Aromatic steroid structure

Protection against one particular research toxin (7,12-DMBA) has been noted with acute usage of 9mmol/kg calcium-D-glucarate ( 3 hours prior to and another dose 30 minutes prior to DMBA injections) which reduced tumor occurrence from 100% to 30% [7] and studies with more chronic loading have noted benefit with dietary supplementation of 75mmol/kg (of the diet, /kg bodyweight and 213mg/kg human equivalent). [1] [7] This protective effect extends beyond breast cancer and is able to attenuate skin cancer with either calcium-D-glucarate itself [22] or the main bioactive metabolite [23] (skin cancer is known to be able to be induced by DMBA [24] ) and may also extend to DMBA induced oral cancers. [25]

Thus a local conformational change initiated by the agonist, but not antagonist binding results in a destabilization of the protein structure. This destabilization is not strong enough to denature the protein, but results in a long range effect across the protein affecting its active site several angstrom away from the ligand binding site. This is known as an allosteric mechanism. As a rule, agonists induce structure destabilization, while antagonists merely bind , but do not affect the protein structure (or trigger a conformational change that locks a protein in its inactive position). One way to visualize the action of ligands on receptors is to realize that proteins constantly undergo conformational changes which is best described as an equilibrium between an active and inactive, or even among multiple states, including desensitized states (different types of inactive states). Agonists and antagonists shift this equilibrium towards an active or inactive conformation, respectively.

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Aromatic steroid structure

aromatic steroid structure

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