Cellular Metabolism

Introduction
• Cells capture and utilize energy through a
series of chemical reactions which involve:
a) Rearrangement of electrons within molecules
involved in the reaction
b) Redistribution of energy these molecules
contain
Some molecules end up with more energy than
they began with, some less.
 Introduction
• The complex network of reactions inside the
cell captures the energy and raw materials of
its surroundings and allow them to be
changed into forms that are used to sustain
cells
• This network of reactions is called
metabolism.
 Energy Change in Chemical Reactions

• All chemical reactions are accompanied by a

net energy change.
• The value of this energy change depends on
how much energy is taken in by the chemicals
when chemical bonds form and how much
energy is released when bonds break.
 Energy Change in Chemical Reactions

• In chemical reactions, there is a balance

between
a) Energy taken when chemical bonds break
b) Energy released when chemical bonds form
c) Energy exchanged with surroundings
• In totality, there is an overall loss of usable
energy in cells.
 Energy Change in Chemical Reactions

• Change in free energy ΔG – change in usable

energy available to do work
Positive ΔG – Reaction will not proceed
spontaneously. It is work requiring. Endergonic
Negative ΔG – Reaction will proceed
spontaneously. It is work producing. Exergonic
Recall: ΔG = ΔH - TΔS
 Energetics of Cellular Metabolism
• Free energy released in exergonic reactions
can be used to drive endergonic reactions.
Ex.
Rxn 1: ΔG1 < 0 (exergonic)
Rxn 2: ΔG2 > 0 (endergonic)
Overall reaction ΔG = ΔG1 + ΔG2
When |ΔG1| > |ΔG2|, ΔG < 0 (EXERGONIC!)
 Energetics of Cellular Metabolism
• Central principle of metabolism in living cells:

“Free energy released by exergonic reactions is

used by endergonic reactions.”
 ATP and Free Energy
• Some molecules like ATP (adenosine triphosphate)
contain high energy bonds such as phosphate bonds.
When these bonds break, energy is released.
 ATP and Free Energy
• Exergonic reaction
ATP  ADP + P + energy released
• Endergonic reaction
ADP + P + energy absorbed  ATP

Cells capture energy as chemical energy stored with

molecules of ATP. This captured energy is used to
drive energy-requiring reactions.
ATP is the central currency of energy in the cell.
 ATP and Free Energy
• Some pathways require inputs of ATP and use
the energy of ATP to drive endergonic
reactions.
• Living cells continuously form and consume
ATP.
 Redox Reactions
• Many metabolic reactions, including those
involved in energy capture and utilization
involve electron transfer.
Oxidation – loss of one or more electrons
Reduction – gain of one or more electrons
 Redox reactions
• Example:
Oxidation: 2(H2  2e- + 2H+)
H2 is electron donor (reducing agent).
Reduction: ½O2 + 2e-  O2-
O2 is electron acceptor (oxidizing agent)

Net reaction: H2 + ½O2  H2O

 Redox reactions
• Many enzymatic reactions require coenzymes
(small non-protein organic substances that
bind loosely to specific enzymes and assist in
their catalytic function).
• They can accept a chemical group (an
electron) produced by one enzymatic reaction,
hold on to it for a short time and then donate
it to the substrate of another reaction.
 Redox reactions
• Oxidation of a substrate is often coupled to the
simultaneous reduction of a coenzyme.
Example coenzyme: nicotinamide adenine dinucleotide
(NADH)
Redox Reactions
 Redox Reactions
• Molecules vary with regard to how easily they
gain or accept electrons. This ability is reflected
in the value of their reduction potential.
• The reduction potential of a substance is a
value indicating how readily a substance
accepts/donates electrons. The susbstance
with the most positive reduction potential has
the greatest potential to accept electron (i.e.
the strongest oxidizing agent).
 Redox Reactions
• A redox reaction consists of an oxidation half reaction
and a reduction half reaction.
• Each half reaction has an electrical potential (E). By
convention, all half reactions are written as reductions
and the electrical potential for an oxidation half
reaction is equal in magnitude but opposite in sign to
the electrical potential for the corresponding
reduction.
• The electrical potential for a redox reaction is given by
E = Eox + Ered
 Redox Reactions
• The following table shows the reduction
potentials for the reduction of NAD+ and O2.

