Download Homeostasis Receptors Hormones

Homeostasis Receptors Hormones
With Particular emphasis on the specific molecular interactions of
phytochemicals, discuss the means by which mammalian chemical signals
are coupled to elicit cellular responses.
Homeostasis is deriverd from the Greek words: homios ( like, same,
resembling ) and stasis (posture, to stand ) is the maintenance of constancy
of human's internal environment ( and all mammals ). A number of organs
within the body must be coordinated to achieve homeostasis via interaction
and feedback control mechanisms. Cells within the body liberate signal
molecules to communicate ( e.g hormones and neurotransmitters) to maintain
the homeostatic balance. Signal molecules start their actions by binding to
proteins called receptors.
The phytochemicals contained within certain classes of plants, especially the
products of secondary metabolism often chemically resemble human
endogenous signalling molecules. These phytochemicals can affect the way
chemical signals within the human body respond, acting as antagonists (
which bind to receptors, blocking a response ) or agonists ( which can trigger
a response ). The specific ligand, the type of receptor that is acted upon, type
of cell and the interacellular signalling mediators involved determines the type
of response produced.
Most receptors are proteins and can be divided in to four superfamilies.
These are: G-protein coupled receptors, steroid receptors, iontropic ion
channel receptors and receptor Tyrosine Kinases ( TK ).
G- protein receptors ( Guanine nucleotide binding proteins, also known as
seven transmembrane receptors, as they span the cell plasma membrane
seven times ) are the most common receptor type , they evoke cellular
responses as part of a fast acting signalling system. Each G protein is made
up of a specific type of alpha sub unit which responds to specific hormones or
neurotransmitters ( first signal ), and beta/gamma units. The hydrophillic
extracellular part of the G protein binds to the signal molecule ( hormones or
phytochemical ), this causes a change in the shape of the receptor, and a
reduced attraction of the alpha subunit for it is bound Guanosine Diphosphate
( GDP ), which gets released and then replaced by Guanosine Triphosphate (
GTP ). The alpha subunit separates and diffuses through the membrane to a
targetted protein.
The alpha and the beta/gamma subunits can then move freely along the
membrane surface and activate the effector the enzyme adenylate cyclase,
this will catalyse the formation of cyclic adenosine monophosphate ( cAMP )
molecules that act as second messengers carrying the signal and activate
their targets which are no longer confined to the cell membrane. cAMPphosphodiesterase converts cAMP continuously in to non cyclic AMP. Protein
kinase A is activated by cAMP binding to it , which catalyses the
phosphorolation of other enzymes or target proteins Phospholoration
activates some of these proteins and inactivates others a bit like a switch.
The final target protein within the cell is functional, with a specific response
e.g glycogen synthesis or breakdown of a triglyceride. Unless G-proteins are
further stimulated by binding of a hormone at the receptor site
phosphodiesterase inactivates cAMP and the cells response is turned off.
Other second messengers include cyclic guanosine monophosphate ( cGMP
), inositol trisphosphate ( IP3 ) which can raise intracellular calcium levels,
diacylglycerol ( DAG ) which activates Protein Kinase C ( PKC ) and calcium
ions ( Ca2+ ). Nitric oxide activates guanylyl cyclase, this enzyme converts
guanosine triphosphate ( GTP ) to cGMP. This causes calcium ions to enter
storage areas of smooth muscle fibres and as a result this causes muscle
relaxation.
Platelet Activating factor ( PAF ) is an ether lipid signalling molecule, with
effects many body systems and is particularly important in the cellular
immune response. PAF stimulates platelet aggregation and the release of
serotonin from the platelets and is important in haemostasis. It is produced
and released from basophils, endothelial cells, eosinophils, macrophages,
neutrophils, lymphocytes, monocytes and mast cells, which also respond to
PAF. It is important in inflamation and immune responses ( Nelson 2005 ).
Development of respiratory and cardiovascular disorders, allergic response,
anphylactic shock and hypertension is connected with platelet actions. PAF's
actions can be antagonised by a number of phytochemicals, which block the
G-protein coupled receptor with which it binds. Examples include Ginkgolides
found in Gingko Biloba and Ligans and neoligans which include Kadsurenone
found in Piper futukadsura. ( Furukawa, 1997 )
Steroid receptors are intracellular proteins found in the cytoplasm or nucleus
of a cell which bind to and regulate the transcription of DNA under the
regulation of the hydrophobic steroid hormones, via their zinc finger domain.
As opposed to the G-protein receptors this is generally a slow signalling
system. Receptors for the different hormones have strong structural and
functional similarities which point to an evolution from a common ancestral
gene ( Fox 2004 ).The binding between flavanoid phytoestrogens and
oestrogen receptors, and both their ability to compete with endogenous
oestrogen for binding of their receptors and also the activation of oestrogenresponsive genes acting as weak agonists has been the focus of much
research. This may have therapeutic implications in the prevention and
treatment of breast cancer ( ref hoffmann book )
The steroid hormone receptors can be divided in to three functionally distinct
subfamilies, these are: Type I, classical steroid hormone receptors including
the glucocorticoid ( GR ), androgen ( AR ), mineralcorticoid ( MR) and
progesterone receptor, Type II consists of thyroid hormone related receptors
which include RAR, RXR , T3R and VDR and Type III is formed by the
eostrogren ( ER)receptor and a few 'orphan receptors'.
Ionotropic ion channel recptors