Metabolism
Integrated set of enzymatic reactions comprising both of anabolic and catabolic reactions
Anabolism
Synthesis of complex molecules from simpler ones (necessary energy usually derived from ATP)
Catabolism
Breakdown of energy-rich molecules to simpler ones (CO2, H2O and NH3)
Metabolism summary [2]
Anabolism: Synthetic reactions - the pathways end in ‘genesis’
Catabolism: Breakdown reactions - the pathways end in ‘lysis’
Energy required for [4]
- Motion (muscle contraction)
- Transport (of ions/molecules across membranes)
- Biosynthesis of essential metabolites
- Thermoregulation
Free energy
Cells are isothermal systems Heat flow cannot be used as a source of energy (heat can only do work when it passes to an area or an object at a lower temperature) Free energy (energy available to perform work) is acquired from nutrient molecules
Gibbs free energy [3]
- Enthalpy (H): Heat content of the reacting system
- Entropy (S): Randomness or disorder in a system
- Gibbs free energy (G): Energy capable of doing work at constant temperature and pressure
For the reaction A-> B
If the concentration of B > A at equlibrium
- Spontaneous or exergonic reaction
- Free energy is defined as negative DG < 0
- Energy is liberated by the reaction
For the reaction A-> B
If the concentration of A > B at equilibrium
- Unfavourable or endergonic reaction
- Free energy is defined as positive DG> 0
- Energy input is required to start the reaction
Adenosine Triphosphate
- ATP provides most of the free energy required
- ATP is the energy currency of the cell
- Achieved by phosphate group transfer
- Gibbs free energy: The energy derived from the oxidation of dietary fuels
- Energy is conserved as ATP and is transduced into useful work
ATP/ADP Mg2+ complexes [2]
- ATP in the cytosol is present as a complex with Mg2+
- Mg2+ interacts with the oxygens of triphosphate chain making it susceptible to cleavage in the phosphoryl transfer reaction
Substrate level phosphorylation (SLP) [2]
- Formation of ATP by phosphoryl group transfer from a substrate to ADP
- SLPs require soluble enzymes and chemical intermediates
Enzymes [3]
- Biological catalysts that accelerates the rate of chemical reactions
- Creates a new pathway for reactions, one with a lower activation reaction
- Does not influence the Delta G of the reaction
Coenzymes [6]
- Non-protein cofactors - eg metal cation
- Most coenzymes derived from vitamins
- Participate in the enzymatic reaction
- Have a loose association with their enzyme
- Diffuse from one enzyme to the next carry e-
- Regenerated to maintain cellular concentration
Prosthetic groups [3]
- Non-protein cofactor that is covalently bound to the enzyme
- Not released as part of the reaction
- Acts as a temporary store for e- or intermediate
Redox coenzymes/prosthetic groups
[3]
• Major redox coenzymes/prosthetic groups involved in transduction of energy from dietary foods to ATP: NAD+/FAD/FMN
• Electrons are transferred from dietary material to these carriers -> coenzymes are reduced
• In each case two electrons are transferred but the number of H+ moved varies
E.g. NAD+ is reduced to NADH and FAD is reduced to FADH2
Nicotinamide adenine dinucleotide (NAD)
[3]
NAD+ and NADP+ accept pairs of electrons to form NADH and NADPH
Nicotinamide is the functional part of the molecule
• NADH for ATP synthesis
• NADPH for reductive biosynthesis
Re-oxidation of redox coenzymes
• Recycling of NADH and FADH2 is via the respiratory chain in the mitochondria
• This is coupled to ATP synthesis - process of oxidative phosphorylation
~ 2.5 molecules of ATP may be synthesised for 1 NADH re-oxidised [1.5 ATP for every FADH2 ]
Respiration-linked phosphorylation
Respiration-linked phosphorylation involve membrane-bound enzymes and transmembrane gradients of protons and require oxygen
FAD
Prosthetic group derived from from B2- riboflavin
Receives electrons from dietary material to be reduced.
- Receives 2 electrons and 2 protons to form FADH2
- Reoxised in the respiratory chain during oxidative phosphorylation.
FMN
Prosthetic group derived from from B2- riboflavin
NAD+
Co-enzyme derived from vitamin niacin- - Functional group is nicotinamide
Receives electrons from dietary material to be reduced.
- Receives 2 electrons (hydride ion) and 1 proton
- Forms NADH
NADH is reoxidised in oxidative phosphorylation, via the respiratory chain or anaerobic respiration.
NADPH
Reduced NADP
Involved in providing reducing power for reductive biosyntheses
Glycolysis priming stages
- include ATP
- Include enzymes
- Glucose—> G6P (glucose 6-phosphate), hydrolyses ATP.
- uses hexokinase (Hk) - G6P—> F6P (fructose 6-phosphate)
- uses isomerase - F6P—> FBP (fructose 1,6-bisphosphate)
- Uses ATP
- PFK-1 enzyme - FBP —> DHAP, G3P
- aldolase - DHAP—> G3P
- isomerase
G3P continues in glycolysis
What enzyme converts Glucose—> G6P (glucose 6-phosphate)
Hexokinase- HK
This process uses ATP
What enzyme converts
G6P—> F6P (fructose 6-phosphate)
Isomerase
What enzyme converts
F6P—> FBP (fructose 1,6-bisphosphate)
PFK-1
This process uses ATP and is the committed step- cannot be reversed.
What enzyme converts
FBP —> DHAP, G3P
Aldolase
What enzyme can convert DHAP into G3P and vice versa
Isomerase enzyme.
Glycolysis payoff reactions
- Include SLP steps
- NADH formation
- Enzymes
- G3P –> 1,3 BPG (1, 3 biphosphoglycerate).
- G3P dehydrogenase
- NAD+ reduced - 1,3 BPG—> 3PG (3, phosphoglycerate)
- SLP
- PGK enzyme (phosphoglycerate kinase) - 3PG–> 2PG
- mutase - 2PG–> PEP
- PEP —> pyruvate
- pyruvate kinase (Py k)
- SLP
Pyruvate enters link reaction. Payoff reactions happen twice.
What enzyme converts
G3P –> 1,3 BPG (1, 3 biphosphoglycerate)
G3P dehydrogenase
- Forms NADH from NAD+
What enzyme converts
1,3 BPG—> 3PG (3, phosphoglycerate)
PGK (phosphoglycerate kinase)
- SLP step
What enzyme converts
3PG–> 2PG
Mutase
What enzyme converts
PEP —> pyruvate
Pyruvate kinase (Py k)
- SLP step
Why has the system of lactate production evolved?
To recycle NAD+