Reaction E

NAD+ + 2H+ + 2e-NADH + H+ -0.32

½ O2 + 2H+ + 2e-  H2O +0.82

 Redox reactions
• For the reduction of O2 coupled with the
oxidation of NADH, the potential for the
overall reaction is calculated as follows:
E (V)
Oxidation NADH+ + H+  NAD+ + 2H+ + 2e- 0.32
Reduction ½ O2 + 2H+ + 2e-  H2O 0.82
Net NADH + ½ O2 + H+  H2O + NAD+ 1.14
 Redox Reactions
• The electrical potential is related to the free energy (ΔG):
ΔG = -nFErxn
n- no. of electrons transferred (in moles, from the balanced
equation)
F – Faraday’s constant (96,485 C/mol)
ΔG is given in J, 1 J = 1V x 1C

The higher the electric potential of a reduction half

reaction; the greater the tendency for the species to
accept an electron.
 Redox reactions
• From the previous reaction
NADH + ½O2 + H+  H2O + NAD+ Erxn = 1.14 V
For the overall reaction involving the reduction
of 1 mole of O2 coupled with the oxidation of
NADH, the free energy change (ΔG=-220 kJ) is
negative. Hence, the reaction is spontaneous.
Redox Reactions
Redox Reactions
Redox Reactions
 Metabolic Strategies for Generating ATP

• ATP synthesis
- through metabolism of inorganic substrates
- through conversion of light energy 
chemical energy
- utilization of organic substrates
Two different mechanisms for generating ATP
- Substrate-level phosphorylation
- Chemiosmosis
 Metabolic Strategies for Generating ATP

• Substrate-level phosphorylation
Free energy released from exergonic reaction supplies the
free energy required to combine inorganic phosphate or
(Pi) or phosphate from an organic molecule and ADP to
form ATP
Example:
Net: Phosphoenolpyruvate + ADP  pyruvate + ATP

Phosphoenolpyruvate  pyruvate (exergonic)

ADP  ATP (endergonic)
 Metabolic Strategies for Generating ATP

• Chemiosmosis
ATP  ATP (endergonic)
Movement of protons down a proton gradient
across a membrane (exergonic)
 Autotrophic and Heterotrophic Metabolism

• Autotrophic
- self-feeding
- uses inorganic carbon (CO2) as carbon source
• Heterotrophic
- requires supply of preformed organic matter for the
production of cellular biomass as a source of chemical
energy used to form ATP
- Involves conversion of the organic substrate molecule to
end products via a metabolic pathway that releases
sufficient energy for it to be coupled to the formation of ATP
Autotrophic and Heterotrophic Metabolism
 Heterotrophic metabolism
• Two basic types of heterotrophic metabolism
- Respiration
- Fermentation
 Heterotrophic metabolism
• Respiration
- Requires an external electron acceptor not
derived from the organic substrate
- Reduction of final electron acceptor balances
the oxidation of initial substrate i.e. the
electron donor
 Heterotrophic metabolism
• Fermentation
Fermentation is metabolism in which energy is
derived from the partial oxidation of an organic
compound using organic intermediates as
electron donors and acceptors.
No outside electron acceptors are involved; no
membrane or electron transport system is
required; all ATP is produced by substrate-level
phosphorylation.
 Respiratory Metabolism
• Aerobic metabolism begins with an organic
molecule combines with oxygen in a redox
process which ends to the formation of CO2
and H2O plus a substantial amount.

Example: Aerobic respiration of glucose

C6H12O6 + 6O2  6CO2 + 6H2O (+ 38 ATP
produced/mol glucose)
 3 Phases of Respiratory Metabolism
(1) A pathway during which the organic molecule is broken down
into smaller molecules usually with the generation of some ATP
and reduced coenzymes.
(2) The tricarboxylic acid cycle (TCA), during which the small
organic molecules produced in the first phase are oxidized to
inorganic carbon dioxide and water, accompanied with
production of more ATP and reduced coenzymes.
(3) Oxidative phosphorylation, during which
- Reduced enzymes are reoxidized
- Electrons released are transported through a series of
membran-bound carriers to establish a proton gradient across a
membrane
- A terminal acceptor such as O2 is reduced and ATP is synthesized
3 Phases of Respiratory Metabolism
Glycolysis
 Glycolysis
• Breaks down glucose to a 3-C sugar, pyruvate
• Net rxn: Glucose + 2Pi + 2NAD+ + 2ADP  2
pyruvate + 2NADH + 2ATP
Glycolysis
Tricarboxylic acid (TCA) or Krebs cycle
Tricarboxylic acid (TCA) cycle or Krebs cycle

• Net reaction: 2 pyruvate + 2ADP + 2FAD +

8NAD+  6CO2 + 2ATP + 2FADH2 + 8NADH
Tricarboxylic acid (TCA) cycle or Krebs cycle

