CHAPTER VII

Bioenergetics

LEARNING OBJECTIVES:

At the end of this chapter, the students are expected to:

1. Recall the basic concepts of thermodynamics
2. Understand how the body makes use of energy in the form of ATP

BIOENERGETICS
• The study of the transfer and utilization of energy in biologic systems

CHANGE IN ENTHALPY (ΔH)

• Measure of change in heat content of the reactants and
products
• Measured in joules (J)
• Exothermic process releases heat, causing the temperature
of the immediate surroundings to rise. E.g. the substrate has
high heat content and the product is low.
• Endothermic process absorbs heat and cools the
surroundings. E.g. the substrate has low heat content and the
product is high.

CHANGE IN ENTROPY (ΔS)

• Measure of the change in randomness or disorder of the reactants and products in a system. E.g. Ice in a room
temperature
• Measured in joules/Kelvin (J/K)

CHANGE IN FREE ENERGY (ΔG)

• Energy available to do work
ΔG = ΔH - T ΔS
Where T = absolute temperature in Kelvin
• Predicts the direction in which a reaction will spontaneously proceed
• Predicts whether a reaction is favorable (-G gives spontaneous and favorable reaction)
• Approaches zero as reaction proceeds to equilibrium

Standard Free Energy Change (ΔGO)

• ΔGO = - RT ln Keq
• ΔG under standard conditions
• [Reactants] and [Products] are 1 molar each
• Temperature is 25°C or 298 K
• Pressure is 1 atmosphere
COUPLING REACTIONS
• ΔGO of two consecutive reactions are additive
• All ΔGs of a pathway are additive
o A large negative ΔG reaction will couple with a smaller positive
ΔG reaction to yield an overall negative reaction
o Endergonic processes proceed by coupling to exergonic
processes

ADENOSINE TRIPHOSPHATE (ATP)

• Adenosine molecule to which three phosphate groups
are attached
• Acts as the energy currency of the cell, transferring free
energy derived from substances of higher energy
potential to those of lower energy potential
• Hydrolysis of ATP yields a large – ΔGO
• ATP → ADP + Pi (ΔGO = –7300 cal/mol)

HOW IS ATP PRODUCED?

1. SUBSTRATE LEVEL PHOSPHORYLATION
• Done through coupling reactions where a phosphate group is
transferred to ADP from another substance with higher ΔG O
Glycolysis - Net formation of two high energy
phosphates results from thE formation of lactate from one
molecule of glucose, generated in two reactions catalyzed by phosphoglycerate kinase and pyruvate
kinase
Citric acid cycle - One high energy phosphate is generated directly at the succinyl thiokinase step
 2. OXIDATIVE PHOSPHORYLATION
• Greatest quantitative source of high energy
phosphate in aerobic organisms
• Free energy comes from successive oxidation
of substances in the respiratory chain within
mitochondria
• Molecular O2 is the final substance to be
reduced

ELECTRON TRANSPORT CHAIN (ETC)

• Final common pathway by which electrons from the
different fuels of the body flow to oxygen
• Located in the mitochondria, specifically, in the
inner membrane
• 2 electron carriers used in the ETC:
o Nicotinamide Adenine Dinucleotide (NAD+)
o Flavin Adenine Dinucleotide (FAD) • NAD+ and
FAD receive electrons (i.e., they undergo
REDUCTION) from other substances to form NADH
and FADH2
• NADH and FADH2 each donate electrons to a specialized set of electron carriers in the inner
mitochondrial membrane
Mechanism:
• All components are fixed to the inner mitochondrial membrane
except coenzyme Q and cytochrome C
• Ubiquinone (CoQ) is the only non-protein component of the ETC
• Protons (H+) are pumped to the intermembranous space in 3
complexes (I, III, and IV)
• This creates an electrical gradient across the inner mitochondrial
membrane
• Final electron acceptor is oxygen (O2)
Mitchell Hypothesis
The chemiosmotic hypothesis explains how the free energy generated by the transport of electrons by the
electron transport chain is used to produce ATP from ADP + Pi.

CLINICAL CORRELATES
• When there is lack of O2, there is decreased activity of the electron transport chain
• ATP production shifts from oxidative phosphorylation to substrate-level phosphorylation
o Substrate-level phosphorylation does not require oxygen, but anaerobic glycolysis is not enough for
highly aerobic tissues like neurons and cardiac muscle

ETC INHIBITORS
• Compounds that prevent the passage of electrons by binding to
a component of the ETC, blocking the redox reactions
• Effects
o ↓ oxygen consumption
o ↑ intracellular NADH/NAD+ and FADH2/FAD ratios
NADH and FADH2 accumulate because they cannot transfer
electrons to the ETC
o ↓ ATP

UNCOUPLERS
• Compounds that increase the permeability of the inner mitochondrial membrane to protons
• Electron transport proceeds at a rapid rate without establishing a proton gradient
• Effects:
o ↑ oxygen consumption
o ↓ NADH/NAD+ and FADH2/FADH ratio
o ↓ ATP synthesis
• Examples:
o Synthetic: 2,4 dinitrophenol, aspirin (hyperpyrexia)
o Uncoupling protein: Thermogenin (brown fat)
o Malignant Hyperthermia (↑ TCA)

REACTIVE OXYGEN SPECIES

• Unstable products that are formed as a byproduct of the ETC, when
molecular oxygen (O2) is partially reduced:
o superoxide (∙O2-)
o hydrogen peroxide (H2O2)
o hydroxyl radical (OH∙)
• Produced by neutrophils to kill bacteria
• Increased during reperfusion injury
o React with lipids to cause peroxidation to cause disruption of cell
membranes
o Denatures and precipitates proteins and other substrates
• Defenses against ROS accumulation:
MITOCHONDRIAL DISEASES
• Mutations in mitochondrial DNA affect tissues with the greatest ATP requirement
• Follow non-Mendelian genetics
• Examples:
o Fatal infantile mitochondrial myopathy and renal dysfunction

o Mitochondrial Encephalomyelopathy, Lactic Acidosis, and Stroke-like episodes (MELAS)

• encephalomyopathy clinically characterized by short stature, stroke-like episodes, migrainous
headaches, vomiting, seizures, and lactic acidosis
• between age 5 and 15 years

Leber Hereditary Optic Neuropathy (LHON)

• point mutations in mitochondrial DNA result to loss of retinal ganglion cell, leading to late onset acute
optic neuropathy and bilateral central vision loss
• majority from mutation in NADH dehydrogenase