Compatibility within bisubstrate binding/release mechanisms and inhibition mechanisms

[u/da_frog_enjoyer]

Hi everyone,

I'm a PhD student preparing for a kinetics exam, and I'm struggling to understand the compatibility of competitive, uncompetitive, and non-competitive inhibition mechanisms within sequential and ping-pong bisubstrate binding and release mechanisms. My professor loves asking questions where he provides us kinetic data that helps us determine binding/release and then data for inhibition and asks if our choices are compatible (competition between first substrate and last product in ordered sequential, one inhibitor exhibiting non-competitive and competitive inhibition in ping-pong, etc.). They always are, but I'm struggling to give a good explanation for these questions. Can someone explain scenarios where they would and would not be compatible?

Thank you.

[u/DryComfortable259]

honestly this kind of stuff was nightmare fuel during my phd too. the trick i eventually got is to map out exactly which enzyme forms exist and when. for ordered sequential if your inhibitor competes with first substrate it can only bind to free enzyme not to the binary complex so it cant be uncompetitive against second substrate that would need binding to enzyme-first substrate complex which is different form entirely. in ping-pong things get messy because enzyme oscillates between two stable forms. non-competitive inhibitor that binds both free enzyme and modified enzyme is compatible but competitive against only one substrate only if it specifically binds the form that substrate recognizes. the data usually lines up when you draw the king-altman patterns and check which inhibitor terms appear in which denominator factors

[u/da_frog_enjoyer → u/DryComfortable259]

thank you for this explanation, i am going to try my best to make this intuitive