Regulation of Metabolism Flashcards
Why is metabolic regulation essential for a cell
To prevent all glucose from being used in respiration, ensuring enough is available for biosynthesis (growth, repair, reproduction)
What are the two general strategies cells use to respond to environmental changes
- Regulate gene expression (adjust enzyme amount)
- Regulate enzyme activity (adjust existing enzymes)
What type of regulation is gene expression considered
Slow long term regulation
What is kinetic regulation of metabolism
Adjusting enzyme activity based on substrate and metabolite concentrations — known as mass action
Why is mass action not sufficient for full metabolic regulation
It can’t manage complex decisions like energy vs biosynthesis partitioning
What is ATCase and its role
Aspartate transcarbamylase - involved in pyrimidine biosynthesis, producing CTP
How is ATCase regulated
CTP inhibits ATCase via allosteric binding - a negative feedback loop
Does CTP bind at the active site of ATCase
No, it binds allosterically to the regulatory subunits
What is the kinetic profile of ATCase
It shows sigmoidal kinetics due to cooperativity, not Michaelis-Menten
How many subunits does ATCase have
6 catalytic subunits (2 trimers)
6 regulatory subunits (3 dimers)
Where is the active site of ATCase located
At the interface between catalytic subunits
What are the two states of ATCase
T-state (tense, less active)
R-state (relaxed, more active)
What happens during the T to R state transition
Catalytic subunits rotate, bringing active site residues closer together → more efficient catalysis
What enzyme controls glycolytic flux and how
Phosphofructokinase (PFK) — regulated allosterically
How does ADP affect PFK
Activates it, promoting glycolysis when ATP is low
How does ATP affect PFK
Inhibits it, slowing glycolysis when energy is plentiful
What metabolic problem does PFK regulation help solve
The energy vs carbon skeleton partitioning problem
How can enzyme organisation regulate metabolism
Enzymes can cluster to form complexes, increasing reaction speed by concentrating substrates/intermediates
What is a common post-translational modification for enzyme regulation
Phosphorylation
What enzymes control phosphorylation states
Kinases add phosphate groups
Phosphatases remove them
What are four key reasons phosphorylation is effective for regulation
- Adds two negative charges + 3+ H-bonds → alters protein conformation
- Can occur in seconds or hours
- Amplifies signals (1 kinase → 100s of targets)
- Uses ATP, linking it to cellular energy status
How does phosphorylation affect enzyme structure
It changes the shape of the active site or the overall enzyme conformation, influencing activity
What is the main difference between genetic and kinetic regulation of metabolism
Genetic regulation changes the amount of enzyme produced (slower, long-term)
Kinetic regulation modifies the activity of existing enzymes (faster, short-term)
What determines whether glucose enters glycolysis for ATP or biosynthetic pathways
The cell’s energy status, signalled by ADP/ATP levels, and controlled via allosteric regulation (e.g. of PFK)