Download MBBS Hormone 3 Lecture PPT

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