What
Is a Zymogen?
How they are formed?
When
cells make enzymes, especially proteases, they often make them as zymogen, an
inactive form of the enzyme. This is so they don't go crazy and are only used
when needed. Imagine your reaction if your blender suddenly hopped about on the
counter, out of control, spewing half-chopped fruit everywhere. The counter
would be a mess, and so would the cell.
You
can recognize most zymogens by their name. Enzymes that begin with 'pro-' or
end with '-gen' are often the zymogen form. PepsinoGEN is the zymogen form of
pepsin, the enzyme found in your stomach that helps digest food.
Zymogens, rather than active enzymes, are typically secreted
by the human body, because they can be stored and transported safely without
harms to surrounding tissues, and released when conditions are favorable for
optimal activity. Most of the digestive proteases produced in the pancreas are
expressed as zymogens and retained in such form in zymogen granules. The
contents of these granules are only released into the small intestine during
eating, and the zymogens are only activated once they enter the small
intestine. The latter step is initiated by an intestinal protease,
enterokinase. For example, pepsin is synthesized in the form of pepsinogen, an
inactive zymogen which is secreted by the chief cells. Pepsin becomes active
once pH drops below 5, and works optimally at pH 2-3 in the acidic environment
of the stomach. Activation of pepsinogen starts with the hydrocholoric acid
(HCl), which is secreted by the parietal cells. The acid partially activates
pepsinogen by drastically lowering pH. The partially activated pepsinogen is
then completely activated and turned into pepsinby another pepsinogen through
cleavage of a short peptide. Under rare circumstances, incorrect activation of
these zymogens within the pancreas could result inpancreatitis and lead to
devastating consequences.
Zymogen Activation
Zymogens are activated by snipping
the bonds between two or more amino acids, rather like cutting a balloon string
so that it floats away.
When the bonds are cut, the enzyme changes
its conformation, its 3-D structure, so that the active site is
free or able to become active.
Upon activation, sometimes pieces of
the protein completely leave the enzyme, like taking the wrapper off a candy
bar. Other times, the pieces of protein fold in and become part of the enzyme,
like a catapult being pulled back.
Zymogens
can be activated by proteases that cut the amino acid bonds. They can also be
activated by the environment and become autocatalytic.
Autocatalysis is
self-activation, and happens when something in the environment allows the
zymogen to cut its own chemical bonds.
Pancreas secretes zymogens
Fungi
Fungi also secrete
digestive enzymes into the environment as zymogens. The external environment
has a different pH than inside the fungal cell and this changes the zymogen’s
structure into an active enzyme.
Coenzyme
Another way that enzymes can exist in inactive forms and later be
converted to active forms is by activating only when a cofactor, called a
coenzyme, is bound. In this system, the inactive form (the apoenzyme) becomes
the active form (the holoenzyme) when the coenzyme binds.
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