Metabolism and

Bioenergetics

A Angeles
Chem 40
 Metabolism and Bioenergetics

• Classification of living organisms according to carbon

sourcing from the environment:
 Metabolism and Bioenergetics

• Classification of living organisms according to

energy source:
– Phototrophs: photosynthetic organisms that use light as
a source of energy
– Chemotrophs: use organic compounds (e.g. glucose) or
oxidizable inorganic substances (e.g. elemental sulfur,
Fe2+, or NH4+).
• Energy is typically extracted using redox reactions.
 Metabolism and Bioenergetics

• Classification of living organisms according to the role

of O2 in metabolism:
– Aerobes can utilize O2 as an electron acceptor
• Obligate aerobes: O2 is an absolute necessity
• Facultative anaerobes: normally use O2 but can adapt to
anaerobic conditions by using other compounds as an
electron acceptor
– Anaerobes can perform oxidation reactions to
release energy without using O2 as an electron
acceptor
• Obligate anaerobe: must have anaerobic conditions
(oxygen is a poison)
 Metabolism and Bioenergetics

• Metabolism is the overall process through

which living systems acquire and use free
energy to drive their growth and function.
– Catabolism: degradation of nutrients and cell
constituents to generate energy or salvage their
components
– Anabolism: energy-requiring biosynthesis of molecules
from simpler precursors
Metabolism and Bioenergetics
• Energy is released
through the formation
of ATP, reduction of
electron carriers and
heat.
 Metabolism and Bioenergetics

• Although catabolic and anabolic pathways utilize

common enzymes and substrates, they are NOT
reversible.
– At least one step is catalyzed differently
– At least one step is thermodynamically favourable
– Contrasting pathways are compartmentalized in the cell
(e.g., fatty acid metabolism)
– As a result, catabolic and anabolic processes are
regulated independently.
 Metabolism and Bioenergetics

• More on metabolic pathways…

– Every metabolic pathway has a first committed
step (i.e., highly exergonic process)
– Catabolic and anabolic pathways differ
 Laws of Thermodynamics

• The First Law
for any change, the energy of the universe
remains constant; energy may change form or it may be
transported, but can not be created or destroyed
• The Second Law
can be stated as follows
– Systems tend to go from an ordered to a disordered state.
– Entropy can remain the same for reversible processes but
increases from irreversible processes.
– All processes tend towards equilibrium.
• equilibrium = death
• The Third Law
entropy goes to zero when ordered
substances approach absolute zero = 0oK
 Thermodynamics

• Gibbs Free Energy: G and 6G

• Enthalpy: H and 6H
• Entropy: S and 6S
%G = %H-T %S
 Metabolism and Bioenergetics

Hydrolysis of acid anhydride-type molecules and complete

oxidation of organic compounds result in a large decrease in free
energy.
 Metabolism and Bioenergetics

6Go’ are additive

Hexokinase:
Glucose + ATP

Glucose-6-P + ADP
Glucose + Pi
Glucose-P + H2O; 6Go’ = 13.8 kJ/mole
ATP + H2O
ADP + Pi; 6Go’ = -30.5 kJ/mole
Overall = 6Go’ = -16.7 kJ/mole
Exergonic !

Thus it is possible to actualize unfavorable processes given that there

is a coupled reaction which can provide free energy.
ATP as the Energy Currency
ATP as the Energy Currency
2 phosphoanhydride
bonds
 ATP as the Energy Currency

• Mg2+ further weakens bonds in the highly negative

phosphate moieties of ATP and ADP.
 ATP as the Energy Currency

• Calculate 6G for the hydrolysis of ATP to ADP in a human

erythrocyte.
 Metabolism and Bioenergetics

• How do living organisms synthesize ATP?

– It can be regenerated by coupling its formation to a more
highly exergonic metabolic process
– Substrate level phosphorylation
– Oxidative level phosphorylation
– Photophosphorylation (in plants)
 Substrate level
phosphorylation

• ATP synthesis can be

coupled with the
phosphate hydrolysis of
‘higher-energy’
molecules
Substrate level phosphorylation
 Oxidative level phosphorylation

• ATP synthesis is brought about by energy released

through a series of electron transports (redox
reactions)
– Cell must have a respiratory system
• Prokaryotes
ETC found in cytoplasmic membrane
• Eukaryotes sans plants
ETC found in the inner mitochondrial
membrane
• Plants
ETC found in the inner membrane of chloroplast
(photophosphorylation)
– O2 must be available (for heterotrophs); O2 is reduced to
H2 O
 Oxidative level phosphorylation

• The following occurs during the electron-transport

process:
– NADH and FADH2 are reoxidized to NAD+ and FAD,
respectively, as they pass on electrons to other electron
carriers in the chain
– The electrons introduced are passed sequentially in four
enzyme complexes until ultimately reducing O2 to H2O
– In the process of the electron transfer, protons (H+) are
pumped into the intermembrane space of mitochondrion,
creating a proton gradient
the stored energy drives
synthesis of ATP from ADP and Pi
Oxidative level phosphorylation
Oxidative level phosphorylation
Oxidative level phosphorylation
Oxidative level phosphorylation
(+) values indicate
favourable
reduction

(-) values indicate

unfavourable
reduction
 The Electron Transport Chain

• Electron transport is an exergonic process

Recall: 6Go = -nF6εo
6εo = εored – εoox

Compute for the free-energy associated with the

oxidation of NADH to NAD+ and reduction of O2 to
H2O.
 The Electron Transport Chain

NADH and FADH2

bring electrons to
ETC
– Subsequently,
electrons are
passed between
redox centers in
increasing reduction
potentials
The Electron Transport Chain

Reduction potentials
intermediate of
NAD+ and O2
 The Chemiosmotic Theory

• The chemiosmotic theory (Peter Mitchell, 1961)

links the electron transport chain to ATP synthesis
 ATP Synthase

• The ATP Synthase (Complex V)

– Proton-pumping ATP synthase or F1Fo-ATPase
– 2 components: F1
peripheral membrane
protein; Fo
transmembrane protein
• The influx of protons through the Fo
component drives the F1 component to
synthesize ATP from ADP and Pi via binding
change mechanism
ATP Synthase
 ATP Synthase

• The binding change mechanism at F1

– L
Loose; holds substrates and product
– T
Tight; catalyzes the formation of ATP
– O
Open; releases the product

– The three conformations cycle through rotation of F1

Oxidative level phosphorylation
 Oxidative level phosphorylation

• Oxidative phosphorylation requires an intact inner

mitochondrial membrane.
• The inner mitochondrial membrane is impermeable
to ions such as H+, OH-, K+, and Cl-, whose free
diffusion would discharge an electrochemical
gradient.
• Compounds that increase the permeability of the
inner mitochondrial membrane to protons inhibit ATP
synthesis.
• Increasing the acidity outside the inner mitochondrial
membrane stimulates ATP synthesis.
 Oxidative level
phosphorylation

Examples of uncouplers
Oxidative level phosphorylation
 Oxidative level
phosphorylation

An in vitro experiment
that validates the
chemiosmotic theory
 Oxidative level phosphorylation

• P/O ratios
– NADH: 2.5
– FADH2:1.5