Microorganisms, like the rest of us, live in a changing world, and their needs do not always remain the same. It would be highly inefficient and (frequently wasteful) if all their metabolic reactions were going on with equal intensity all the time, regardless of whether they were needed. Over evolutionary time, regulation systems have developed, so that metabolism is tailored to the prevailing conditions.
Essentially, this regulation involves controlling the activity of enzymes which direct the many biochemical reactions occurring in each cell. This can be done by:
• directly affecting enzyme activity, or
• indirectly, at the genetic level, by controlling the level at which enzymes are synthesised.
Direct control of enzymatic activity occurs by the mechanism of feedback inhibition (see Box 6.5), whereby the final product of a metabolic pathway acts as an inhibitor to the enzyme that catalyses an early step (usually the first) in the pathway. It thus prevents
Biosynthetic pathways exist as a series of enzyme-mediated reactions, leading to a final product required by the cell for structural or metabolic purposes. But what happens if for some reason, the consumption of the final product slows down, or even stops? Feedback inhibition, also known, perhaps more descriptively, as 'end-product inhibition', ensures that excess amounts of the end product are not synthe-sised. The pathways leading to the synthesis of many amino acids are regulated in this way, for example isoleucine, which is synthesised from another amino acid, threonine, via a series of intermediates:
Here, the isoleucine itself acts as an inhibitor of threonine deaminase, the enzyme which starts off the pathway. It does this by binding to an allosteric site on the enzyme, distorting it and preventing its active site from binding to threonine. Note, that by inhibiting the early part of the pathway, we not only prevent further production of isoleucine but also unnecessary breakdown of threonine. When levels of isoleucine starts to run low, less will be available to block the threonine deaminase, and thus the pathway starts to function again.
more of its own formation. When the concentration of the product subsequently falls below a certain level, it is no longer inhibitory, and biosynthesis resumes.
Regulation of metabolic pathways can also be achieved by controlling whether or not an enzyme is synthesised in the first place, and if so, the rate at which it is produced. This is done at the DNA level, by one of two mechanisms, induction and repression, which respectively 'switch on' and 'switch off' the machinery of protein synthesis discussed earlier in this chapter. These are discussed under the heading 'Regulation of gene expression' in Chapter 11
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