Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Hormone 3 Lecture PPT
PERTUSSIS TOXIN
Protein Kinase
? In prokaryotic cells, cAMP binds to a specific protein
called catabolite regulatory protein (CRP) that binds
directly to DNA and influences gene expression.
? By contrast, in eukaryotic cells, cAMP binds to a protein
kinase called protein kinase A (PKA), a heterotetrameric
molecule consisting of two regulatory subunits (R) that
inhibit the activity of the two catalytic subunits (C) when
bound as a tetrameric complex.
? cAMP binding to the R2 C2 tetramer results in the
following reaction:
?
? The R2 C2 complex has no enzymatic activity, but
the binding of cAMP by R induces dissociation of
the R?C complex, thereby activating the latter.
? The active C subunit catalyzes the transfer of the
phosphate of ATP to a serine or threonine residue in
a variety of proteins.
? Protein phosphorylation is now recognized as being
a major and ubiquitous regulatory mechanism.
? The effects of cAMP in
eukaryotic cells are all
thought to be mediated by
- carbohydrate and fat
protein phosphorylation-
metabolism,
dephosphorylation,
- enzyme induction
principally on serine and
- Gene regulation,
threonine residues.
- synaptic transmission, and
-
cell
growth
and
? The control of any of the
replication,
effects
of
cAMP,
could be conferred by a
including such diverse
specific protein kinase,
processes as
by a specific phosphatase,
? steroidogenesis,
or by specific substrates
? secretion,
for phosphorylation
? ion transport
? The array of specific
substrates define a target tissue,
and are involved in defining the extent of a particular
response within a given cell.
? For example, the effects of cAMP on gene
transcription are mediated by CREB, the cyclic AMP
response element binding protein.
? CREB binds to a cAMP responsive DNA enhancer
element (CRE) in its nonphosphorylated state and is a
weak activator of transcription.
? When phosphorylated by PKA, CREB binds the
coactivator CREB-binding protein CBP/p300 and as a
result is a much more potent transcription activator.
? CBP and the related p300 contain histone
acetyltransferase activities, and hence serve as
chromatin-active transcriptional coregulators.
? Interestingly, CBP/p300 can also acetylate certain
transcription factors thereby stimulating their ability
to bind DNA and modulate transcription.
Phosphodiesterases
? Actions caused by hormones that increase cAMP
concentration can be terminated in a number of ways,
including the hydrolysis of cAMP to 5-AMP by
phosphodiesterases
? Phosphodiesterases are subject to regulation by their
substrates, cAMP and cGMP; by hormones; and by
intracellular messengers such as calcium, probably
acting through calmodulin.
? Inhibitors of phosphodiesterase, most notably
methylated xanthine derivatives such as caffeine,
increase intracellular cAMP and mimic or prolong the
actions of hormones through this signal
cGMP :an Intracellular Signal
? Cyclic GMP is made from GTP by the enzyme
guanylyl cyclase, which exists in soluble and
membrane-bound forms.
? Each of these enzyme forms has unique physiologic
properties
? The atriopeptins, a family of peptides produced in
cardiac atrial tissues, cause natriuresis, diuresis,
vasodilation, and inhibition of aldosterone secretion.
? These peptides (eg, atrial natriuretic factor) bind to
and activate the membrane-bound form of guanylyl
cyclase
? This results in an increase of
cGMP by as much as 50-fold in
some cases, and this is thought to mediate the effects
mentioned above.
? A series of compounds, including nitroprusside,
nitroglycerin, nitric oxide, sodium nitrite, and sodium azide,
all cause smooth muscle relaxation and are potent
vasodilators.
? These agents increase cGMP by activating the soluble form
of guanylyl cyclase, and inhibitors of cGMP
phosphodiesterase (the drug sildenafil [Viagra], for example)
enhance and prolong these responses.
? The increased cGMP activates cGMP-dependent protein
kinase (PKG), which in turn phosphorylates a number of
smooth muscle proteins leading to relaxation of smooth
muscle and vasodilation.
This post was last modified on 30 November 2021