The reaction can run in both directions depending on conditions
At equilibrium, there is no net reaction. i.e. forward and reverse reaction are at the same speed.
Laws of thermodynamics state the energy cannot be created nor destroyed and can only be converted into other forms.
This helps to predict if a reaction is possible and how much energy will required or released
Gibbs Free Energy
ENERGY AVAILABLE TO DO WORK
DeltaG - Change in free energy as the reaction occurs. Not constant. Dependant on standard free energy change, concentration of reactants and temperature.
DeltaG°' - Standard free energy change when the reaction is conducted in a standard state at pH 7.0 at 25 degrees and 1 atm, when the concentration of reactants is 1.0M.
Has a characteristic constant value for a given reaction.
If DeltaG is negative - a reaction proceeds spontaneously and with a loss of free energy. The reaction is EXERGONIC
If DeltaG is positive - the reaction is unfavourable or un-spontaneous. The reaction is ENDERGONIC. (The reverse reaction is spontaneous)
If DeltaG = 0 - no free energy change takes place, the system is at equilibrium.
- Release energy
- Catabolism of food
- Require energy
- Synthesis of biomolecule
- Muscle contraction
- Nervous excitation
- Active transport
Adenosine Triphosphate (ATP)
Principal high energy phosphate intermediate in living cells and plays a key role in energy transfer and captureb.
ATP is a nucleoside - same structure in all organisms
1 adenine (nucleotide base) linked to 1 ribose (5-C sugar) linked to chain of 3 phosphate groups
ADP: Adenosine Diphosphate (2 phosphate groups)
AMP: Adenosine Monophosphate (1 phosphate group)
ATP + H2O ADP + Pi + H+ DGo’ = -31 kJ/mol
ADP + Pi + H+ ATP + H2O DGo’ = +31 kJ/mol
- In cells ATP and ADP concentrations vary and are hard to measure hence free energy can only be estimated
- Reactions releasing energy are indirectly coupled to synthesis of ATP from ADP + Pi
- Reactions requiring energy are made favourable my coupling to the breakdown of ATP to ADP + Pi
- Energy released allows reaction to proceed
General Rule for ATP
ATP acts as a donor of high energy phosphate to compounds below it in free energy levels.
ATP formed from ADP by accepting a phosphate group (PO4) from compounds above it in free energy levels
Phosphorylation for Energy
Mechanisms exist for organisms to transfer energy from reactions to form ATP via:
- Substrate Level Phosphorylation
- Oxidative Phosphorylation
- Photophosphorylation (photosynthesis)
Substrate Level Phosphorylation
Substrate "X" (high energy compound) + ADP ====> Compound "Y" + ATP
PEP (phosphoenolpyruvate) + ADP ===> ATP + Pyruvate
The production of ATP from ADP by a direct transfer of a high-energy phosphate group from a phosphorylated intermediate metabolic compound in an exergonic catabolic pathway
Oxidation = loss of electrons
Example: Electron Transport Chain
- Reduced coenzymes are H+ and electron carriers that feet into the Electron Transport System (ETS).
- Transfer of protons and electrons allow for the formation of ATP via oxidative phosphorylation
- Examples include: NAD+/NADH and FAD/FADH2
What is Metabolism?
Total of all the chemical reactions taking place in a cel
Reactions are organised into pathways
Metabolites are formed in pathways are are small molecules that are produced in the degradation or biosynthesis of biopolymers.
Process devoted to the degradation of complex substance into smaller simpler molecules.
Process concerned with the synthesis of complex organic substance from smaller simpler ones.
Pathways occur as multiple reaction steps
These result in intermediates that cross into other pathways
Specific enzymes will break down an overall reaction into different steps to maximise the production of energy.
Energy is conserved by the production of ATP and reduced co-enzymes.
Features of Metabolism
Common steps can be found in anabolic and catabolic pathways.
Difference lie in key reactions where different enzymes are used to reverse the direction of the pathway.
Control points are often at the beginning of a pathway or at crossover points. Often function via a feeback mechanism.
