Keyboard shortcuts set in System Preferences broken

I have set up a keyboard shortcut in System Preferences to trigger sending mail in the Mail application.
The shortcut works for a short while after the Mail app is launched, but eventually "breaks" so that when I press the key combo (option-command-s) nothing happens.
I have to quit Mail and relaunch it in order to regain the use of this macro.
This seems like a bug to me!
Can anyone help?
TIA

Hi:
I almost fell on the floor!  The chance of two people in these forums living in a town of 2738 is almost off the scale!  I do live in Johnson Creek - if you are so inclined, you will be able to vote for me (or against me) next year .
Reset the PRAM this way:
http://docs.info.apple.com/article.html?path=Mac/10.7/en/mh26871.html
Reset the SMC this way:  (it is called a SMU on a G5)
http://support.apple.com/kb/HT1767
The preference file is located in Macintosh HD>library>preferences.  (sorry, I edited this, my last post was wrong) 
OS X rebuilds preference files as needed after a restart.  A corrupted preference file may (rare, but it happens) cause odd behavior.
While we are at it, trash another preference file (com.apple.systempreferences.plist) and restart.
Lest see if any of that helps before we look at the Time Machine issue.
Barry
P.S.  Are you really running OS X 10.5.6?  The reason I ask is that I have not run that level of software for a long time.
I need to read profiles more carefully...sorry again
Message was edited by: Barry Hemphill

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