BCA Flashcards
For characterization of drug action, distinguish between?
specificity, selectivity, effectivity.
Effectivity = ?
flux control coefficient pathogen/host
Modular approach (build the model of a very complex system, like glucose metabolism + infection how start?
) by starting with the parasite, isolate, infect red blood cell, stages parasite in red blood cell, multiple reinvasion effect, whole body -> look at different modules, each module revalidate the model. Don’t change the parameter values of original modules.
rules of modular approach?
• Construct and validate models at each of the hierarchical levels:
(enzyme, pathway, parasite, iRBC, iRBC life stages, parasite in
RBC culture, whole body)
• No re-parameterisation after construction/validation
• Use existing models as starting point, model databases and
model annotation, curation, standardisation (Mulquiney, Dalla
Man)
Reduced cost analysis?
which nutrient rate (input) limits output (e.g. growth, product?)
What can you analyze with flux balance analysis? E.g.
> cancer cell flux scenarios (consummation, production)
ATP generation by amino acids
(Growth)Medium design: better understanding of the process
What can you analyze with flux balance analysis? E.g.
> cancer cell flux scenarios (consummation, production)
ATP generation by amino acids
(Growth)Medium design: better understanding of the process
Disadvantage of using the slope to measure the control:
Flux can have multiple units. You could get a unit for the slope but that number would change when you express it in different units.
What you do
change definition that it becomes independent of the unit by changing the change in flux by the relative change in flux (dJ/J) devided by the relative change in enzyme (de/e).dJ/J and de/e then become dimensionless.
This relative slope does not change when expressed per gram protein rather than per gram dryweight.
What is a clever way to figure out the flux control coefficient?
-> activate the enzyme at 1%, ask: what is the % increase in flux? If that is also 1%, then the flux control coefficient C is 1. (1%/1%) If for activation of 1% of the enzyme, the flux changes 0.5%, you get 0.5/1 = C = 0.5. Etc. So, the % change in flux caused by 1% activation of component.
How can one determine a flux control coefficient experimentally?
Modulate the activity of the enzyme and measure the change in flux
How to modulate act of the enzyme?
A) Genetics B) Tunable promoter C) Antisense RNA (but difficult, bc it may target all the RNA) D) In silico computation E) Inhibitor
