Enzyme regulation Flashcards
Benefits to multiple regulation mechanisms for a single pathway
- Failsafe mechanism
- Different signals, different mechanisms - can be regulated by various different things
- Allows different speeds of regulation (transcription, long - phosphorylation, quick)
- Allows degree of regulation?
Allosteric reguylartion
Allos - other
steros - shape
Phosphorylation
Ser, Thr, Tyr - moderately polar
- Bulky charged group added
- Potential hydrogen bonds can be formed
- Negative charge
- Three-dimensional structure - enzyme conformation, substrate binding and catalysis
Consensus sequences - sequences that determine whether a protein will be phosphorylated, allows specificity by making it so that not all proteins get phosphorylated
Types of enzyme regulatory control
- Activity (fine control) - covalent modification, allostery, etc
- Quantity (coarse control) - transcription, translation, degradation, etc
- Global control (long-term coarse) - hormones influencing amounts
- Local control (fine) - citrate, AMP, fatty acids control
Feedback regulation vs sequential feedback regulation
The final end-product inhibits the first reaction, preventing intermediate build-up
Occurs in branched pathways, and follows the same sort of process as typical feedback regulation
Competitive inhibition: effects on Vₘₐₓ and Kₘ
Vₘₐₓ unchanged - only binding is affected, RoR is unaffected
Kₘ increased - E-S binding is affected
Hekoinase: how can it be regulated?
Glucokinase regulatory protein sequesters hexokinase IV (glucokinase) in the nucleus - a type of type VI regulation, using different subcellular compartments to regulate enzyme activity
- mRNA stability
- Degradation
- Allostery
- Compartmentalisation
- Transcription
PP2A: how can it be regulated?
Phosphoprotein phosphatase 2A (PP2A)
* Recognizes several substrate proteins
* Specificity is determined by regulatory subunit
*Creates unique substrate binding site - conferring specificity
Threonine deaminase
In the conversion of Threonine into Isoleucine in E.Coli, isoleucine acts as an allosteric inhibitor of threonine deaminase, the first enzyme in the pathway
Feedback inhibition
Succinate dehydrogenase
Important role in TCA - converts succinate (COO⁻-CH₂-CH₂-COO⁻) into fumarate (COO⁻-CH=CH-COO⁻)
Competitivively inhibited by malonate (COO⁻-CH₂-COO⁻)
DFP
Modifies serine in acetylcholinesterase by forming a covalent bond with the active bond
Fructose 1,6-bisphosphatase
Important in gluconeogenesis - converts fructose 1,6 bisphosphate into fructose-6-phosphate
Inhibited by AMP - high AMP cell needs energy, glucose synthesis is inhibited so ATP can be produced
DAHP synthase
Catalyses Phosphoenolpyruvate and Erythrose-4-phosphate joining
Type of sequential feedback regulation:
* End-product tryptophan does not inhibit DAHP synthase, the first intermediate that branches towards it does (chorismate)
* End-product phenylalanine/tyrosine do not inhibit DAHP synthase, the first intermediate that branches towards them does (prephenate)
Purine biosynthesis - ATase
Amidophosphoribosyl transferase
Produce AMP/GMP
AMP/GMP separately inhibit but when both are present inhibition is much higher - this is advantageous so roughly equal amounts of AMP/GMP are produced
Glycogen phosphorylase
Dimer with 2 interconvertible forms:
* Active - phosphorylase a
* Inactive - phosphorylase b
Converts Glycogen into Glucose-1-phosphate, mobilising the energy source
Phosphatases/kinases recognise a sequence - Serine-14 and (de)phosphorylate it (in)activate it
AMP - low ATP, high AMP means the cell needs more energy
Epinephrine - action needed, energy required,
