Posted by cybercafe on June 18, 2003, at 12:57:45
In reply to Re: receptor affinity » kotsunega, posted by Larry Hoover on June 18, 2003, at 9:39:43
this is a good post... dr. bob should put it in the FAQ
> > > > > > > Thanks, but I'm still confused a little. What exactly does high affinity mean? I thought it meant the degree of attraction to a specific receptor, but from your post, it sounds like I've got that wrong. Please explain if you can.
>
> Actually affinity is defined in terms of the likelihood of the ligand (the substance binding to the receptor) releasing itself from the receptor site. In other words, affinity is defined as the inverse of dissociation. I'll explain more fully in a moment.
>
> > > > > >
> > > > > > No, you've got it right.
> > > Ok-I read this a LONG time ago, but from what I remember the "numbers" that you see (with regard to "affinity") have to do indirectly with the number of molecules of a given substance it takes to bind to 50% of the receptors (I think outside the body in a dish-but it is close enough analog of what happens in the body that it is useful info).
>
> No, sorry. That's the IC50, or EC50. That's the concentration of a ligand which has the physiological effect of inhibiting or exciting 50% of the available receptors.
>
> Affinity is sometimes expressed as log IC50, but it should state that somewhere. It's really not correct to use that definition, as it embeds receptor response characteristics in the definition.
>
> >So a high number means that a LOT of the substance is required to bind to 50% of the receptors or something along those lines. Of course-this needs to be clarified a lot, I'm sure, but I think that *generally* that is somewhat true.
>
> You're right. If a high concentration is needed to have a 50% effect, then the substance *probably* does not bind strongly to the receptor. However, this is a functional definition. There might be a high binding affinity, but there may be multiple binding sites, all of which need to be occupied, before the receptor function changes measurably.
>
> >
> > Thanks, Ritch. Your description helps me understand the relationship of higher numbers to lower affinity. - Appreciate that. : )
> >
> > -kotsunega
>
> Now, back to the definition of affinity.
>
> If affinity is expressed in terms of K(subscript)d, then you're talking about a standardized term for affinity. K(subscript)d is the ratio of two opposing effects, k(subscript)d (little k), which is the dissociation rate constant, i.e. the tendency of the ligand to release its bond with the receptor as a function of time, and k(subscript)a, the association rate constant, which is the tendency of the ligand to find the receptor in the first place.
>
> k(subscript)a is largely determined by the molecular weight of the ligand; big molecules do not diffuse through solutions as well as small ones can. In practical terms, it is conceived of as a constant, and is sometimes ignored altogether.
>
> k(subscript)d is determined by the ionic and other binding forces acting between the receptor and the ligand. Molecules are not rigid. They vibrate and twist around, and they are constantly being bumped by other molecules. If there's enough momentum at the right moment, the ligand molecule will leave the receptor. The rate at which that happens is k(subscript)d.
>
> K(subscript)d (capital K), is sometimes, then, simplified as the inverse of k(subscript)d, or 1/k(subscript)d. k(subscript)d has units of molecules/sec, so K(subscript)d has units of sec/molecule.
>
> I hope that wasn't too geeky.
>
> Lar
>
>
poster:cybercafe
thread:234389
URL: http://www.dr-bob.org/babble/20030614/msgs/234811.html