topic 10 - Metabolism Flashcards
what is metabolism?
Metabolism: chemical processes that occur within an organism to maintain life
- How do cells extract energy from their environment?
- How do cells synthesise the molecules they need?
- How do cells dispose of molecules they don’t need?
This lecture will focus on metabolism of glucose to give ATP – respiration - as an example.
metabolism obeying thermodynamics?
Organisms need to perform actions which are ordinarily energetically unfavourable.
Making/breaking certain bonds
Transporting ions/molecules against a concentration gradient
Large scale motion against gravity/friction.
Use a thermodynamically favourable reaction to drive an unfavourable one
By using a fuel we can remain out-of-equilibrium.
obeying thermodynamics - when can a reaction occur?
A reaction can only occur spontaneously if ΔG is negative.
A B + C ΔG = +20 kJ mol-1 unfavourable
B D ΔG = -32 kJ mol-1 favourable
A C + D ΔG = -12 kJ mol-1 favourable
By coupling the unfavourable reaction to the favourable one, it becomes spontaneous.
Adenosine Triphosphate - ATP
ATP is the energy currency of cells
Removal of either one or two phosphates from ATP to give ADP or AMP yields ca. 30.5 kJ mol-1 under cellular conditions.
This is because breaking the phosphoester bonds reduces electrostatic repulsion
The negative charge is better stabilised in Pi or PPi.
Other phosphates can be more or less prone to transferring a phosphate
ATP has intermediate phosphate transfer potential
This means that it can be regenerated.
what is cellular respiration?
There is about 94 times a much energy in combustion of glucose as is needed to make one molecule of ATP from ADP cellular respiration is how it’s done.
Cytosol –> mitochondrial matrix –> mitochondrial cristae.
what is Glycosis?
- Glucose is phosphorylated. This uses ATP, keeps the sugar within the cell, and prepares it for subsequent reactions. The enzyme in a kinase – kinases transfer phosphate groups.
- The phosphorylated glucose is isomerised to a fructose equivalent. This prepares it for being broken into two C3 fragments.
- The fructose is phosphorylated again, by another kinase, using ATP. The molecule now has two nearly-equal halves.
- The molecule is split in half by a retro-aldol reaction. One half is isomerised to give two molecules of glyceraldehyde-3-phosphate.
- The molecule is oxidised and phosphorylated with consumption of NAD+ and Pi to give NADH. This is equivalent to the phosphate attacking the carbonyl and H- (hydride) acting as a leaving group.
NAD+ is reduced to NADH by accepting the equivalent of H-. It will be reoxidised later.
- There are then two phosphoryl transfers onto ADP to produce two molecules of ATP, with the last giving an enol which equilibrates to the C3 ketone pyruvate
Both the acyl phosphate (1,3-bisphosphoglycerate) and the enol phosphate (phosphoenolpyruvate) have a higher phosphate transfer potential than ATP because their dephosphorylated products have much higher stability.
One molecule of glucose has yielded 4 x ATP, 2 x NADH, and 2 x pyruvate and consumed 2 x ATP
Overall: +2 ATP, +2 NADH, +2 pyruvate
what is the citric acid / Krebs cycle?
- Pyruvate diffuses from the cytosol into the matrix of the mitochondria.
- All fuel molecules (sugars, lipids, amino acids) enter the cycle as Acetyl CoA
what is oxidative phosphorylation?
NADH (and FADH2) produced by the citric acid cycle are subject to oxidation by oxygen:
½ O2 + NADH + H+ H2O + NAD+
ΔG = -217 kJ mol-1
This process is tethered to others to produce ATP.
Electrons from NADH are passed through membrane proteins on the cristae of the mitochondria, pumping H+ out as they go, eventually recombining with O2.
The resultant imbalance of H+ across the membrane is used to drive ATP Synthase as protons flow back in through the protein.
Electrons flow from NADH to O2 through many intermediates
Each step is a small step down in potential, but transports protons across the membrane
This is because protons are removed at oxidative processes which take place on the outer side of the membrane.
oxidative phosphorylation pt 2
There is now a build up of protons in the intermembrane space.
Protons can return to the matrix by passing through ATP synthase
The flow of protons in one direction results in the transmembrane part of ATP synthase to rotate
This results in a sequential change of conformation at the matrix-exposed unit
These changes in conformation ‘squish’ together ADP and Pi to give ATP.
summary of metabolism
Lipids, nucleic acids, proteins, and other small molecules are also synthesised, interconverted, and destroyed by metabolic pathways involving conceptually similar processes.
These processes are interlinked
Enzymes operate at every step
Biology has special reagents e.g. NAD+ for redox
