Lecture 4: Regulation

Question 1

What is the purpose of regulation?

Answer 1

-maintain homeostasis; levels of metabolites must be altered very rapidly.

Question 2

What are the four types of regulation?

Answer 2

1. Substrate accessibility/availability:
   ~Le Chatlier’s
   ~Compartmentalization in organelles or cytosol
2. Allosteric binding to enzymes by activators or inhibitors:
   ~Feedback inhibition.
3. Covalent modification of enzymes:
   ~phosphorylation.
4. Synthesis and degradation of enzymes:
   ~altered transportation/translation.

Question 3

Hexokinase vs PFK-1, and which has a greater affect on metabolic flux:

Answer 3

• Increased hexokinase activity enables glucose activation.
• Increased PFK-1 activity enables catablosim of activated glucose via glycolysis.
• Hexokinase affects flux more than PFK-1.

Question 4

Name two isozymes of hexokinase:

Answer 4

1. HK1: expressed in all tissues.
2. HK4: expressed in Liver.
   ~function: clear blood glucose at higher concentrations for storage as glycogen.
   ~Not inhibited by G6Pase, can still function at higher [glucose].
   ~regulated by sequestration and transcription.

Question 5

How is PFK-1 and FBPase regulated:

Answer 5

• ATP is a negative effector.
• “dont spend glucose in glycolysis if plenty of ATP.
• PFK-1: favor glycolysis if low [ATP] and [AMP].
• FBPase-1: Favor gluconeogenesis if low [AMP]

Question 6

What is the role of fructose 2, 6BPase (via PFK-2 and FBPase):

Answer 6

• Allosteric activator
• F-2,6-BP made by PFK-2.
• Indicator of glucose availability.
• Activates PFK-1 and inhibits FBPase.

Question 7

Regulation of F-2,6-BP levels:

Answer 7

-PFK-2 controlled in liver.
- Glucagon:
~low blood [glucose] signals —> Decrease PFK-2 —> Decrease PFK-1 activity —> decrease glycolysis.