Biochemistry

College of Life Sciences

Zhejiang University
Wei-Jun Yang Ph.D.
w_jyang@cls.zju.edu.cn
0571-88273176
ftp://marine:marine@10.71.111.24/
I Introduction
II Foundations of Biochemistry
III Structure and Catalysis and
Information Pathways
V Bioenergetics and Metabolism
 III Bioenergetics and Metabolism
13 Principle of Bioenergetics
14 Glycolysis and the Catabolism
15 The Citric Acid Cycle
16 Oxidation of Fatty Acid
17 Amino Acid Oxidation and the Production of Urea
18 Oxidative Phosphorylation and Photophosphrylation
19 Carbohydrate Biosynthesis
20 Lipid Synthesis
21 Biosynthesis of Amino Acids, Nucleotides, and
Related Molecules
22 Integration and Hormonal Regulation of Mammalian
Metabolism
 Four Functions of Metabolism:
1. To obtain chemical energy by capturing solar energy
or by degradation of energy-rich nutrients from the
environment .
2. To convert nutrient molecules into the cell's own
characteristic molecules.
3. To polymerize monomeric precursors into
macrobiomolecules (proteins, nucleic acids, lipids,
polysaccharides).
4. To synthesize and degrade biomolecules required in
specialized cellular functions.
Photosynthesis Cellular respiration Biological work

Three Major Types of Energy Transformation

Biological Work Requires Energy
Hydrothermal vent（热液口）
 Two Groups of Metabolism
1. Autotrophs (自养生物，such as photosynthetic
bacteria and higher plants) can use carbon dioxide
from the atmosphere as their sole source of carbon,
from which they construct all their carbon-
containing biomolecules.
2. Heterotrophs（异养生物）cannot use atmospheric
carbon dioxide and must obtain carbon from their
environment in the form of relatively complex
organic molecules, such as glucose, proteins.
 Energy relationships between
catabolic and anabolic pathways
Catabolism（异化作用）:
The pathway degrade organic nutrients into
simple end products in order to extract chemical
energy and convert it into a form useful to the cell.
Anabolism（同化作用）:
The pathway start with small precursor molecules
and convert them to larger and more complex
molecules and require the input of energy.
 Energy relationships between
catabolic and anabolic pathways
Three types of molecular metabolic pathways
a; Converging catabolic b; Diverging anabolic
c; Cyclic pathway
14 Principle of Bioenergetics

*** Bioenergetics and Thermodynamics

*** Phosphoryl Group Transfers and ATP

*** Biological Oxidation-Reduction Reaction

Biological Energy Transformations Follow
the Laws of Thermodynamics

Two Laws of
Thermodynamics

The First Law;

The total energy in the
universe does not change
The second Law;
The entropy (disorder) of the universe
is increasing
Biological Energy Transformations
Follow the Laws of Thermodynamics
 Three thermodynamic quantities;
1. Gibbs free energy (G) and free-energy change, ΔG
2. Enthalpy (H) and Enthalpy change ΔH
3. Entropy (S) and Entropy change ΔS
Gibbs Free Energy (G);
expresses the amount of energy capable of doing work
during a reaction at constant temperature and pressure.
Free-energy Change (ΔG);
When ΔG°' is negative, the products contain less free
energy than the reactants. The reaction will therefore
proceed spontaneously to form the products under
standard conditions.
When ΔG°' is positive, the products of the reaction
contain more free energy than the reactants. The reaction
will therefore tend to go in the reverse direction if we start
with 1.0 M concentrations of all components.
The units of ΔG is joules/mole or calories/mole
Enthalpy (H，焓);
is the heat content of the reacting system. It reflects the
number and kinds of chemical bonds in the reactants
and products.

Enthalpy Change (ΔH);

When a chemical reaction releases heat, it is said to be
exothermic; the heat content of the products is less
than that of the reactants and ΔH has a negative value.
Reacting systems that take up heat from their
surroundings are endothermic and have positive values
of ΔH.
The units of ΔH is joules/mole or calories/mole
Entropy (S，熵);
is a quantitative expression for the randomness or
disorder in a system.

Entropy Change (ΔS);

When the products of a reaction are less complex and
more disordered than the reactants, the reaction is said
to proceed with a gain in entropy (p. 72).
The units ΔS is joules/mole•degree Kelvin.
 In Biological Systems
(at constant temperature and pressure)
ΔG = ΔH - TΔS
T is the absolute temperature.
When entropy increases, ΔS has a positive sign. When
heat is released by the system to its surroundings, ΔH
has a negative sign. Either of these conditions, which
are typical of favorable processes, will tend to make
ΔG negative. In fact, ΔG of a spontaneously reacting
system is always negative.
Actual Free energy Changes Depend on the
Concentration of Reactants and Products
ΔG°' = -RT ln K'eq
14 Principle of Bioenergetics
*** Bioenergetics and Thermodynamics

