What are the major types of short-term metabolic regulation?

1) Substrate availability 

2) Confirmational change

     a) allosteric regulation

     b) covalent modification 

What is allosteric regulation and what is the mechanism that it uses for regulation?

• type of short-term regulation
• effector binds non-covalently to a site on the enzyme that is NOT the active site
• can cause a change in the affinity of the enzyme for the substrate OR can cause a change in the rate of the reaction OR both
• mechanism: causes a confirmational change in the substrate binding site 

What is covalent modification and what is the mechanism it uses for regulaiton? 

• type of short term regulation
• phosphorylation (kinases)  or dephosphorylation (phosphatases) of proteins
• Effect occurs in seconds to minutes 
• Mechanism:  the phosphate has a negative charge and it changes the shape/confirmation of enzyme

Slide 7 box questions

• What happens if G à H is blocked?
• What physiological changes will alter hormone secretion?
• By what mechanisms might this change occur? 

• If G-H is blocked, H will not be produced and G will build up 
• Hormone secretion will be altered by stress, starvation, etc. 
• This change may occur if there is a confirmational change in the enzyme or the binding site changes shape.  

• types of metabolic regulation
• permanent: enzymes are generally segregated into specific compartments or organelles
• variable: The function of certain proteins like GLUT4 is regulated by a change in its location from intracellular vesicles to the PM.  Transport of glucose into the cell can only occur when GLUT4 is in the plasma membrane

• Regulation occurs by increasing or decreasing the amount of enzyme present in the cell
• Affects the rate of transcription OR translation to get new protein synthesis 
• Effect is long-term: takes houes or days

• A rate-limiting step in a pathway
• The committed step in a pathway
• An irreversible reaction - one that consumes energy (ATP)
• At a branch point in a pathway

• 12 transmembrane domains
• no ATP is required for most sugar transport
• regulated by: location, concentration gradient, amount of transport protein
• key control steps: rate of solute-carrier interaction (kM for glucose), rate of confirmational change for loaded and unloaded carrier 

(ATP-Binding Cassette)

Many types (B12, sterols,  Cl- , bile)

ATP is hydrolyzed to provide energy for the transport