Lecture 1: Metabolism is the science of energy conversions in living systems.
Adult animals, that are not growing, do not consumeenergy; they convert energy from one form to
another, Ex: Plants convert Sunlight energy to Chemical bond energy. Animals eat plant and convert
chemical bond energy to work. Energy in=energy out.
∗ Organisms store energy during growth. Ex: buildingtissue.
∗ Organisms store energy temporarily during activity.Ex: Convert glucose to ATP which is used to
generate heat and work.
Metabolism is important: 20% of genome used for metabolism. Fuels are degraded and large molecules
are constructed step by step in a series of linkedreactions called metabolic pathways.
Catabolism breaks down fuel, releasing cellular energy
Anabolism requires energy (ex: synthesis of glucose, fats or DNA)
Why do organisms not tend towards disorder?Are we cheating the second law of thermodynamics?
∗ Not all energy is created equal (Joule’s experiment, mass on pulley, potential to thermal energy,
not reversible because energy quality consumed).
∗ Animals convert “higher quality” energy to “lower quality” energy, consuming energy quality.
Living organisms require a continual input of freeenergy for three major purposes:
∗ The performance of mechanical work in muscle contraction
∗ The active transport of molecules and ions
∗ The synthesis of macromolecules and other biomolecules from simple precursors.
Lecture 2: Free Energy, Equilibrium, and Catalysis
The total energy of a system, or Enthalpy, is thetotal energy of a system. The Gibbs free energy
is a measure of the available energy of a system. The entropy of a system is a measure of disorder.
H = Enthalpy
G = Free energy G = H - TS
S = Entropy
⇨ TS indicates the “unavailable” energy.
Universe tends towards disorder, degrading energyquality, releasing Free energy. Hence,
change in free energy determines whether a processis spontaneous. Free energy becomes negative
because entropy must increase.
∆G = ∆G ▯(▯▯▯▯▯▯▯▯) − ∆G ▯(▯▯▯▯▯▯▯▯▯) ∆G = ∆H − T∆S
∆H = 0▯in▯isolated▯system
∆S > 0,∆▯ < 0▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯▯
- Energy can be released to drive a chemical process.
- Standard free energies are additive, and path independent.
Equilibrium: State of minimized Free energy, free energy flows are minimized. Equilibrium is a dynamic
state. Forward rate is equal to the reverse rate ofa reaction at equilibrium.
∗ Forward reaction generally favored if K > 1
Free energies are related to the equilibrium constants!
∆G = −RT▯lnK ▯▯
- Largely negative ∆G result in large changes in K, larger values resultin very small K changes.
- Unfavourable reactions are driven by hydrolysis ofATP, which releases free energy.
∗ ∆G does not determine rate of a reaction! Graphite conversion to diamond is an energetically
favourable reaction, but does not occur readily.
∗ ∆G determines whether a reaction occurs spontaneously.
ΔG < 0 for a spontaneous process
∗ Because catalyst simply lowers the transition stateenergy, it drives both the forward AND the
Free Energy is released during breakdown of glucoseand is used to phosphorylate ADP to ATP. ATP is
used to store energy.
ΔG can be calculated from initial conditions and eq
∆G ▯ = −RT▯lnK ▯▯
∆G = −1362▯logK ▯(▯▯▯▯▯▯▯▯▯▯▯/▯▯▯)
∆G = ∆G + RT▯ln
log (x) = 2.303 ln(x)
R = 1.985 cal K mol How does a process overcome the activation energy?
⇨ The energy of a molecule fluctuates. You can calculate probability that a molecule will make
it over a certain energy state, this can be very low (slow reaction, reaction doesn’t occur)
Cells capture free energy in ATP and release this energy to drive other by coupling.
Thermodynamically unfavorable reactions can be driven by a thermodynamically favorable reaction to
which it is coupled.
⇨ Coupling brings reactions into very close proximity, free energy released by one reaction
drives the other one.
Enzymes catalyze reactions by lowering the free energy oftransition states. TheEnzymes can be
regulated by ATP, which can distort the 3D structure of proteins, thereby modifying their function. (ATP
can induce strain in protein structure).
