1- Classification of hormones:
* Water-soluble hormones
– Hormones catecholamines (adrenaline) -> derived from an amino acid (tyrosine)
– Peptide Hormones (hypothalamic hormones TRH …)
– Protein hormones (insulin)
* Fat soluble hormones
– Steroidal hormones (cortisol, testosterone) -> derivatives of cholesterol
– Thyroid hormones (thyroxine) -> derived from an amino acid (tyrosine)
– The fat-soluble hormones need a vehicle (carrier) to transport to the target cell. It is proteinaceous.
– Hormones related to their carrier are inactive and are not eliminated by the liver or kidney => hormone reservoir (> 90% of the total hormone).
– There are two types of carriers: non specific transporters (low affinity, many binding site) and specific carriers that attach That a single type hormone (high affinity (Kd low), limited number of binding sites )
* Common features
– Hormonal specificity (fixed only one type of hormone)
– A high affinity (structural complementarity)
– Number of sites in the limited cell (103 to 105)
– Organ specificity
– Reversibility of the interaction (non-covalent bonding)
* Note: the anti-hormones are molecules that have an analogy hormone structure; act competitively to occupy the hormone of sites but once fixed does not trigger a response.
4- Membrane Receptors:
A- G protein-coupled Receptors:
* G proteins are glycoproteins able to bind guanine nucleotides (GDP). Have three subunits (α, ß, γ) organized into seven transmembrane domains. The NH 2 portion is the extracellular side. The third intracellular loop and the large cytoplasmic hydrophilic terminal domain involved in receptor-G protein interaction Fixed α subunit the GDP
* The binding of ligand to receptor results in an exchange GDP -> GTP and dissociation of the α subunit -> α-GTP. The α-GTP complex will provide an activating or inhibitory signal to an effector -> second messenger …
* The G protein plays two roles: a role transduction (molecular switch) signal between the receiver and the enzymatic effector and a signal amplifying part
* There are many types of G protein (varying only α subunit)
– Protein Gs: stimulates adenylyl cyclase
– Protein Gi: inhibits adenylyl cyclase (M2 muscarinic receptor => bradycardia)
– Protein Gq: stimulates phospholipase C
|Effector||2 messengered||Action||r ECEIVER (Exp.)|
|Adenylyl cyclase||CAMP||Activation of protein kinase A (PKA)
® Protein phosphorylation
|Phospholipase C (PLC)||IP3||Release of intracellular compartments Ca² + ions (sarcoplasmic reticulum)||1 receiver|
|Phospholipase C||DAG||Activation of protein kinase C (PKC) dependent Ca² +|
* The limitation of action in second messenger is done by:
– Phosphodiesterase (phosphatase) => cAMP degradation (inhibited by theophylline)
– The Ca ++ ATPase pump at the plasma membrane, sarcoplasmic reticulum => decreased cytoplasmic Ca² +. (Also the exchanger Na + / Ca ++ -> heart)
* NB: the calcium pump in the mitochondria is slow and acts as a calcium reservoir and not too full of excitement / stop excitement.
* NB: the calcium ion acts as a second messenger. It can bind to a calciprotéine (calmodulin, troponin C) to activate an enzyme.
– Adrenergic receptors ß => Gs protein -> activates adenylyl cyclase -> cAMP elevation
– Adrenergic receptors α1 => Gq protein to the PLC -> IP3 -> Ca ++ elevation
– Adrenergic receptors α2 => Gi protein -> inhibits adenylyl cyclase -> down cAMP
* Some hormones induce desensitization after binding to their receptors. Receptor phosphorylation site queux C-terminal by a particular kinase (ß-ARK) prevents the binding of adrenaline to its beta receptor.
B- Receptors with enzymatic activity:
– Tyrosine kinase receptor (insulin receptor). Formed by 2 subunit (α, ß) in pairs -> autophosphorylation of tyrosine
– Guanylyl cyclase activity Receiver -> cGMP -> protein kinase G
– Tyrosine phosphorylase.