Chapter 11, 12, 13: Bioenergetics

Importance

• Bioenergetics is the study of energy changes accompanying biochemical reactions (metabolism)

• Malnutrition is associated with energy imbalance
o Undernutrition is low energy consumption (leads to marasmus or kwashiorkor in children)
o Overnutrition is excess storage of surplus energy (obesity)
• Death from starvation (no energy consumption) occurs when available energy body reserves are depleted

Energy Generation

• How we measure energy available to the system for doing work is called:
o Gibbs change in free energy (G)
o Two types of chemical reactions involve changes in energy
• Exergonic reactions – a reaction that proceeds spontaneously with the loss of free energy (-G)
• Endergonic reactions – a reaction that proceeds only if free energy is available to be gained (+G)
o

• Coupled reactions – reactions that gain energy by chemical linkage to oxidative reactions that loss energy
o The conversion of A → B occurs spontaneously with release of free energy (-G) (exergonic)
o It is coupled to another reaction in which free energy is gained for the conversion of C → D (+G)
(endergonic).
o Some free energy released from exergonic reactions will always remain (surplus) and will be lost as heat

Energy Involving Pathways

Metabolism – chemical processes that occur within a living organism to maintain life

• Catabolism – breakdown or oxidation of fuel molecules from food accompanied with the release of free energy
• Anabolism – synthesis reactions that build substances with the gaining of free energy
 o In humans, high energy intermediates are used to store free energy between these processes

Energy Containing Intermediates

High energy intermediates:

• Creatine phosphate (stored in skeletal muscles and brain)

o Maintains ATP levels in actively contracting muscles for a short period of time
• ATP – adenosine triphosphate (2 high energy phosphate bonds)
o Classified as a nucleotide
o Stored in very small amounts in most cells
o Produced during catabolism

Sources of Free Energy

• Catabolic pathways = pathways where ATP or creatine phosphate are produced

o Oxidative phosphorylation (respiratory chain)
o Glycolysis
o Citric Acid Cycle
o Phosphagens (creatine phosphate)

Use of Free Energy

• Anabolic pathways = pathways that utilize ATP as a substrate to produce larger molecules
o Gluconeogenesis
o Glycogenesis
o Fatty acid and triacylglycerol (fat) synthesis
o Protein synthesis
ATP-Driven Reactions

• Allows thermodynamically unfavorable reactions (endergonic) to occur

• Example:
o (1) Glucose + Pi → Glucose 6-phosphate + H2O (endogenic)
▪ (G = +13.8 kJ/mol) (endergonic: needs energy to proceed)
o (2) ATP → ADP + Pi (exergonic = release of energy)
▪ (G = -30.5 kJ/mol)

Energy Generation

• Coupled Together:
• Glucose + ATP → Glucose 6-phosphate + ADP
13.8 + (-30.5)
G = -16.7 kJ/mol (heat production)
• Thus, the phosphorylation of glucose occurs irreversibly due to the differing energy values

Biological Oxidation

• Humans are dependent on a supply of oxygen by respiration (aerobic) to produce sufficient amounts of energy
to survive
o Formation of ATP by which hydrogen reacts with oxygen to form water (respiratory chain)
• Oxidation = gain of O2 or loss of H atoms or loss of electrons
• Reduction = gain of H atoms or gain of electrons, or loss of O2
o Oxidation does not always require O2

