a and b
could not be detected. However, cytochrome c was scarcely affected, as were the
flavoproteins, indicating that these iron-containing components were, to some
extent, protected from the severest ravages of iron deficiency. Presumably these
components have very high affinities for iron and thus can acquire iron even when
it was available in the smallest concentrations inside the cell and against competi-
tion from other iron-dependent cytochromes and enzymes.
Iron deficiency therefore produces a major diminution of most components in the
respiratory chain and this, in turn, will inevitably cause a decline in activity of gly-
colytic enzymes as the final oxidation of pyruvate, via the tricarboxylic acid cycle
and its linkage to oxidative phosphorylation that involves many cytochromes, would
be seriously impaired by iron deficiency. Thus, it is not unexpected to find a general
down-regulation of many enzyme activities in the central pathways of metabolism
simply as a consequence of there being diminished energy (ATP) production.
It was apparent from these experiments of the 1960s and 1970s that iron defi-
ciency in mycobacteria was causing the cells to become 'anaemic', somewhat
equivalent to the condition that seen in humans and other animals. Cells became
'lethargic': they had a diminished supply of energy, failed to grow properly and
failed to carry out normal metabolism. They also become noticeably much paler
than cells grown with a surfeit of iron. McCready and Ratledge [ 20 ] and McCready
[ 21 ] found that the content of porphyrins in iron deficient cells was adversely
affected: in M smegmatis , coproporphyrin III was less than 25 μ mol/g CDW after
iron deficient growth compared to over 200 μ mol/g CDW in cells grown iron suf-
ficiently. It is then this absence of porphyrin that accounts for the very pale appear-
ance (the 'anaemic' condition) of the iron-deficient cells. This low content of
porphyrin was later also observed in iron-deficiently grown M. avium [Barclay and
Ratledge, unpublished work in the 1980s] and may then be a general explanation for
most mycobacteria being much paler when grown without adequate amounts of iron.
This phenomenon, which is not seen with other bacteria, must be caused by repres-
sion of the biosynthesis of the porphyrin nucleus due to lack of iron in the cells. This
makes metabolic sense. Why synthesize something that cannot be converted into the
end-product: haem? Therefore stopping the synthesising of the precursor of haem is
a sensible metabolic strategy under iron deficient conditions.
But this then poses a major problem to the cells: if iron then becomes available
to the cells for whatever reason, what are the cells going to do with this iron if it
cannot be immediately converted into haem because there are no precursor mol-
ecules of porphyrin available? Up-regulation of porphyrin biosynthesis cannot be
immediate. The cells must therefore have some means of acquiring the iron and
holding it in a form which can then be mobilized as porphyrins begin to be re-
synthesized. This aspect of iron metabolism then is considered in the next section
of this review.
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