Enzyme Regulation Flashcards
What 4 things are metabolic enzymes are regulated by?
Compartmentalization- different locations
Enzyme Concentration- on/off switch
Enzyme Activity- volume control
Hormone Signals and Second Messengers- master regulators
Substrate level control acts on a _____ ______
Single reaction
Feedback control targets a _____ ____ __ ____ _______
different step in the pathway
Activators ______ more products
promote
Inhibitors _____ more products
prevent
Isozymes _____ ____ _____ subunits
Mix and Match
What do isozymes do?
They catalyze the same reaction but with different efficiencies
Tissue Specificity: Compartmentalized isozymes
Development: Temporal expression of isozymes
What do reversible covalent modifications do?
They add 1 or more functional group s to inactivate/activate the enzyme
For reversible covalent modifications, post-translational modifications create _________ amino acid
nonproteinogenic- amino acids that are not normally encoded or found in the genetic code
What are the 8 common covalent modifications of protein activity and their donor molecule?
PAM FAGS U
Phosphorylation- ATP
Acetylation- Acetyl CoA
Myrisoylation- Myrisoyl CoA
ADP ribosylation- NAD+
Farnesylation- Farnesyl Pyrophosphate
gamma-Carboxylation- Bicarbonate ion
Sulfation- 3’-Phosphoadenosine- 5’-Phosphosulfate
Ubiquination- Ubiquitin
What are the examples of modified proteins for each of the 8 common covalent modifications?
Phosphorylation- Glycogen phosphorylase
Acetylation- Histones
Myrisoylation- Src
ADP ribosylation- RNA polymerase
Farnesylation- Ras
gamma-Carboxylation- Thrombin
Sulfation- Fibrinogen
Ubiquination- Cyclin
What are the protein functions for each of the 8 common covalent modifications?
Phosphorylation- Glucose homeostasis, energy transduction
Acetylation- DNA packing, transcription
Myrisoylation- Signal Transduction
ADP ribosylation- Transcription
Farnesylation- Signal transduction
gamma-Carboxylation- Blood clotting
Sulfation- Blood clot formation
Ubiquination-Control of cell cycle
What are the 5 categories of molecules each reversible covalent modifications can be found in?
What do carbohydrates provide to the cell?
Lipids- Myristic Acid and Farnesyl
Nucleic Acids- ADP ribose
Proteins- Ubiquitin
Carbohydrates- The greatest source of diversity to the proteome
Small molecules- gamma carboxylation, Sulfation, Acetylation, Methylation
What 4 things does phosphorylation affect?
- Thermodynamics- ATP hydrolysis can drive unfavorable reactions
- Kinetics- Physiological processes dictate reaction time
- Cell processes- ATP amounts dictated by metabolism (energy charge); Signal transduction amplification (catalytic turnover)
- Shape and Charge Complementary- each phosphate adds (-2) charge and possible (3+) H-bonds
Kinases verses phosphatases
Kinases add phosphates Phosphatases remove phosphates *Note that the name of the phosphate indicates which amino acid the phosphate will be added to
Where does allosteric binding NOT occur?
At the active site!
What are the 2 types of Allostery?
Heteroallostery: Effector binds at the allosteric site. The regulation of allosteric enzymes by a molecule other than the substrate. Homoallostery: Substrate induced regulation of allosteric enzymes. These enzymes are invariably multisubunit proteins, with multiple active sites.
An inhibitor will ___ the rate of product formation An activator will ___ the rate of product formation
Inhibit- Decrease Activator- Increase
ATCase is inhibited by what?
Aspartate Carbamoyltransferase (ATCase)
CTP
Binding of CTP prefers the _______
T/inactive state
Binding of ATP prefers the _______
R/active state
Protein synthesis regulation= on/off switch. What are the two levels of control that are possible?
Transcription regulation at the promoters
Translation regulation at the UTRs
What controls Transcription?
Histones
Histone Acetylation ______ Transcription
Promotes
Histone Phosphorylation ______ Transcription
Prevents
Histone Methylarion either _____ or ____ Transcription
Promotes or Prevents
What 2 things control Translation?
miRNAs and UTRs *remember that mRNA levels do not correlate to protein levels
How do we carry out irreversible covalent modification?
Proteolytic activation
In what 4 important molecules do we see proteolytic activation alter enzymes from zymogens to their active state?
Proteases:
- Digestive enzymes
- Collagenase (development)
- Caspases (apoptosis)
Collagen
Blood clotting factors
Insulin/Hormones
For the proteolytic activation of chymotrypsin, what converts chymotrypsinogen to chymotrypsin in the primary structure?
Trypsin- cuts chymotrypsinogen in 4 spots to make 3 chains
Draw out the proteolytic cascade
Find this picture on the last slide of this lecture.
