Definition of Metabolism

Laws of Thermodynamics
Cellular Synthesis of ATP and the Electron
Transport System
Correlation: Inhibitors of Cellular Respiration
Bioenergetics
• The quantitative study of:
• The energy transformations in the living cell
• The nature and function of the chemical processes underlying these
transformations
Metabolism

• An intricate network of
multienzyme
reactions/processes highly
coordinated and regulated to
meet the needs of the cell
General Features of Metabolism

• Multi-step reaction pathway

AB CDE
• Enzyme-catalyzed steps
• Central reaction pathways/metabolites
• Few types of reactions
• Pathways are interrelated
• Regulatory mechanisms
Catabolism and Anabolism
• Catabolism- the breakdown of larger molecules into smaller ones;
an oxidative process that release energy

• Anabolism- the synthesis of larger molecules from smaller ones; a

reductive process that requires energy
Catabolism and Anabolism
• Catabolism-exergonic; converging
• Anabolism- endergonic;diverging
• Not enzymatically identical
• Both pathways occur in 3 major stages
• Both pathways are subject to regulation
Catabolism and Anabolism
Three Stages

1. the interconversion of polymers and complex lipids with monomeric

intermediates
2. the interconversion of monomeric sugars, amino acids, and lipids
with still simpler organic compounds
3. the ultimate degradation to , or synthesis from, inorganic
compounds, including CO2, H2O, and NH3
Strategy of Metabolism

• To provide ATP for the energy dependent activities of the cell

• To provide reducing power (NADH, NADPH, etc.)
• To provide building blocks
Why do we have to review
thermodynamics?
• Because living cells interconvert different forms of
energy and may exchange energy with their
surroundings
• Reactions of this type are governed by the laws of
thermodynamics
• Knowledge of these laws will facilitate a perception of
how energy-producing and energy-utilizing metabolic
reactions are permitted to occur within the same cell
and how an organism is able to accomplish various
work functions
Biological energy
transformations follow the
first and second laws of
thermodynamics
First Law of Thermodynamics

• States that energy can neither be created nor destroyed

• Stipulates that although energy may be converted from one form to
another, the total energy in a system must remain constant
First Law of Thermodynamics
• Energy can neither be created nor destroyed but can only be
transformed from one form to another
• H= Q - W
enthalpy heat absorbed work done
First Law of Thermodynamics
• Examples:
• Chemical energy from glucose converted to chemical energy, ATP
• In muscle, chemical energy from ATP may be converted to mechanical
energy during the process of muscle contraction
Second Law of Thermodynamics
• Entropy (S)- measure or indicator of the degree of disorder or
randomness in a system
• States that all processes, whether chemical or biological, tend to
progress toward a situation of maximum entropy
• Equilibrium- results when the randomness or disorder is at a
maximum
Second Law of Thermodynamics
• The Entropy of the universe increases during all chemical and
physical processes
• Q = T S
Heat temp entropy
Gibbs Free Energy Unifies the 1st and 2nd
Laws of Thermodynamics

• First Law: H = Q-W

• Second Law: Q= TS
• Combining the 2 equations:
H= T S –W
GIBBS FREE ENERGY:
G= -W; the capacity to do useful work
G= H - T S
Qualitative Evaluation of G

G predicts the direction of a reaction

• G<0: (-) exergonic; favorable
• G>0: (+) endergonic; not favorable
• G=0: at equilibrium

Unit of Energy: kcal; joules

G depends on the
concentration of reactants
and products
• In the reaction aAbB
• At constant temperature and pressure:

G = G0 + RTln [B]b

[A]a
Standard Free Energy Change, G0
• Equal to G under standard conditions, that is, when
reactants and products are kept at 1M concentrations
• ln of 1 = 0
G = G0 + 0
Relationship between G0 and Keq
• At equilibrium, G = 0
• Keq= [B]b/ [A]a
• 0= G0 + RTln [B]b
[A]a
G0= -RTlnKeq
Relationship between G0 and Keq
• The derived eqn allows some simple prediction

• If Keq= 1, then G0=0

• If Keq> 1, then G0<0
• If Keq< 1, then G0>0
G0 of two consecutive reactions are additive

• Ex.
Glucose + ATP  glucose 6-P + ADP G0=-4000cal/mol
glucose 6-P  fructose 6-P________G0=+400cal/mol
Glucose + ATP  fructose 6-P + ADP G0=-3600cal/mol
Adenosine Triphosphate
(ATP)
Adenosine Triphosphate (ATP)

• G0 of hydrolysis of ATP is approx. -7300 cal/mol for

each of the 2 terminal PO4 groups
• High-energy phosphate compounds
Very High Energy Phosphate Compounds

