S4- Regulation Of Metabolic Pathways And Glycolysis Flashcards
How are metabolic pathways regulated?
By regulating the enzymes:
- Allosteric regulation
- Product inhibition: intermediates build u p the pathway will slow
- feedback inhibition: downstream products regulate upstream reactions
- hormonal regulation
- high or low energy signals
- feed forward
What is an allosteric site?
Site where another REGULATORY molecule binds that affects catalytic activity- either activation or inhibition
Why are the irreversible steps important to control in pathways and not the reversible steps?
Reversible steps cannot be regulated as they will reach equilibrium even when inhibited
What is the committing step in glycolysis?
PFK- PHosphofructokinase 1
How is PHosphofructokinase-1 regulated?
- Inhibited by:
- High levels of ATP: high energy state, lots of energy, do not need more
- high levels of PEP- stop creating more of me (step 9) - Activated by:
- high levels of ADP and AMP (low level signals)
- increased levels of Fructose-2,6-bisphosphate (F-2,6-BP): high glucose availability, what to reduce that by activating glycolysis by activating PFK1
- HORMONE CONTROLLED
How is hexokinase enzyme regulated in glycolysis?
Inhibited by:
- allosteric regulation (Product inhibition) by glucose-6-P- increased levels of G6P (DONT MAKE MORE!!!)
- inhibited by high NADH concentration (high energy level)
How is the enzyme pyruvate kinase regulated in glycolysis?
- Inhibited by:
- Increased ATP levels: high energy signals - Activated by:
- feedforward: increased levels of fructose-1,6-bisphosphate
Outline the hormonal regulation by insulin and glucagon in glycolysis
Affects enzymes: PFK and pyruvate kinase
INSULIN: has an activating quality
- insulin is released when BGL levels are high, it lowers BGL by activating glycolysis
GLUCAGON: has an inhibition quality
- released when BGL levels are low, increases BGL by inhibiting glycolysis so that less glucose is broken down
Outline how the pyruvate dehydrogenase reaction is:
a) activated
b) inhibited
a) Activated by:
- Pyruvate (the substrate)
- CoASH- co enzyme with free SH group
- NAD+ and ADP –> low energy levels
- Insulin: (released to lower BGL and hence feeds forward)
- dephosphorylation
b) Inhibited by:
- acetyl-CoA (product)
- NADH + ATP –> High energy
- citrate
- phosphorylation
Outline how the TCA is regulated?
Regulated by energy levels:
- Activated; by low energy levels e.g. ADP
- Inhibited: by high energy levels e.g. ATP and NADH
Outline how oxidative phosphorylation is regulated?
INHIBITION:
- High ATP conc/low ADP conc: no susbtrate for ATP synthase
- the conc of H+ in intermitochondrial spcae increases, prevents further h+ pumping, stops e- transport - Inhibition of e- transport e.g. cyanide and carbon monoxide
- blocks flow of electrons (no e- transport) therefore no pmf and no OP (prevents acceptance of electorns by o2)
- lethal - Uncoupling OP from e- transport e.g. dinitrophenol, dinitrocresol, fatty acids (adipose tissue)
- increase permeability of memb to h+
- dissipates proton gradient and reduces PMF
- e- transport able to continue but no OP - OP phosphorylation diseases: genetic defects on proteins encoded by mtDNa
If you were really cold and your body needed extra heat how could your body make use of uncoupling to generate extra heat?
Brown adipose tissue contains a natrually occuring uncoupling protein (thermogenin UCP1)
- when cold noradrenaline activates:
1. Lipase which releases FAs
2. FA oxidation occurs –> NADH/FADH2 –> electron transport
3. FA activate UCP1 (thermogenin)
4. UCP1 transports h+ back into mitochondria, uncoupling e- transport from ATP synthesis
5. the energy from the p.m.f is then released as extra heat
Why is brown adipose tissue found in newborn infants?
- they lose heat very quickly
- brown adipose contains thermogenin UCP1 that releaes extra heat by uncoupling ATP synthesis from electron transport
- the pmf energy released as extra heat
