Lecture 9

Question 1

Why is it important for the nitrogen in the pyridinium part of PLP to remain protonated?

Answer 1

If the Nitrogen is protonated, then it is a better electron sink which is important for the mechanisms that use PLP as a co-factor

Question 2

What are some examples of reactions that PLP catalyzes? (3)

Answer 2

1) Decarboxylation
2) Side chain cleavage
3) Transamination

Question 3

Describe the “mechanistic logic” of using PLP (5)

Answer 3

1) PLP is primed by iminium formation with lysine residue in active site
2) Electrophilic iminium of primed PLP reacts with nucleophilic nitrogen atom of substrate to form another iminium ion, essentially trading one iminium ion for another
3) New PLP iminium accepts electron density from broken sigma bond acting as electron sink
4) Electron density from enamine (full electron sink) is released to attack an electrophile
5) The product is released from PLP by hydrolysis or attack from lysine in active site

Question 4

For decarboxylation using PLP, what is the donor orbital? What is the acceptor orbital?

Answer 4

Donor: sigma c-c
Acceptor: pi*c=n
In order for decarboxylation to occur, the donor orbital must be aligned with the conjugated pi-system of PLP and the pyridinium nitrogen must be protonated