• Ex.
• PEP
• 1,3 bisphosphoglycerate
• Phosphocreatine
Have G0 of hydrolysis > -10,000cal/mol
Low Energy Phosphate Compounds
• Ex.
• Glucose 6-P
• Glycerol 3-P
• AMP
Have G0 of hydrolysis < -4000 cal/mol
Why not use very high- or
low- energy phosphate
compounds instead of ATP?
Electron Transport Chain
(ETC)
Where in the mitochondria is the Electron Transport
chain Located?
ETC
• Can also be called respiratory chain
• Present in the inner mitochondrial membrane
• Final common pathway by which electrons derived from different
fuels of the body flow to oxygen
Organization of ETC
• Can be divided into 5 separate enzyme complexes namely complex
I, II, III,IV, and V
• Complexes I-IV – contain part of the ETC
• Complex V - catalyzes ATP synthesis
Organization of ETC
• Each complex accepts or donates electrons to relatively mobile
electron carriers , such as coenzyme Q and cytochrome c
• Each carrier of the ETC can receive e- from an e- donor and can
subsequently donate e- to the next carrier in the chain, ultimately to
combine with oxygen and protons to form water
Reactions of the ETC
• 1. Formation of NADH
• 2. NADH dehydrogenase
• 3. Coenzyme Q
• 4. Cytochromes
• 5. Cytochrome a +a3
• 6. Inhibitors
Formation of NADH
• NAD+ is reduced to NADH by dehydrogenases (removes 2 H atoms
from their substrate)
• Both e- but only 1 H+ are transferred to the NAD+ forming NADH +
H+
NADH Dehydrogenase
• H+ + H- carried by the NADH are next transferred to NADH
dehydrogenase
• An enzyme complex embedded in the inner mitochondrial membrane
• This enzyme complex contains:
• FMN-accepts 2 H atoms, becoming FMNH2
• Several iron atoms paired with sulfur atoms - necessary for the transfer of H
atoms to coenzyme Q (ubiquinone)
Coenzyme Q
• Can accept H atoms both from FMNH2 (NADH dehydrogenase) and
FADH2 (succinate dehydrogenase and acyl CoA dehydrogenase)
Cytochromes
• e- are passed down the chain from coenzyme Q to cyt b, c, and
a+a3
• Contains a heme group made of a porphyrin ring containing an atom
of iron
• Cytochrome iron is reversibly converted from its ferric to its ferrous
form
Cyt a + a3
• Also called cytochrome oxidase
• At this site, the transported e- , molecular oxygen and free protons
are brought together to produce water
• Contains bound copper atoms required for complex reaction
Inhibitors of electron transport
• Prevent the passage of e- by binding to a component of the chain
• Ex.
• Amytal & rotenone- inhibits NADH dehydrogenase
• Antimycin – inhibits cyt b-c complex
• CN- and CO- inhibits cyt oxidase
Clinical Correlation
• Cyanide Poisoning- CN- acts as the final e- acceptor; mitochondrial
respiration and energy production cease; cell death occurs rapidly
• Hypoxic Injury- happens when a tissue is deprived of its oxygen
supply as a result of e- transport inhibition; dec ATP; inc anaerobic
glycolysis; inc lactic acid; dec pH; damage lysosomal membranes;
digestion of cellular components
Standard Reduction Potential (E0)
• Characterizes the tendency of a redox pair to lose e-
• The more negative the E0 of a redox pair, the greater the tendency
of the reductant member of that pair to lose e-
• Ex.
NAD+ + 2H+ + 2e-  NADH + H+ E0=-0.32
1/2Oxygen +2 H+ +2e-  H2O E0= +0.82
Oxidative Phosphorylation:
Chemiosmotic Hypothesis
• Also known as the Mitchell Hypothesis
• Explains how the free energy generated by the transport of e- via
ETC is used to produce ATP from ADP and Pi.
Oxidative Phosphorylation:
Chemiosmotic Hypothesis
• Electron transport is coupled to transport of protons across the inner
mitochondrial membrane from the matrix to the intermembrane
space
• Creates an electrical gradient and pH gradient which produces
energy sufficient to drive ATP synthesis
Oxidative Phosphorylation:
Chemiosmotic Hypothesis
• The enzyme complex ATP synthetase (complex V) synthesizes ATP
using the energy of the proton gradient generated by ETC; converts
ADP and Pi to ATP and H2O
Oxidative Phosphorylation:
Chemiosmotic Hypothesis
• The chemiosmotic hypothesis proposes that after protons have been
transferred to the cytosolic side of the inner mitochondrial
membrane, they can reenter the matrix by passing through a
channel in the ATP synthetase molecule resulting in the synthesis of
ATP from ADP and Pi and at the same time, dissipating the pH and
electrical gradients
• Assignment :
• Research on the Inhibitors of Oxidative Phosphorylation