Lectures 17/18: Introduction to Metabolism Flashcards
Cellular metabolism (3)
The chemical processes occurring within a living cell or organism that are necessary for maintaining life
- Provide energy, macromolecules, bioactive molecules from intermittent supply of nutrients
- Prevent build up of toxic materials in wrong place
- Breakdown of xenobiotics
Catabolism
Breakdown of large molecules to release energy and small molecules
Of amino acids, monosaccharides and fatty acids: involves oxidizing carbon
Anabolism
Synthesis of large molecules for storage or biomass using energy
Of amino acids, monosaccharides and fatty acids: involves reducing carbon
Macromolecules (3)
- Energy storage (carbohydrates, fat, proteins)
- Energy transport
- Energy release
Oxidation
Loss of electrons from an atom or molecule
The atom/molecule that loses electrons is being oxidized and is an electron donor
Oxidative, exergonic
Reduction
Gain of electrons by an atom/molecule
The atom/molecule that gains the electron is being reduced and is an electron acceptor
Reductive, endergonic
Oxidation state
Most: CO2, carboxylic acid, aldehyde/ketone, hydroxyl, hydrocarbon: least
Most: triple bond, double bond, single bond: least
Highest redox energy yield
Most reduced to most oxidized: full oxidation to CO2 and H2O
Catabolism of fatty acids provides more energy than catabolism of carbohydrates
Metabolic pathways
Interconverted network of metabolites
Several major metabolic pathways share a few common intermediates
Series of sequential reactions, each catalyzed by a specific enzyme
Redox-active cofactor
When a metabolite is oxidized in catabolic reaction, electron is passed on to cofactor (reduced)
Cofactors can be oxidized again by giving up an electron in anabolic reactions
Many derived from vitamins
Includes NAD/NADH, FAD/FADH2, NADP/NADPH, Q/QH2
Oxidation of cofactors
Occurs during anabolic reaction (NADPH) or during oxidative phosphorylation (NADH, FADH2)
Oxidative phosphorylation
NADH and FADH2 are oxidized, oxygen is reduced to water, and ATP is produced
FAD/FADH2
Cofactor that is usually directly complexed to an enzyme
Ubiquinone (Co-enzyme Q)
Cofactor that accepts two electrons in a stepwise manner to become ubiquinol
Essential
A required nutrient that the human body cannot synthesize de novo
The human body cannot synthesize vitamins
Thermodynamics
Energy changes in metabolic pathways
Directionality
Many pathways are overall reversible, but at any given time, only one direction is active
Flux
Rate of overall pathway
Described how many molecules of substrate are converted to product
Controlled through activity of enzymes catalyzing irreversible reactions
Enthalpy
H
Energy
Reaction is favoured if deltaH is negative
Gibbs Free Energy
A reversible process moves spontaneously in the direction that lowers the systems Gibbs’ Free Energy
Entropy
S
Disorder
Reaction is favoured if delta S is positive
Dynamic equilibrium
Rates of the forward and reverse reactions are the same
Nothing changes in the total amount
The concentrations of products and substrates are not necessarily equal
Equilibrium constant Keq
Defined by the concentrations of the reactants and substrates at equilibrium
Inherent property of reaction
Standard Free Energy Change
DeltaG*’ = -RTlnKeq
Described driving force of equilibrium at standard conditions, when all reactants are present at equal concentrations
Set characteristic of a reaction
Actual Free Energy Change
DeltaG= DeltaG*’ + RTln([C][D])/([A][B])
Depends on actual equilibrium concentrations and reflects how far the system is from equilibrium
Spontaneous, favourable systems move towards equilibrium and have a negative deltaG
At equilibrium, deltaG=0
Positive deltaG
Reaction is not spontaneous
Reaction is endergonic and unfavourable
Free energy is required to perform the reaction
Negative deltaG
Reaction is spontaneous
Reaction is exergonic and favourable
Free energy becomes available during the reaction
Unfavourable reactions can be coupled with favourable reactions to make them possible
Exergonic
Energy releasing
DeltaG is negative
Final state is lower energy than starting state
Endergonic
Energy requiring
DeltaG is positive
Final state higher energy than staring state
Often coupled to ATP hydrolysis to make overall reaction favourable and possible
Glucose phosphorylation
Highly unfavourable reaction
DeltaG=+13.8Kj/mol
ATP hydrolysis provides the energy for glucose phosphorylation
DeltaG of each reaction added to give deltaG of coupled reaction
ATP
Energy currency
Drives unfavourable reactions to completion
Made my two exergonic processes: glycolysis and oxidative phosphorylation
Not membrane permeable
Short lived (seconds), must be constantly replenished
Turned over at very high rate
Thioester hydrolysis
To give carboxylic acid ion and CoA-SH
Thioesters have less resonance stability than oxygen esters
Hydrolysis is more exergonic than oxygen ester hydrolysis
Futile cycle
At least one step in a catabolic/anabolic pathway must differ to avoid a futile cycle
All metabolic pathways must be directional and overall irreversible
Directionality is conferred by one or a few irreversible steps
Steady state
Levels and concentrations of metabolites
Does not give information about flux of a reaction
Forward enzyme
Stimulation causes forward reaction
Reverse enzyme is inactive
Reverse enzyme
Stimulation causes reverse reaction
Forward enzyme is inactive
Reversible reactions
Small deltaG
Forwards and reverse rate are similar
Reaction is near equilibrium and cam easily go in either direction: relative ratio of substrate and product determine the direction of the reaction
Increased enzyme activity increases rate of both direction: steady state is reached faster but no change in direction of overall rate
Irreversible reactions
Large deltaG: one side of the reaction is much more stable
Reacts towards products even if there is little substrate available, and changes in reactants have little effects
Forward rate much higher than reverse rate
In metabolic pathways: reverse reaction requires a different enzyme and can have different side products
Homeostasis
Living systems are thermodynamically open and do not reach equilibrium
Work towards maintaining a steady state: flow through system is adjusted so overall system does not change over time
Levels of metabolites are kept relatively constant by adjusting the rates of different pathways
Flus is regulated to maintain homeostasis
