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I will give you an example of vague. This example is located in most
classic textbooks on enzyme kinetics.
There is a substrate S, an enzyme E, an inhibitor I, and a product P.
Consider the three classic types of inhibition: competitive,
non-competitive, and uncompetitive.
Competitive:
E + S --r> E:S --> E + P
E + I --r> E:I
Uncompetitive:
E + S --r> E:S --> E + P
E:S + I --r> E:S:I
Non-competitive:
E + S --r> E:S --> E + P
E + I --r> E:I
E:S + I --r> E:S:I
If you want to use the steady state approximation on these reactions,
the total balance is S --> P with some rate law (Michaelis Menten like).
In your definition of modifier, for the total balance on these reactions
(which is S --> P), the inhibitor and enzyme are both modifiers.
However, the rate laws of all three of these types of inhibition are
different. They all depend on the numbers of molecules of inhibitor and
enzyme differently. To correctly calculate the rates of these reactions,
you then need to know how the modifier affects the rate. The information
for the reaction then needs data for not only the reactants and
products, but also for the 'modifiers'.
This is the simplest of examples. What happens when something more
realistic comes along?
Also, the rate law I gave as a power law is dependent on only the
reactants of the reaction and rightly does not distinguish between
reactants whose stoichiometry is zero or non-zero. Species whose
stoichiometries may be zero for the total balance of the reaction may
still be a variable within the rate law. And that is why the term
'modifier' is vague: it doesn't say how the numbers of molecules of the
species affects the rate of the reaction.
-Howard Salis
Pedro Mendes wrote:
>On Monday 25 April 2005 10:14 pm, Howard Salis wrote:
>
>
>>I think the idea of 'modifiers' is too vague to be useful.
>>
>>
>
>I think the discussions in this list are starting to convince me that anyone
>who wants to be doing any modeling of biochemical systems should first have
>to pass an "Enzyme Kinetics" course. The concept of modifier is not vague
>at all, it is quite well defined. It seems to me that there are a number of
>people out there that want to define this concept according to whatever
>their software thinks a modifier is.
>
>Power-law models do not distinguish between substrates, products or
>modifiers. For power laws everything is an effector (hey, there's another
>word that I expect will have a long discussion too).
>
>As someone else already stated in this thread, a modifier is not changed by
>the reaction therefore the only number that could be attributed to its
>stoichiometry is zero.
>
>Also, reactions do not need any modifier (eg activator) to proceed. If you
>put NADH in contact with oxygen, it is only a matter of time that you end
>up with NADP+ and water - no enzymes required.
>
>Anyway, I am one of the defenders that software should be sufficiently
>user-friendly to allow non-speciallists to carry out simulation. But this
>has always meant to me that they do not need to be speciallists in
>mathematics, numerical analysis, or software engineering. They DO need to
>know biochemistry if they want to model biochemical systems - I'm sorry for
>this lengthy rant, but I am strongly opposed that we should bastardize
>terms that are objective and quite specific (and old) just because some
>software happens to use them in some wrong way.
>
>
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