Regulation of glycolysis and gluconeogenesis

"In the world you will have tribulation. But take heart; I have overcome the world." John 16:33

Where are common points of regulation?

REactions far from equilibruim

What is the mass action ratoio?

Q

Q = ([C][D])/([A][B])

- If Q is within 1-2 orders of magnitude, reaction is near equilibrium

A+B eq symbol C+D

How are reactions far from equilibruim regulated under cellular conditions?

• limited by number of molecules present

• effectors like allosteric regulators

What would happen if reactions with large equilibrium constants were allowed to reach equilibrium?

Some metabolites would be at M concetrations
- would affect homeostasis

How do we control equillibrium reactions?

The enzymes must be sensitive to regulation

• if left unregulated results in high metabolic changes

• when metabolic changes occur, regulating enzymes can adjust

What regulates glycolysis and gluconeogenesis

1. Hexokinase

2. F26BP

Describe hexokinase

• Regulates glycolysis and gluconeogensis

• There are four isozymes

• We only care about 2

What are the 2 hexokinase we care about? What do they do?

1. Hexokinase I a. Muscle

2. Hexokinase IV a. glucokinase b. in the liver

What hexokinase has a higher affinity based on Km?

Hexokinase I
- bc liver can make it's own glucose

What is the first molecule that regulates glycolysis and gluconeogenesis?

Glucokinase has a much higher Km than hexokinase I

What happens when [glucose] is low?

Hexokinase I uptake will predominate to ensure muslce is getting sufficient glucose

Why doesn't the liver get prioritized when [glucose] is low?

Because it can do gluconeogensis to when needed

What happens in the the liver?

Glucokinase is bound by a regulatory protein and sequestered into nucleus out of cytosol

What is the concnetatriaon of glucose in the blood?

5mm, compared to glucokinase at 10mm

What happens when blood [glucose] goes up?

Glucokinase will uptake glucose to liver

- glucokinase released from nucleus to do this

What does the required protein for moving glucokinase out of the cytosol get regulated by?

Allosterically regulated by F6P
- inactivates glucokinase so it doesn't compete with other organse for glucose

What does F26BP regulate?

1. PFK-1

2. FBPase-1

What is F26BP made of?

Made from F6P, which is a substrate of PFK1 product for FBPase-1

the concentratino of F26BP is determined by?

1. Rate of formation and breakdwon
which is hydrolyzed by FBPase-2

What does F26BP activate?

PFK 1, so glycolysis turns off
or
FBPase, so gluconeogeneiss turns off

ensures onepathway is off when the other is on