• At the end of the TCA, all the carbon has been

converted to CO2.
• TCA is central to the flow of carbon through
the cell.
• It supplies organic precursor molecules to
many biosynthetic pathways.
Oxidative Phosphorylation: Electron
Transport Chain
 Oxidative Phosphorylation – Electron
Transport Chain
• During oxidative phosphorylation,
electrons from the reduced coenzymes
NADH and FADH2 are transferred through
a series of membrane-bound carriers that
form an electron transport chain.
• The electron transport chain involves
sequential transfer of electrons from
carriers with low reduction potentials to
carriers with higher reduction potential.
Eventually, a terminal electron acceptor
is reduced.
 Oxidative Phosphorylation – The Electron
Transport Chain
• The transfer of electrons through the
electron transport chain is spontaneous!
 Oxidative Phosphorylation – Electron
Transport Chain

• The electron transport

chain generates a proton
(H+) gradient across the
cytoplasmic membrane
(or inner mitochondrial
membrane in eukaryotic
cells) via a proton pump.
Oxidative phosphorylation – Chemiosmosis

• The proton gradient drives the diffusion of H+

back to the matrix inside the inner
mitochondrial/cytoplasmic membrane. When
H+ spontaneously diffuses back across the
membrane, ATP is synthesized.
• ATP synthase catalyzes the formation of ATP
using the proton gradient.
Oxidative phosphorylation
Aerobic Respiration: summary
Net ATP Generation
 Anaerobic Respiration
• The final electron acceptors in anaerobic respiration
include NO3-, SO42-, and CO32-.
Terminal reduction process in electron transport chain:
NO3-  NO2-
SO42-  H2S
CO32-  CH4
* The total ATP yield is less than in aerobic respiration
because only part of the Krebs cycle operate under
anaerobic conditions.
Anaerobic Respiration
 Fermentaion
• Fermentation is any process that releases energy from
sugars or other organic molecules by oxidation. It does
not require oxygen, the Krebs cycle or an electron
transport chain. It uses an organic molecule as the
final electron acceptor.
• Fermentation can occur in the presence of O2.
• Fermentation produces two ATP molecules by
substrate-level phosphorylation.
• Electrons remove from the substrate reduce NAD+ to
NADH.
Fermentation
 Fermentation

The pyruvic acid produced from the partial oxidation of the substrate is
reduced. Part of the electrons lost during partial oxidation are gained
during the reduction of the partially oxidized intermediate.
 Fermentation
• In lactic acid fermentation, pyruvic acid is
reduced by NADH to lactic acid (by fermenters
such as Streptococcus and Lactobacillus).
• In alcohol fermentation, acetaldehyde is
reduced by NADH to produce ethanol (by
fermenters such as Saccharomyces and some
bacteria).
Fermentation
Fermentation
 Fermentation: Summary
• Uses terminal electron acceptor derived from
organic substrate. Both the electron donor
and electron acceptor are internal to the
organic substrate in a fermentation pathway.
• Can occur in the absence of air because there
is no requirement for O2 or an external
electron acceptor to achieve a balanced redox
reaction
 Fermentation: Summary
• Yields less ATP per substrate molecule than
respiration (because the organic susbtrate
molecule must serve as both the internal
electron donor and internal electron acceptor).
ATP generation is only during glycolysis.
• Not all C and H are oxidized to CO2 and H2O. C
and H are rearranged into a form containing
less chemical energy than that with which they
began.
Aerobic Respiration, Anaerobic Respiration,
and Fermentation
Metabolism: Catabolic and Anabolic
Pathways
Catabolism of Macromolecules
 Catabolism of lipids

• Lipase hydrolyze lipids into

glycerol and fatty acids
• Fatty acids are catabolized by
beta oxidation which produces
two carbon units linked to CoA
to make acetyl-CoA
• Catabolic products van be
further broken down in
glycolysis and Krebs cycle.
Catabolism of lipids
 Catabolism of proteins
• Hydrolysis of polypeptide chain
 Catabolism of proteins
• Transamination of proteins

• Before amino acids can be catabolized, they must be converted to various substances
that enter the Krebs cycle or glycolysis.
• Transamination (-NH2 transfer), decarboxylation (-COOH removal) and
dehydrogenation reactions convert amino acids to be catabolized into substances that
enter the glycolytic pathway or Krebs cycle
Biosynthesis: Anabolic pathways
Polysaccharide Biosynthesis
Lipid Biosynthesis
Amino Acid & Protein Biosynthesis
Purine & Pyrimidine Biosynthesis
Integration of Metabolism