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Initial response
Lets begin by examining a typical c-AMP-dependent hormone
response system. First we must realize that cAMP action is inside the cell
and the hormone is outside. A connection, therefore, must be made across
the membrane. The connecting point is a receptor for the hormone in close
proximity to a membrane bound enzyme, adenylcyclase (click 1).
Adenylcyclase
Hormone
receptor
GTP
cAMP
ATP
The first reaction is the exchange of GDP with GTP on G protein (click
1). This allows an active G protein to travel to adenylcyclase and stimulate
the enzyme to make cAMP from ATP (click 1). Click 1 to go on.
C C
+ 4 cAMP
C
C
cAMP
R cAMP
R
cAMP
cAMP
You should note at this stage that by raising cAMP levels through an enzyme, the
hormone has dramatically amplified its ability to elicit a response. This is the
advantage of a catalytic (one begets many) as opposed to a stoichiometric (one
begets one) response. Click 1 to go on.
Inactive
Phosphorylase
Kinase
Calmodulin
cAPK
2ATP
2ADP
Active
phosphorylase
Kinase
Catalytic site
Is any protein a target for the catalytic subunit of cAPK? No, only
kinase enzymes will be acted upon. These target enzymes, therefore, must
have some unique features. Phosphorylase kinase, for example, is composed
of 4 different subunits (click 1). The delta subunit is calmodulin, a calcium
binding protein, that regulates the activity (click 1). The gamma subunit has the
catalytic site (click 1). The enzyme is not active. To activate phosphorylase
kinase, the catalytic subunit transfers 2 PO4s from 2 ATPs to the alpha and beta
subunits (click 1). Phosphorylation at these sites renders phosphorylase kinase
active. Conversely, removing phosphate inactivates the kinase. Be alert,
therefore, to phosphatases that may exert control over the function of
phosphorylase kinases. Click 1 to go on.
Crunch Time
Now comes crunch time. What is the function of the target kinases.
The answer is they phosphorylate enzymes that control a critical steps in a
pathway. For example, phosphorylase or glycogen synthase are targets of a
protein kinase. For phosphorylase, the kinase enzyme is phosphorylase kinase.
The sequence of events is highlighted in the figure below (click 1).
Adenylcyclase
cAMP dependent
protein kinase
C C
Phosphorylase
kinase
Phosphorylase
So now you can see how a hormone external to a cell can have a profound
effect on glycogen degradation, glycogen synthesis, and other processes
whose enzymes have activities controlled by the presence or absence of
phosphate groups. Click 1 to test what you learned.