Enzyme Regulation

Front 1

Why regulate?

Back 1

1. grow and differentiate in an orderly manner

2. respond to environmental changes

3. coordinate metabolic processes

Front 2

How to regulate an enzyme?

Back 2

1. control the amount of enzyme present (regulate the rate of transcription, translation, mRNA degradation, or protein degradation)

2. control the activity of the enzyme (altering the conformation or structure by allostery or covalent modification)

3. control the location of the enzyme

Front 3

beta-galactosidase is an example of...

Back 3

an enzyme regulated by transcription regulation

Front 4

acetylcholinesterase is an example of...

Back 4

an enzyme regulated by localization

Front 5

classes of enzyme regulation (by altering the activity of the enzyme)

Back 5

1. feedback inhibition

2. covalent modification

3. binding of a ligand

Front 6

feedback inhibition

Back 6

product of a pathway acts to slow down an initial step (often allostery)

Front 7

example of feedback inhibition

Back 7

ATCase (2 catalytic trimers, 3 regulatory dimers), which catalyzes first step in pyrimidine biosynthesis, is inhibited by downstream product CTP. CTP causes a shift and lock into the T state (does not allow shift in quaternary stucture required for activity).

Front 8

covalent modification requirements

Back 8

1. modification affects active site chemistry

2. modification must be reversible

3. requires enzymes that add and remove the modification

Front 9

example of covalent modification

Back 9

phosphorylation by kinases and dephosphorylations by phosphatases, each of which are subject to their own controls.

Front 10

advantages of covalent modification systems

Back 10

1. able to respond to different allosteric stimuli

2. exhibit great flexibility in control pathways

3. provide potential for enormous signal amplification in response to changes in [effector]

Front 11

example of ligand binding

Back 11

hormone binding to receptors activate heterotrimeric g-proteins that induce cAMP signaling (which then act as second messengers in the cell)

Ca2+ (directly binding a protein; indirectly by binding calmodulin)

Front 12

cAMP control

Back 12

control of adenylate cyclase (ATP->cAMP) (often with g-proteins) and control of phosphodiesterase (cAMP->AMP)

Front 13

G proteins

Back 13

heterotrimeric: consists of α, β, and γ subunits. upon activation of receptor, GTP replaces GDP in α subunit, which dissociates from αβ (change in quaternary structure!) and activates adenylate cyclase (among many others). α has intrinsic GTPase abilities, so natural inactivates.

small g proteins: analogous to α subunit, are similarly activated and inactivated by various proteins and signals

Front 14

Ca2+ control

Back 14

1. direct binding to enzyme

2. binding to calmodulin (switch protein)

Front 15

control of phosphorylase kinase

Back 15

phosphorylase kinase=[αβγδ]₄

αβ=regulatory (subject to phosphorylation by cAMP-PK)

γ=catalytic subunit

δ=calmodulin

in the presence of Ca2+ and calmodulin activity increases! even greater in the presence of cAMP-PK.