L7: Energy Production- Carbohydrates- Regulation of metabolic pathways Flashcards
How can metabolic pathways be regulated?
Allosteric regulation Covalent modification Metabolic regulation Product Inhibition Committing step Hormonal regulation
What is meant by allosteric regulation?
An activator or inhibitor that bind at another site not the enzyme active site
Binds to the regulatory site affecting the catalytic abilities
What is meant by covalent modification?
Phosphorylation and dephosphorylation
Kinases and phosphatases
Introduction of bulky negatively charged PO42- moiety
Adds structure (protein conformation), alters activity
What is flux?
Rate of turnover of molecules through a metabolic pathway
How does flux help with regulation of metabolic pathways?
Pathway is regulated in response to need
Only running when required
What are the potential sites for regulation in a metabolic pathway?
Irreversible step
→ reduced activity of this step reduces the flux of substrates through a pathway
→ Reducing levels of product
Reversible steps are not regulated→ will reach an equilibrium
How does product inhibition work?
A product of a reaction feeds back on a step earlier on in the pathway preventing flow through the pathway
Often final product inhibits first enzyme, preventing substrates entering the pathway
e.g. ↑[C] the B↔C will be displaced, more of B will be produced, rate of binding of B to enzymes will decrease, reduce rate of catalysis of B to C, as pathway intermediates build up flux through pathway will slow
What is the committing step?
Step in a pathway that once the substrate has passed it it is committed to that pathway
Inhibition of committing step allows substrate to be diverted into other pathways
How does metabolic regulation work?
Regulation of key enzymes in a pathway Inhibited by high energy states → ATP, NADPH, NADH, FADH2 Activated by low energy states → ADP, AMP, NAD+, FAD
What is hormonal regulation?
Hormone receptor binding
Activates signalling pathway
Alters protein conformation/activity positively or negatively depending on the target enzyme
e.g. protein kinase (phosphorylation) or protein phosphatase (dephosphorylation)
What is feed forward regulation?
Early pathway substrates provides positive allosteric signal to stimulate a later enzyme to activate the pathway
Give some examples of when phosphoregulation?
Insulin
→ Stimulated signalling pathway activates protein phosphatase 1
→ Dephosphorylates/ activates pyruvate dehydrogenase
- Stimulates glucose utilisation
→Dephosphorylates glycogen phosphorylase
- Inhibits glycogen breakdown
What are the key regulators of glycolysis?
Phosphofructokinase-1
NADH/ NAD+
Phosphoregulation
Hexokinase
How does phosphofructokinase-1 regulate glycolysis?
Step 3
Key enzyme in committing step
Allosteric regulation
→ ↑[ATP] ↓[AMP] inhibited, cell in high energy state
→ ↓[ATP] ↑ [AMP] activate, cell in low energy state
Hormonal
→ Insulin activates, well fed lots of glucose
→ Glucagon inhibits, starvation mode, prevent glucose breakdown
How do the levels of NADH/ NAD+ affect glycolysis?
Main affect on Step 6
↑ NADH/NAD+ ratio cells in high energy state, inhibit glycolysis
↓ NADH/ NAD+ ratio cells in low energy state, activate glycolysis
