You can, as far as reloading from the "mysql>" prompt, use the "system" command, as in:
system su -c '/etc/rc5.d/S20mysql restart'
A better solution, especially for a heavily used system, is to reexamine your configuration, and make improvements. One thing I'd suggest is making sure you have a second server, and set them up for replication. This will allow you to take one machine "offline" for a while, make your changes, then sync with the second server when you're finished. Using virtual machines (such as Xen), you don't even need to add hardware, if that's an issue.
This has numerous benefits. For one thing, you'll have a backup system, if needed. Second, you'll be able to perform backups more efficiently, without losing data or missing transactions, while retaining good end user speeds. Third, especially in your current situation, if there is a problem when you go to restart, you don't end up completely out of luck, having to scramble to undo your changes. Finally, it offers you a second system to test new ideas and software, without major downtime and related headaches.
If your information is that heavily used and important, it's something I'd seriously look into. More info on mysql replication is here:
and Xen info is here:
Hope it helps!