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Enzymes
General Properties
Life forms, organisms, are complex chemical systems capable of undergoing
metabolism and maintaining homeostasis. Being able to grow and reproduce
and being able to respond to external stimuli.
In order to understand how living systems work, one must understand at the
molecular level the fundamental principles governing the structure, organisation
and function of living matter. The study of these principles is the area of
biochemistry.
At this time it was still believed that living organisms were fundamentally different
from non-living matter. That living organisms contained some sort of mysterious
life force. And that the behaviour of organic matter would not be governed by the
same principles as inorganic matter, established by the study of chemistry and
physics. The central idea of this belief called vitalism, was that organic
substances could only be made in living things.
In humans, animals and plants. Friedrich Wohler discovered that urea, which
was a known substance, excreted by humans and animals, could be synthesised
in the laboratory from inorganic compounds. This was a shocking discovery at
the time, since it violated the clear separation between the living world, and the
non-living inorganic world. The final nail in the coffin of the idea of a mysterious
life force, was a discovery by Eduard Buchner and his brother, Hans Buchner at
the end of the 19th century, that extracts made from broken up dead yeast cells,
could carry out the complete process of fermentation of sugar into ethanol. This
discovery opened up the door for the study of biochemical reactions in the test
tube, in vitro, to identify the molecules involved, and to study their function.
These studies initially focussed on the chemical reactions, and reaction
pathways, in cellular metabolism. And over the last 100 years of so, led to the
identification and structural, and functional characterisation of key biological
molecules, such as proteins and nucleic acids. Which in turn allowed detailed
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, investigations, at the molecular level, of all cellular processes. DNA replication,
gene regulation, cell growths in differentiation, the response of cells to external
stimuli, the molecular basis of disease. And so forth.
We now know that chemical reactions in cells are promoted by enzymes, which
are defined as biological catalysts, that accelerate the rate of chemical reactions
without being changed or consumed.
Enzymes participate in every cellular process, and the study of enzymes,
enzymology is therefore a key area in biochemistry.
Enzymes are generally proteins. I say generally, because RNA is another class
of biological macromolecules that can possess enzymatic activity. Perhaps the
most important feature of enzymes, is that they accelerate specific chemical
reactions, by acting upon a specific reactant.
The reactant acted upon by an enzyme is called the enzyme substrate.
How can we explain that enzymes act upon a single specific substrate? The first
model to explain the specificity of enzymes, for specific substrates, was
postulated by the famous German chemist and biochemist Emil Fischer. Fischer
postulated that enzymes interact with their substrates, similar to how a lock
interacts with a key.
With a lock being the enzyme and the key being the substrate.
Only a substrate of the correct size and shape will fit the active side of the
enzyme, at which catalysis, the acceleration of the chemical reaction, occurs.
However the rigid lock and key model cannot explain all experimental
observations with enzymes. For this reason, the so-called induced fit model was
proposed by the American biochemist Dan Koshland in 1958.
This model poses that active site
and substrate are initially not a
perfect match and that interaction
with the substrate induces changes
in the confirmation of the enzyme,
to maximise enzyme substrate
interactions.
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, Today it is clear that most, if not all enzymes, undergo at least some subtle
structural changes when binding to the substrates.
This slide shows an example with quite significant conformational changes in the
enzyme, the binding of the substrate glucose to the enzyme hexokinase. The
hexokinase structure is shown here as a ribbon or cartoon model with helices
coloured red, beta strands coloured yellow, and loops and turns coloured green.
The left structure model shows hexokinase without glucose.
The right, with glucose bound in its active side, shown as a green space filling
model. If you look at the top left of the enzyme structure, you can see that this
portion of the enzyme twists and folds inwards upon binding of the glucose
molecule.
I should point out that induced fit binding of enzymes of substrates is not a one
way interaction. And that the confirmation of the substrate also changes to adapt
to the active side of the enzyme, during the binding process.
Enzymes play a critical role in cellular metabolism, as they channel chemical
reactions into metabolic pathways. This slide shows the metabolic pathway of
the breakdown of glucose into Pyruvate, called Glycolysis. I’m showing the slide
to show you that these metabolic pathways consist of different chemical reaction
steps each catalysed by a different enzyme.
Enzymes are named and classified based on the chemical reaction they
catalyse.
Most enzyme names end with a
suffix ase. So an enzyme catalysing
the breakdown of RNA would be
called RNase. An enzyme
catalysing the breakdown of
protein, protease and enzyme
catalysing hydrolysis of a substrate
hydrolase and so one.
I’m showing here an overview of enzyme families classified by the international
enzyme commission, as an example for some enzyme names and classes. You
do not have to memorise these classifications.
Many enzymes cannot work on their own, but require so-called cofactors in order
to act upon their substrate, and accelerate a chemical reaction.
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