Posted by Ritch on June 19, 2003, at 11:20:25
In reply to Re: receptor affinity (two definitions..Aarghh!), posted by Larry Hoover on June 18, 2003, at 14:15:20
> >
> > > > > 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.
> >
> > There is a commonly used definition of Kd that is in molar units (concentration), simply the concentration at which 50% of the receptor sites are occupied.
> >
> > See: http://biosci.usc.edu/courses/2001-spring/documents/bisc411-handout24.pdf
>
> Under this definition, affinity increases as Kd *decreases* (negative correlation). And, Kd would have values such as "6.2 x 10(superscript)-8 M", or units in micromolar (10 exp. -6 M), nanomolar (10 exp. -9 M), even picomolar (10 exp. -12 M).
>
> > > 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.
> >
> > This definition is supported by:
> > http://www.nanomedicine.com/NMI/3.5.2.htm
> >
> > It seems my brain filtered out the volume term in my definition of Kd, so it is possible there is some commonality in the definitions, but the latter one involves time (rate), so there are differences, too.
>
> Under this definition, affinity increases as Kd *increases* (positive correlation). High affinity ligands would have lower kd values, so 1/kd would be relatively large. However, Kd under this definition could have values much smaller than, or much greater than, 1.
>
> These two Kd's measure different things, and behave in opposite ways from each other. No friggin' wonder this is confusing.
>
> :-/
>
> Lar
Hi Larry, I had this feeling it had to do with "number of molecules" at bottom, or ultimately how easily one given molecule of the substance will bind to one receptor. Interesting stuff-wished I would have taken more than one chemistry class, though! I got panic attacks in those large college lecture halls-maybe it was the sinister looking sinks with the black chemical-resistant tops? ;)
poster:Ritch
thread:234389
URL: http://www.dr-bob.org/babble/20030619/msgs/235079.html