1. Regulatory Strategies Flashcards
Why must all cells regulate their metabolism?
To meet basic requirements (energy, carbon, nitrogen, minerals) and to respond to changing external conditions (carbon, solutes, pH)
What is the concentration of the solute compare to enzymes in the intracellular environment?
Equal
What two types of substrate are there? Where may they be present?
Hydrophilic substrate - may only cross membranes via transporter proteins
Hydrophobic substrates - associate with membranes/binding proteins/lipid droplets
Which coenzymes are conserved?
NADH, NADPH, ATP, GTP, FADH2
What is the equation for the energy charge of a cell? Give a rough estimate of an average cell energy charge.
[ATP]+0.5[ADP]/[ATP]+[ADP]+[AMP]
0.9-0.95
EC may go from 0-1
Why is it important for the ratios of the forms of conserved metabolites to be maintained within trick limits?
The changing ratio will affect the direction of reactions. To avoid this, any deviation from ideal ratios stimulates the cell to implement measures to equalise.
What methods may cells use to regulate their internal processes (4)? Keeping the conserved metabolite ratio the same.
- Take up different substrates (altering transport proteins)
- Halt uptake of other substrates
- Process different substrates (alter metabolic pathways)
- Synthesise new substances (that aren’t available in surrounding)
In multicellular organisms the external environment (of the cells) is usually kept constant, so why may cells deliberately alter substrate availability? Give an example
In order to support changes in metabolism of other cells, or to spare substrates for other tissues
e.g. Some tissues internalise glucose transporters in the fasting state, and adipose increases fatty acid release
What 7 ways may proteins be regulated?
- Transcription
- mRNA stability
- Translation
- Degradation
- Location
- Allosteric Control
- Covalent modification
How does protein regulation through transcription occur?
Control of which genes are transcribed - vary in different conditions
How does protein regulation occur through mRNA stability?
The rate at which mRNA is degraded is regulated - so longer lasting mRNAs can transcribe more proteins (and vice versa)
How does protein regulation occur through degradation?
Proteins may be tagged by ubiquitin and degraded by 26S proteasomes
OR
Broken down in lysosomes
How will halting the degradation of a protein with a short half life vary its concentration compared to halting the degradation of a long half lie protein?
Short half life will quickly increase concentration whereas the long half life will increase concentration but much slower
How does the location of the protein affect its efficacy? Roughly how long does it take to for a protein to be moved?
Protein must be in the right location to work. This takes seconds-minutes (quick)
What is allosteric control? How fast does this control protein levels?
Allosteric control is the reversible, non-covalent binding of effectors to enzymes resulting in activation or inhibition.
milliseconds-seconds
What is the difference between the T state and the R state?
T (tense) star does not allow the substrate to bind well, whereas the R (relaxed) state binds substrate easily
In allosteric control, what is the relationship between v0 and [S] if the substrate binds and stabilises the R-state of the oligomeric protein? What does this mean for the sensitivity of the enzyme/protein?
There is a sigmoidal relationship between v0 and [S].
The steep gradient of the sigmoidal curve (at some points) means there is a large variation in v0 for small variation in [S], meaning that the protein is very sensitive to changes in [S]
What is the difference between competitive, non-competitive and uncompetitive inhibitors? How may these affect the Km and Vmax of the enzyme they are bound to?
Competitive: Binds to the active site, increases Km, Vmax constant
Non-competitive: Binds away from active site of E and E:S complexes, decreases Vmax, Km remains the same
Uncompetitive: Binds E:S complex away from active site, Vmax decreases, Km decreases
What two types of effector are there?
Homotropic (if effector is enzymes substrate/product) and heterotropic
How does covalent modification of proteins occur? What modifications may be made? How fast does this occur?
Enzyme catalysed (stable)
Phosphorylation, Adenylation, ADP-Ribosylation, methylation
Seconds-minutes
Which amino acids may be phosphorylated?
Serine, Threonine and Tyrosine (on the hydroxyl groups)
Which enzymes is phosphorylation catalysed by? Which enzyme catalyse dephosphorylation?
(Protein) Kinases phosphorylate
(Phosphoprotein) phosphatase dephosphorylates
What does phosphorylation do to proteins?
Activate or inhibit them
What kind of reactions do rate-limiting enzymes catalyse? Where are regulatory enzymes typically placed on an enzyme pathway? Why?
These enzymes catalyse reactions where cellular concentrations are far from equilibrium. Reactions are usually exothermic and irreversible.
Just after branch points, ensuring that the pathway is ‘committed’
What is the flux control coefficient? What is it’s symbol? How may it be calculated?
Defines which enzymes contribute the most towards pathway control
C
Experimentally determined (may change depending on circs.)
What do the C values for a pathway always add up to?
1
