BIOENERGETICS AND

OXYGEN TOXICITY

Rondang R. Soegianto
2009
1

I. Bioenergetics
Terminology:

Bioenergetics
Energy trransduction
Biochemical thermodynamics

Central theme: Understanding the mechanism

of ATP synthesis through
the oxidation of substrates (Nicholls)
Specificity:

Describes the transfer and utilization

of energy in biologic
systems (Lippincott)

Gibbs free energy (G) and Gibbs change of free energy (G)

G = H - TS
T = absolute temperature
H = enthalpy, heat
S = degree of organization of atoms involved in
reaction
G = available useful energy

In the human body, T is constant

Thus:
H (enthalpy) changes are negligible and
principally associated with
chemical bonds known as Internal Energy
(Chemical Energy).
Meaning: H = G
Hence:
G = E - TS
(Lange, Exam. & Board Review)
Note:
Nonbiologic systems utilize heat energy
to
perform work. Biologic systems are isothermic and utilize

Sign of G predicts the direction of a reaction

G = negative: Reaction is exergonic
Proceeds with net loss of free energy
Reaction goes spontaneously
G = positive:

Reaction is endergonic
Proceeds only with net gain of energy

G = zero:

Sistem is at equilibrium
No net change takes place

Coupling of Endergonic to Exergonic Processes

Harper 21st, Fig. 11.1

Transfer of Energy via a High-energy Intermediate Compound

Harper 21st, Fig 11-3

Transduction
of energyof
through
........
Transduction
energy
thru common high-E comp.
Harper 21st, Fig 11-4

Harper 21st, Fig 11-4

Devlin 5th, p 538, Fig 13.1

High-energy phosphates are involved in coupling processes

Harper 26th, p 82

10

ATP = energy currency of the cell

Other nucleoside triphosphates: UTP,
GTP, CTP
May take part in phosphorylations in the
cell transferring free energy.

11

II.- Oxidation
Biologic
Oxidation
processes in living systems
- Catalyzed by class I enzymes:
Oxidoreductases

12

Definition:

Oxidation = Loss of electrons

Reduction = Gain of electrons

Oxidation-reduction (redox) reactions are reversible

A ox + B red
Fe2+

A red + B ox

Fe3+ + e13

Oxidoreductases

(Harper 26th)

1.

Oxidases:

A Containing Cu
B As flavoproteins

2.

Dehydrogenases:
A. NAD+ or NADP+ as coenzyme
B Flavin as coenzyme
C Cytochromes (Fe-porphyrin as coenzyme)

14

1.

Oxidases:
- Remove 2 protons (H+) from substrate and pass to oksigen
- Generate H2O or H2O2
Two groups of oxidases:
A Containing Cu
Example: Cytochrome a3 (cyt a3) also known as cyt aa3
Is a cytochrome oxidase
Terminal compound of the respiratory chain in
mitochondria
B. Flavoproteins, contain FMN or FAD
Ex. : L-aminoacid oxidase
Xanthine oxidase
Aldehyde dehydrogenase

15

2.

Dehydrogenases cannot use O2 as H or eacceptor

A. NAD+ or NADP+ as coenzyme
Generally:
NAD+-linked dehydrogenase in
energy transduction reaction
NADP+-linked (as NADPH)
dehydrogenase in reductive
synthesis

16

B. Flavin as coenzyme
Tightly bound to apoenzyme (prosthetic
Linked to e- transport of the respiratory

group)
chain

C. Cytochromes
Fe-containing hemoproteins
In the resp. chain: cyt b, c1, c, a (and cyt a3 which is
an oxidase)
Cyt also in endoplasmic reticulum (P450 and P5), in
plant cells, bacteria and yeast.

17

Peroxidase

3.

Hydroperoxidases use H2O2 as substrate

A. Peroxidase reduces peroxides using various eacceptors Gluthatione peroxidase
H2O2 + AH2

2 H 2O + A

In erythrocytes and other tissues:

H2O2 + 2 GSH

GSSG + H2O

GSH = Reduced gluthatione

Glutamyl-cysteinyl-glycine (a tripeptide)

18

B.

Catalase

Catalase
Hemoprotein with 4 heme groups
2 H2 O 2

2 H2 O + O 2

Found in: Blood, bone marrow, mucous

membranes
Kidney, liver
Catalase destroys peroxides formed by oxidases
19

4.

Oxygenases
Catalyze direct transfer & incorporation of oxygen into a
substrate molecule.
A. Dioxygenases
Incorporate both atoms of molecular oxygen into the
substrate.
A + O2 AO2
Example: Homogentisate dioxygenase (oxidase)

20

B.

Monooxygenases (Mixed-Function Oxidases, Hydroxylases)

Incorporate only one O atom into substrate.
The other O atom is reduced to water.
AH + O2 ZH2

AOH + H2O + Z

Examples: Detoxication of many drugs

Hydroxylation of steroids

21

Free radicals
- O
Transfer of a single e to
O - (superoxide anion)
2
2
Can damage membranes, DNA,
etc.

Destructive effects
Amplified by: Free radical chain reaction
Removed by: Superoxide dismutase (SOD) in the reactions
O

+ O -2H

SOD

H O

H O
2

Catalase
2

+ O
2

2H O + O
2

22

Mitochondria

Make > 90% of cellular ATP

Powerplant of the cell
Four Compartments
Matrix has numerous enzymes that reduce
NAD+ to NADH during catabolism of foodstuffs
Inner Membrane has:
Proteins

that transfer electrons (the ETS)

ATP synthase

Intermembrane Space
Outer Membrane
23

Faces of mitochondrial membrane

(V & V

Fig. 20-3)

24

Role of RC of mitochondria in the conversion of food energy to ATP

Harper 26
Fig. 12-2

25

Harper 26

Fig. 12-4

26

27

28

29

Cardiac muscle has high ATP demand.

Higher content of mitochondria than most
tissues.
High content of Electron Transport Chains
proteins: ATP synthase,
ATP-ADP translocase, TCA cycle.

30

Also:
High content of creatine kinase as energy
buffer and energy shuttle (as well as brain)
Heart (and brain) sensitive to ischemia and
anoxia decreased ATP production

31

Consequence of decreased ATP:

- Ion influx (Na+, Ca2+)
- Swelling of tissue
Cardiac mitochondria can sequester Ca 2+
Effect:
Low amt stimulates TCA
High amt activates phopholipase
degrades membrane lipids
32

33

34

35

36

37

38

39

40