Metabolic Network

Question 1

Metabolism

Answer 1

the set of life-sustaining chemical transformation within the cell organisms
Purpose metabolism:
Extraction of energy, storage of fuels, synthesis (proteins, lipids, nucleic acid, carbohydrate), elimination of waste
Components:
connected reaction= production of one is substrate of next
Catalyzed by enzymes
Activity tuned according to immediate needs
Coordinate series of chemical reactions
Goal is to create or breakdown a molecule

Question 2

Glycolysis to ATP

Answer 2

Glycolysis: glucose to pyruvate
Krebs Cycle/ TCA cycle: (pyruvate to citrate), citrate to ATP
LDH
ATP to ADP by hydrolysis (water slip off negatively charged bounds), this release energy

Question 3

Metabolism network

Answer 3

nodes: metabolites
edges: reactions
Genome scale: many parameters, extensive data -> infeasible for most metabolic network. Gene expression allows to construct network for specific cell type -> map data : constrained.
Study:
network connectivity (on log scale: some metabolites participate to thousands reactions others in a few)
reaction rate: fluxes, how much product produced per time -> fluxes can be function of time: dynamic modeling, how much is consumed, concentrations, etc

Question 4

Mendelian disease/ ordinary disease

Answer 4

Mendelian disease: affect a single gene/enzyme

Ordinary disease: many deficiencies in network (not all lead to disease)

Question 5

Metabolic fluxed modeling

Answer 5

v1,v2,… reaction rates/fluxes. Reaction irreversible if directed to one direction
Constrained solution space: upper/lower bounds on reactions -> uptake. Solution space gives max possible value
Steady state: each metabolite has constant concentration. Will lead to a constant state vector
Only stoichiomestry is required to predict steady states
Mass balance: v_production - v_consumption = 0
Steady state based on mass balance constraint: constraint based modeling
Can find optimal steady state to optimize production

Question 6

Stoichiometric matrix

Answer 6

Contains structure of network
Column: stochiometry of 1 reaction
rows: metabolites consumed/produced
-k if consumed by reaction k times
\+k if produced by reaction k times

Question 7

mass balance equation

Answer 7

for each metabolites: reaction production=reaction consumption

Question 8

Flux balance analysis

Answer 8

Predicting flux steady state by maximizing objective function

Question 9

Warburg effect

Answer 9

Cancer: high rate of glycolysis and lactic acid fermentation even with O2. Pyruvate to Lactate ! As if anaerobic
Normal: pyruvate to lactate and lactate back to pyruvate. Then pyruvate to TCA cycle and OXPHOS. ATP!

Question 10

Cancer metabolic network

Answer 10

Remove gene not expressed -> proteins produced will also be low expressed