Oxidoreductases

• (1) Oxidases – catalyze the removal of hydrogen atoms from one substrate using O2 (as the other substrate) as a
hydrogen acceptor
o Forms H2O or H2O2
o Contain either Fe or Cu as cofactors
o A major coenzyme used are flavoproteins
▪ Contain flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) made from riboflavin
(vitamin B2) and produce FADH2 or FMNH2 (reduced coenzymes)
▪ FAD → FADH2; FMN → FMNH2
• (2) Dehydrogenases – transfer of hydrogen atoms from one substrate to another substrate (not O2) or act as
components in the respiratory chain
o A major coenzyme used is nicotinamide adenine dinucleotide (NAD+) or nicotinamide adenine
dinucleotide phosphate (NADP+) made from niacin (vitamin B3) to produce NADH or NADPH (reduced
coenzymes). NAD+ → NADH; NADP+ → NADPH
 o Some use FAD and FMN as well
• (3) Hydroperoxidases – use hydrogen peroxide or an organic peroxide as a substrate
o Catalase: 2H2O2 → 2H2O + O2
o Peroxidases: destruction of peroxides through the conversion of reduced glutathione to oxidized
glutathione
▪ H2O2 + AH2 → 2H2O + A
• (4) Oxygenases – catalyze the incorporation of O2 (either both atoms or one) into a substrate molecule
o Mixed function oxidases (monooxygenases)
▪ AH + O2 + ZH2 → AOH + H2O + Z
o Cytochromes P450 enzymes (heme-containing monooxygenases) for detoxifying and metabolism of
drugs and hydroxylation of steroids
o Superoxide dismutase (prevents oxygen toxicity due to superoxide free radical formation)

Respiratory Chain (ETC: electron transport chain)

• Reduced coenzymes (FADH2 and NADH) from biological oxidations deliver H+ (protons) and electrons to
respiratory chain
o These particles are passed through various process to their final reaction with oxygen to form water
• Mitochondria:
o Outer membrane is semipermeable
o Intermembrane space
o Inner membrane is selectively permeable
▪ Transport proteins, respiratory chain enzymes, ATP synthase, cardiolipin (phospholipid)
o Matrix (inner most)
▪ DNA
Oxidative Phosphorylation (Chemiosmotic Theory)

• As electrons pass down from one complex to the next, H+ (protons) are ejected from the matrix to the
intermembrane space at certain complexes (proteins) (Fig 13-7)
o Complexes I, III, and IV act as proton pumps
• The inner membrane is impermeable to ions, so the H+ accumulate in the intermembrane space.

• This sets up an electrochemical potential; get an uneven distribution between H + outside (intermembrane
space) (positive) vs inside (matrix) (negative)
o Intermembrane space is more acidic, matrix more alkaline

• H+ gain entrance back through inner membrane (inside to matrix) thru a “proton channel”
o F0 – F1 dimer
• As H+ pass thru the F0 subunit, it activates the F1 subunit: which contains the enzyme ATP synthase, which
catalyzes ADP + Pi → ATP

• One mitochondrial NADH produces 2.5 ATPs in the respiratory chain

• One mitochondrial FADH2 produces 1.5 ATPs in the respiratory chain
• One cytosolic NADH produces either 2.5 or 1.5 ATPs in the respiratory chain dependent upon tissue (and
mitochondrial protein shuttles to move it from cytosol to mitochondria)

Mitochondrial Protein Shuttles

• Since the inner membrane is impermeable to most things, many protein shuttles / transporters exist
• Pyruvate utilizes a symport transporter with the help of protons to cross the inner membrane
• Citrate uses a transporter with malate
 • Fatty acids utilize carnitine for transport

• Glycerophosphate shuttle is used in all tissues, except heart

o In cytosol: NADH + H+ + DHAP → NAD+ + glycerol 3-phosphate
▪ Glycerol 3-phosphate crosses mitochondrial outer membrane into the intermembrane space:
o Where: Glycerol 3-phosphate + FAD → DHAP + FADH2
o FADH2 passes through inner membrane then goes to complex II of respiratory chain to produce 1.5 ATPs

• In the heart, we use the malate shuttle

o In cytosol: NADH + H+ + oxaloacetate → NAD+ + malate
▪ malate crosses mitochondrial outer and inner membrane with -ketoglutarate being sent out
o In mitochondria matrix: malate + NAD+ → oxaloacetate + NADH + H+
▪ NADH goes to respiratory chain to produce 2.5 ATPs
o Thus, cytosolic NADH produced in heart tissue provides more ATPs than cytosolic NADH produced in
skeletal muscle or brain

Respiratory Chain Control

• Availability of ADP (usually produced from the use ATP)

• Availability of NADH and FADH2 (produced from many pathways)
• Availability of O2
o Allows the capture of energy from food in a stepwise, efficient, and controlled (biological) rather than
explosive, inefficient, and uncontrolled (non-biological) manner

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