Cellular Respiration - Glycolysis
Three phases of cellular respiration:
- Glycolysis (anaerobic)
- Citric acid (Krebs) cycle (aerobic)
- Electron Transport & Oxidative Phosphorylation (aerobic)
Glycolysis - sequence of reactions converting glycose into pyruvate.
Site of Glycolysis - the Cytosol
Glycolysis in 2 stages:
- Conversion of glucose to fructose 1,6-bisphosphate (followed by cleavage to form glyceraldehyde-3-P) An energy 'investment stage' - ATP utilised.
- Conversion of glyceraldehyde-3-P to pyruvate. An energy 'pay out stage' - ATP produced
Significance of energy 'investment stage'
Energy requiring reaction - provided by ATP
Glucose becomes phosphorylated
Cannot diffuse out of the cell - 'fixed'
First committed step of pathway
Reactin catalysed by two different enzymes
Found in all cells
Functions to ensure supply of glucose to tissues even in low glucose concentrations
Ensures large glucose gradient maintained between blood and intracellular environment
Has high affinity (low Km) for glucose
Allosteric enzyme inhibited by G-6-P
Only found in liver and pancrease
Removes glucose from blood following a meal
Has low affinity for glucose (high Km)
Stage One - Isomerisation
GLUCOSE-6-PHOSPHATE (HEXOALDOSE) <==> FRUCTOSE-6-PHOSPHATE (HEXOKETOSE)
Purpose of glycolysis - split glucose into two 3C compounds
Requires aldol split to form an aldehyde and a ketone
Glucose does not have the correct structure for the split but fructose does and therefore G-6-P is converted to Fructose-6-P
Stage One - Further Phosphorylation
FRUCTOSE-6-PHOSPHATE ==(ATP==>ADP)==> FRUCTOSE-1,6-BISPHOSPHATE
Reaction is catalysed by enzyme phosphofructokinase (PFK)
PFK is an allosteric enzyme regulated by ATP levels
High ATP levels - PFK inhibited
Levels of G-6-P increase, hexokinase also becomes inhibited
Mechanism prevents all glucose being used in repsiration
Allows diversion into other pathways
Low ATP levels (high AMP levels) - PFK reactivated
Hexokinase also reactivated - glycolysis restarts
PFK also inhibited by phosphoenolpyruvate and citrate
Stage Two - Further Phosphorylation
GLYCERALDEYHYDE-3-P ==(NAD++Pi=>NADH)==> 1,3-BISPHOSPHOGLYCERATE
The reaction is catalysed by glyceraldehyse-3-P dehydrogenase
The reaction generates NADH that will feel into electron transport.
Stage Two - Dephosphorylation
1,3,-BISPHOSPHOGLYCERATE ==(ADP==>ATP)==> 3-PHOSPHOGLYCERATE
The reaction is catalysed by phosphoglycerate kinase
Removal of the phosphate groups results in a release of energy, captured by formation of ATP - an example of substrate level phosphorylation
Transfer of a Phosphoryl Group
3-PHOSPHOGLYCERATE <====> 2-PHOSPHOGLYCERATE
Reaction is catalysed by phosphoglycerate mutase
Intramolecular transfer of the phosphoryl group prepares the moelcule for the final stages of glycolysis.
Dehydration and redistribution of energy
2-PHOSPHOGLYCERATE <=====> PHOSPHOENOLPYRUVATE (PEP) + H2O
Reaction catalysed by enolase
The penultimate step redistributes energy to produce a high energy phosphate, phosphoenolpyruvate (PEP)
Generation of Pyruvate
PEP ====(ADP==>ATP)===> PYRUVATE
Reaction catalysed by pyruvate kinase
Transfer of the phosphate group from PEP to generate pyruvate releases energy as ATP (substrate level phosphorylation)
ATP Production in Glycolysis
- 2 molecules ATP are used to form F-1,6-bisP
- 4 moleules ATP generated (2 for each G-3-P)
NET GAIN OF ATP = 2 MOLECULES
2 NADH GENERATED
What happens next?
If oxygen is absent: anaerobic conditions, fermentation or lactate formation
If oxygen is present - aerobic conditions, further oxidation and more energy captured in the citric acid cycle and electron transport chain.