University of Cambridge
Biochemistry Part 1A
Lecture Series: Bioenergetics and Metabolism
Lecture 1:
One reaction can be coupled to another to drive a thermodynamically unfavourable reaction
Gibbs free energy change = same despite pathway way unlike Hess’s law
Second Law Thermodynamics = entropy tends to increase, cells cheat this to make complex
macromolecules.
At equilibrium ∆G= - RT ln(Keq)
Keq = exp(-∆G/RT)
Coupling reactions: multiply equilibrium constants
Under typical cellular conditions ∆G ~ –50 kJ mol -1 for ATP hydrolysis (concentration also
plays a part).
∆G = ∆G°′ + RT ln {Keq}
∆G = –30.5 kJ mol-1 + RT ln {[ADP][Pi][H+]/[ATP][H2O]}
Pi and ADP have more resonance stabilization as negative charge spread
Electrostatic repulsion, at pH 7, four – close
Stabilization by hydration, enthalpically and entropically fav
High phosphorylation potential of PEP, 1,3-BPG, PCr
Measure ATP changes using 31P NMR spectroscopy
Forming dipeptides
Joining nucleotides in DNA synthesis
Activated carriers drive thermodynamically unfavourable reactions:
Biotin carries CO2
NADP+ for biosynthesis, provides two redox potentials one for ATP production and
another for other metabolites
CoA-SH high energy Sulphur bonds: carries acetate, acyls. Hydrolysis ACA = -
31.5kJ/mol
Why control metabolic pathways:
Avoid futile cycles
Link energy production to usage
Respond to physiological changes
How are enzyme amounts controlled?
, Rate of synthesis, transcription factors
Rate of destruction
Metabolic control of enzymes: rapid. Feedback inhibition from product, preventing build-up
of intermediates
Mechanisms for controlling enzyme reaction rates:
Allosteric, changes affinity for substrate, intracellular signals
Covalent, phosphorylation from ATP causes conform change, slower, regulated by
hormones
Lecture 2: Carb Metabolism
Glut 1,2,3 in brain, liver and erythrocytes are insulin-independent. Directly proportional
blood glucose = rate of transport. More sensitive
Glut 4, muscle and fat, insulin-dependent. Trapped in vesicles that fuse with PM. T2D
transporter not in right place only 10% on PM. Kinase activity increases transport to PM
AKT2, RAB-GTP
Glycolysis produces net +2 ATP, +2NADH (mitochondria, reduce pyruvate to lactate)
Can be used to produce energy anaerobically
RBC, retina don’t have mitochondria
Fast twitch muscles
Oxygen debt repaid by increasing citric acid cycle to oxidise lactate
Irreversible changes, with large change in ∆G. Controlled by allosteric modification of
enzymes.
G >> G6P by hexokinase/glucokinase
F6P >> F1,6BP by PFK1
Phosphoenolpyruvate >> Pyruvate by pyruvate kinase
Dysregulation causes: Neurodegenerative, Amplification of ischaemic damage and cancer
proliferation as transcription increased so cells have competitive adv. over host
, Lysis consumes 2 ATP per glucose
Oxidation produces net 2 ATP and 2 NADH per glucose. CHO to COOH energetically more
favourable. Oxygen from water. Oxidizing agent is NAD +
Rearrangement produces 2 ATP per glucose. Energy to phosphorylate from replacing C=C to
C=O
Biochemistry Part 1A
Lecture Series: Bioenergetics and Metabolism
Lecture 1:
One reaction can be coupled to another to drive a thermodynamically unfavourable reaction
Gibbs free energy change = same despite pathway way unlike Hess’s law
Second Law Thermodynamics = entropy tends to increase, cells cheat this to make complex
macromolecules.
At equilibrium ∆G= - RT ln(Keq)
Keq = exp(-∆G/RT)
Coupling reactions: multiply equilibrium constants
Under typical cellular conditions ∆G ~ –50 kJ mol -1 for ATP hydrolysis (concentration also
plays a part).
∆G = ∆G°′ + RT ln {Keq}
∆G = –30.5 kJ mol-1 + RT ln {[ADP][Pi][H+]/[ATP][H2O]}
Pi and ADP have more resonance stabilization as negative charge spread
Electrostatic repulsion, at pH 7, four – close
Stabilization by hydration, enthalpically and entropically fav
High phosphorylation potential of PEP, 1,3-BPG, PCr
Measure ATP changes using 31P NMR spectroscopy
Forming dipeptides
Joining nucleotides in DNA synthesis
Activated carriers drive thermodynamically unfavourable reactions:
Biotin carries CO2
NADP+ for biosynthesis, provides two redox potentials one for ATP production and
another for other metabolites
CoA-SH high energy Sulphur bonds: carries acetate, acyls. Hydrolysis ACA = -
31.5kJ/mol
Why control metabolic pathways:
Avoid futile cycles
Link energy production to usage
Respond to physiological changes
How are enzyme amounts controlled?
, Rate of synthesis, transcription factors
Rate of destruction
Metabolic control of enzymes: rapid. Feedback inhibition from product, preventing build-up
of intermediates
Mechanisms for controlling enzyme reaction rates:
Allosteric, changes affinity for substrate, intracellular signals
Covalent, phosphorylation from ATP causes conform change, slower, regulated by
hormones
Lecture 2: Carb Metabolism
Glut 1,2,3 in brain, liver and erythrocytes are insulin-independent. Directly proportional
blood glucose = rate of transport. More sensitive
Glut 4, muscle and fat, insulin-dependent. Trapped in vesicles that fuse with PM. T2D
transporter not in right place only 10% on PM. Kinase activity increases transport to PM
AKT2, RAB-GTP
Glycolysis produces net +2 ATP, +2NADH (mitochondria, reduce pyruvate to lactate)
Can be used to produce energy anaerobically
RBC, retina don’t have mitochondria
Fast twitch muscles
Oxygen debt repaid by increasing citric acid cycle to oxidise lactate
Irreversible changes, with large change in ∆G. Controlled by allosteric modification of
enzymes.
G >> G6P by hexokinase/glucokinase
F6P >> F1,6BP by PFK1
Phosphoenolpyruvate >> Pyruvate by pyruvate kinase
Dysregulation causes: Neurodegenerative, Amplification of ischaemic damage and cancer
proliferation as transcription increased so cells have competitive adv. over host
, Lysis consumes 2 ATP per glucose
Oxidation produces net 2 ATP and 2 NADH per glucose. CHO to COOH energetically more
favourable. Oxygen from water. Oxidizing agent is NAD +
Rearrangement produces 2 ATP per glucose. Energy to phosphorylate from replacing C=C to
C=O