*** Phosphoryl Group Transfers and ATP

*** Biological Oxidation-Reduction Reaction

ATP: Adenosin triphosphate
ADP: Adenosin diphosphate
AMP: Adenosin monophosphate
Major Function of ATP in Cells
Heterotrophic cells obtain free energy in a chemical
form by the catabolism of nutrient molecules and use
that energy to make ATP from ADP and Pi. ATP then
donates some of its chemical energy to endergonic
processes such as the synthesis of metabolic
intermediates and macromolecules from smaller
precursors, transport of substances across membranes
against concentration gradients, and mechanical
motion.
The Free-Energy Change for ATP
Hydrolysis Is Large and Negative
Although its hydrolysis is highly exergonic (ΔG°' = -
30.5 kJ/mol), ATP is kinetically stable toward
nonenzymatic breakdown at pH 7 because the
activation energy for ATP hydrolysis is relatively high.
Rapid cleavage of the phosphoric acid anhydride bonds
occurs only when catalyzed by an enzyme.
The actual free energy of hydrolysis (ΔG) of ATP in living cells
is very different (not 30.5 kJ/mol).
Furthermore, the cytosol contains Mg2+, which binds to ATP
and ADP. In most enzymatic reactions that involve ATP as
phosphoryl donor, the true substrate is MgATP2- and the
relevant ΔG°' is that for MgATP2- hydrolysis.

ΔG for ATP hydrolysis in

intact cells, usually
designated ΔGP, is much
more negative than ΔG°'
in most cells ΔGP ranges
from -50 to -65 kJ/mol.
Other Phosphorylated Compounds and
Thioesters Also Have Large Free
Energies of Hydrolysis

1. Phosphoenolpyruvate（磷酸烯醇式丙酮酸）
2. 1,3-bisphosphoglycerate（甘油-1,3-二磷酸）
3. Phosphocreatine（磷酸肌酸）
4. Thioesters（硫酯）
Other Phosphorylated Compounds and
Thioesters Also Have Large Free
Energies of Hydrolysis
Phosphoenolpyruvate
（磷酸烯醇式丙酮酸）
1,3-bisphosphoglycerate
（甘油-1,3-二磷酸）
Phosphocreatine（磷酸肌酸）
Thioesters（硫酯）
ATP Provides Energy by Group Transfers, Not by
Simple Hydrolysis
Two groups of phosphate compounds in living organisms.
High-energy compounds; ΔG°' ＜ -25 kJ/mol
"low-energy" compounds; ΔG°' ＞ -25 kJ/mol

Flow of Phosphoryl Groups

14 Principle of Bioenergetics
*** Bioenergetics and Thermodynamics

*** Phosphoryl Group Transfers and ATP

*** Biological Oxidation-Reduction Reaction

The transfer of phosphate groups is one of the central
features of metabolism. Metabolic electron transfer
reactions are also of crucial importance.
The path of electron flow in metabolism is complex.
Electrons move from various metabolic intermediates
to specialized electron carriers in enzyme-catalyzed
reactions. Those carriers in turn donate electrons to
acceptors with higher electron affinities, with the
release of energy. Cells contain a variety of molecular
energy transducers, which convert the energy of
electron flow into useful work.
The Flow of Electrons Can Do Biological Work
The energy made available to do work by this
spontaneous electron flow (the free-energy change
for the oxidation-reduction reaction) is proportional
to ΔE:

ΔG=-nFΔE, or ΔG°'=-nFΔE'0
Acetaldehyde（乙醛）is reduced by NADH:
Acetaldehyde + NADH + H+ ethanol + NAD+

The relevant half reactions and their Eo values are:

(1) Acetaldehyde + 2H+ + 2e- ethanol E'0 = -0.197 V
(2) NAD+ + 2H+ + 2e- NADH + H+ E'0 = -0.320 V

ΔE0 = -0.197 V - (-0.320 V) = 0.123 V, and n is 2.

ΔG°' = -nFΔE'0 = -2(96.5 kJ/V•mol)(0.123 V) = -23.7
kJ/mol.
 Soluble Electron Carriers
1. Nicotinamide adenine dinucleotide (NAD+，
烟酰胺腺嘌呤二核苷酸)

2. Nicotinamide adenine dinucleotide

phosphate (NADP+，磷酸烟酰胺腺嘌呤二核苷酸)
3. Flavin mononucleotide (FMN，黄素单核苷酸)
4. Flavin adenine dinucleotide (FAD，黄素腺嘌呤
二核苷酸)
NADH and NADPH Act with Dehydrogenases
（脱氢酶）as Soluble Electron Carriers
Flavoproteins Contain Flavin（黄素）Nucleotides
 Topics for Next Chapter
1. Glycolysis: two phases and ten steps of glycolysis
（第6组）
2. Three fates of pyruvate under aerobic and
anaerobic conditions（第7组）
3. Microbial fermentations yield alcohol and other
end products of commercial value （第8组）
4. Feeder pathways for glycolysis（第9组）
5. Regulation of carbohydrate catabolism（第10组）
6. The pentose phosphate pathway of glucose
oxidation（第11组）