PK structure and regulation Flashcards
PK structure
homotetrameric with several isoforms.
Focusing on PKM1, PKM2 and PKL.
M1 ,M2 = muscle
L = liver
When are PKM2, PKL activated?
when active site is PARTIALLY CLOSED CONFORMATION.
This is caused when FBP is bound allosterically. thisis feedforward inhibition because FBP is a product of PFK1
feedforward activation
FBP is made by PFK1, which was the committed step. If committed step is done, and there is a regulated step coming up, this is saying “look ive made a lot of this so get ready because a lot is coming through” ????? HUH
PKL and PKR are inhibited by?
high ATP concentration
Why?
In liver and reed blood cell, tells you you have enough ATP so dont need to run PK. Can divert out of glycolysis into other pathways, to make something else important
PKL transcription
transcription is referring to availability control, how many copies you have of said enzyme.
PKL is under diet driven transcription, which means when you consume a lot of sugar/carbs, the production of carbohydrate genes are turned on. This causes an increase in PKL concentrations to process the incoming glucose/carbs
PKM1
constitutively active, meaning its always on.
Which PK isoforms are allosterically inhibited by ATP, acetyl co-A, long-chain fatty acids and alanine?
All but PKM1
Acetyl Co-A
Alternative energy source of TCA (fat), breakdown product of LCFA. Signals there is enough energy is concentrations are high, so dont want more pyruvate
Alanine
amino acid, hidden pyruvate.
Pyr is alpha keto acid of alanine
If you have lots of alanine present, can easily get pyruvate….
So if you have a lot of alanine, you have a lot of pyruvate, so dont want to make more
Glucose alanine cycle
If a muscle undergoes glycolysis, going to produce pyruvate. Can convert to alanine, and send to the liver to get rid of an amino group to create pyruvate…
In lover ala converted to pyruvate….. so alanine can inhibit the production of pyruvate
In liver want to create pyruvate to rid yourself of ammonia
Liver +P/-P control
Need a hormone to initiate the process of +p/-p in the liver. This hormone is going to be glucagon,..
Glucagon released in response to low blood sugar.
Glucagon turns on PKA to phosphorylate PKL, which then becomes inactive.
PP
Protein phosphatase PP2A is involved in insulin cascade in the process of +p/-p in the liver
Removes P from PKL to activate PKL
Why is PK regulated
PK is regulated as glycolysis is no longer ATP neutral… dont want to make ATP unneccessarily… will send other metabolites to do other things in other systems.