Km (at ½ V max shows an enzyme’s affinity for its substrate.
The strain can distort the bond and induce bond breakage. It can expose an active site or change the
shape of an active site.
Redox reactions provide a basis for energy transduction --» the oxidation of carbon fuels powers the
formation of ATP. ATP has a high phosphoryl-transfer potential, storing a large amount of free energyin
its bond with phosphate.
Recall: Reduction – Gaining an electron; Oxidation –Losing an electron.
In aerobic organisms, the ultimate electron acceptor in the oxidation of carbon is O and 2he oxidation
product is CO 2.
NAD+ is the principle electron acceptor in
metabolic redox reactions. It carries energy and
transfers it to other molecules. NAD “harvests”
energy, ATP spends it. NAD+ can be used in a wide range of therapies
NAD in tuberculosis is “stuck”, causes a reductionin bacterial cell wall synthesis
The axon decays all the way back to the cell body (in response to injury).
Wallerian-like degeneration is seen in neurodegenerative diseases.
A company that manufactures a mouse withwlds genet hat has delayed degeneration. This
mutation causes an overproduction of NAD+
FAD is used when the available
free energy could not reduce
More free energy is needed for the
reduction of NAD+, FAD is easier
to reduce in comparison.
GAPDH brings NAD+ into position to be reduced. Lecture 4
Polymers broken down into monomeric subunits:
Fats ⇨ Fatty acids and glycerol
Polysaccharides ⇨ Glucose and other sugars
Proteins ⇨ Amino acids
Monomers are taken up through stomach and intestinewalls
and delivered to cells.
Converted into a 2-Carbon carrier (Acetyl group attached to
Goes through Citric acid cycle, 2 CO2 released through an
oxidation reaction, 8 electrons released.
Electrons captured by NAD and transferred to the terminal
electron acceptor, oxygen, , which gets converted to water.
This whole process synthesizes ATP from ADP through
ATP drives energy consuming processes through release of a
Glycolisis: (Occurs in Cytosol)
How glucose is converted to pyruvate, the direct precursor of Acetyl coA.
∗ The part of the glucose breakdown pathway that canoccur in anaerobic conditions is called
glycolisis. Sometimes called fermentation under anaerobic conditions.
∗ In muscle, the end product of fermentation is lactic acid.
∗ In yeast, the end product of fermentation is ethanol
∗ Glycolisis is present in nearly all organisms
Glucose gets converted to pyruvate, when )2 is absent is in converted to Lactate of Ethanol. If Oxigen is
available, Pyruvate enters the citric acid cycle
In vest 2 ATP, recover 4 ATP (2 ATP per pyruvate, 2pyruvate from 1 glucose)
Stage 1: Glucose to Fructose-1,6,-biphosphate
Kinases transpher γ phorphoryl group of ATP to acceptor (sugars in glycolysis)
ATP has a high phosphoryl transfer potential (verynegative free energy change), equilibrium STRONGLY
favours formation of ADP and sugar phosphate.
Glucose-6-phosphate cannot exit
the cell. Phosphorylation of 6th
Carbon "traps" the glucose.
Phosphorilation of Carbon 1 by
which can be broken down into
two 3 C compounds.
***pfk is a pacemaker enzyme.
Both phosphorylations consume
ATP, a total of 2 ATP consumed
per glucose molecule.
Stage 2: Fructose-1,6,-biphosphate cleavage triosephosphate salvage
converted into two 3-Carbon
molecules using Aldolase (Aldol
Half of molecules go directly to GAL3P, other molecules converted to Dihydroxyacetone phosphate,
which gets converted to GAL3P. Stage 3: NADH, ATP and pyruvate generation GAL3P (GAP)
Start off with glyceraldehyde-3-
GAL3P dehydrogenase forms acyl
phosphate. (phosphoryl group on
C=O, has high high phosphoryl
transfer potential, so transfer of that
group to ADP is energetically
Formation of acyl phosphate is
unfavourable, but it is driven by
energetically favourable oxidation of
Phosphoryl group is now on #3
carbon, mutase moves phosphoryl to
#2 carbon, enabling it to form an
enolate, which is an energetically
Pyruvate kinase transfers phosphate