Acute And Chronic Enzyme Regulation

Question 0

Allosteric enzyme regulation

Answer 0

Acute
Activators and inhibitors
Weak as non covalent
-> conformational change and therefore affinity change in the enzymes active site

Question 1

Acute enzyme regulation

Answer 1

Fast kinetics-> happens fast
No change in the amount of enzyme as there is no transcription/translation change
Change in activity of existing enzyme

Question 2

Covalent modification for enzyme regulation

Answer 2

Acute
Activators/inhibitors
Covalent attachment of a chemical group -> conformational change of active site
Act by phosphorylation/dephosphorlyation -> kinases and phosphatases-> phosphates added to hydroxyl containing amino acids
Reversible
Phosphate are bulky and charged so change-> electrostatic interactions, conformation, sub cellular distribution
Eg epinephrine increases cAMP via increased adenylate cyclase which-> activates PKA which activated phosphorylase kinase via phosphorylation-> activates GP via phosphorylation-> breaks down glycogen
GP can also be allosterically regulated by AMP-> binding causes relaxation and activation of active site

Question 3

Protein-protein interactions enzyme regulation

Answer 3

Acute 
Ca/calmodulin family
Monmeric or small G protiens
5 families-> Ras,Rho,Rab,Ram,Arf 
Involved in GDP/GTP 
Ras mutations found in 25% of human cancers-> abrogation of normal GTPase activity -> Ras remains in active state -> unregulated activation

Question 4

Proteolytic cleavage enzyme regulation

Answer 4

Acute
Changes in amino acid sequence of protein
Synthesised and secreted in inactive form-> zymogen
Proteolytic cleavage then activates the enzyme
Occurs at site where the enzyme is required to prevent harmful effects of enzyme in other areas
Eg coagulation cascade

Question 5

Chronic enzyme regulation

Answer 5

Change in the transcriptional regulation-> change in amount of enzyme

Question 6

Lactose example of chronic enzyme regulation

Answer 6

Breaks down lactose
Baby-> high lactose activity
Grow up-> decreasing/down regulated lactose activity
75% of adults show some degree of lactose intolerance
Lactose persistence-> C/T variant in regulatory region of lactose gene
-> C associated with down regulation

Question 7

Alcohol metabolism chronic enzyme regulation example

Answer 7

Alcohol dehydrogenase
Originally required for breakdown of naturally occurring alcohols
Amounts vary between people
Regulation
-> transcriptional regulation of gene expression
-> allelic differences in DNA -> ADH1 with differing levels of activity