Biochemistry II
--Metabolism,The degradation
and synthesis of biomolecules,
Chapter 19
An Overview of Metabolism
代谢的定义
? 生物代谢是指生物活体与外界环境不断进行的物
质（包括气体、液体和固体）交换过程。
? 合成代谢一般是指将简单的小分子物质转变成复
杂的大分子物质的过程。分解代谢则是将复杂的
大分子物质转变成小分子物质的过程。
? 糖、脂和蛋白质的合成代谢途径各不相同，但是
它们的分解代谢途径则有共同之处，即糖、脂和
蛋白质经过一系列分解反应后都生成了酮酸并进
入三羧酸循环，最后被氧化成 CO2和 H2O。
◆ ◆ 新陈代谢的类型,
新陈代谢
合成代谢
（同化作用）
分解代谢
（异化作用）
由小分子合成大分子
需要能量
将大分子分解成小分子
释放能量
1,The Roles of metabolism
Metabolism is a highly coordinated and directed cell activity,
in which many multienzyme systems cooperate to
accomplish four functions,
(l) to obtain chemical energy by capturing solar energy or by
degrading energy-rich nutrients from the environment;
(2) to convert nutrient molecules into the cell's own
characteristic molecules,including macromolecular
precursors;
(3) to polymerize monomeric precursors into proteins,
nucleic acids,lipids,polysaccharides,and other cell
components;
(4) to synthesize and degrade biomolecules required in
specialized cellular functions,
The energy supply
and demand in
Heterotrophs,
the ATP-ADP
cycle
2,The General Features of
metabolism
? Occurs in linear,branched or circular pathways;
? Highly interconnected (“Every road leads to
Rome”),
? Highly regulated to achieve the best economy
(“Balanced supply and demand”),
? The number of reactions is large (over 1000)
and the number of types of reactions is
relatively small.（ 见课本 p5~15）
? Well conserved during evolution,reflecting the
unity of the life phenomena (“what happens in
bacteria happens in human being”),
Degradation is convergent
and energy releasing
Synthesis is divergent
and energy consuming
The citric
acid cycle
乙酰辅酶 A
草酰乙酸 柠檬酸
异戊烯焦磷酸
3,Things that will be covered
? 1),General principles for bioenergetics,
2),Oxidative degradation of fuels (glycolysis,b-
oxidation,urea cycle,a-ketoacid oxidation,citric
acid cycle),generating NADH,FADH2,ATP,and
CO2,
3),Oxidation of NADH and FADH2 by O2 and
generation of ATP and H2O (respiratory chains,ATP
synthase),
4),Photosynthsis (photophosphorylation and carbon
fixation),
5),Regulation of metabolism,
4,Understanding
Metabolism,a retrospect
4.1 Sugar degradation
(glycolysis) and synthesis
? 1897,Eduard Buchner,Cell-free
fermentation (Nobel Prize in 1907),
? Otto Fritz Meyerhof,conversion of glucose
to lactic acid in muscle and back to
glucose in liver (Nobel Prize in 1922),
? Sir Arthur Harden and Hans von Euler-
Chelpin,involvement of enzymes,
coenzymes,and phosphorylated
intermediates (Nobel Prize in 1929),
? Carl Ferdinand Cori and Gerty Theresa
Cori,formation of glucose-1-phosphate
from glycogen and pyrophosphate by the
action of phosphorylase (Nobel Prize in
1947),
? Luis F,Leloir,UDP-glucose is the
precursor for glycogen synthesis (Nobel
Prize in 1970),
? The whole glycolysis pathway (conversion
of glucose to pyruvate) was revealed by
1940,
4.2 Complete oxidation of fuels,
from two-carbon units to CO2
? Albert von Szent-Gyorgyi,plant acids,fumaric
acid (反丁烯二酸 ),malic acid (苹果酸 ) were not
consumed,but act as catalysts for the cellular
combustion process (Nobel Prize in 1937),
? Fritz Albert Lipmann,role of co-enzyme A and
ATP (Nobel Prize in 1953);
? Sir Hans Adolf Krebs,Acetyl-CoA and citric acid
cycle (柠檬酸循环 ) for complete oxidation two-
carbon units (Nobel Prize in 1953),
4.3 Synthesis of ATP using energy
released from fuel oxidation
? Otto Heinrich Warburg,involvement of iron-
containing cytochromes (细胞色素 ) in cellular
respiration (Nobel Prize in 1931),
? Peter D,Mitchell,proposed the chemiosmotic
theory（ 化学渗透学说） to relate electron flow to
ATP synthesis in all organisms (Nobel Prize in
1978),
? Paul D,Boyer,John E,Walker,enzymatic
mechanism for ATP synthesis (Nobel Prize in
1997),
4.4 Lipid degradation and synthesis
? Konrad Bloch and Feodor Lynen,
pathways for cholesterol and fatty acid
synthesis (Nobel Prize in 1964),
? Michael S,Brown and Joseph L,Goldstein,
regulation of cholesterol biosynthesis
(Nobel Prize in 1985),
4.5 Regulation of Metabolism
? Earl W,Sutherland,Jr.,cAMP as the second
messager for hormones to regulate cell
metabolism (Nobel Prize in 1971),
? Alfred G,Gilman and Martin Rodbell,
involvement of membrane G-proteins in signal
transduction of hormones (Nobel Prize in 1994),
? Edmond H,Fischer and Edwin G,Krebs,
regulation of enzymatic activity by reversible
phosphorylation (Nobel Prize in 1992),
4.6 Photosynthesis
? Hans Fischer,constitution of chlorophyll
(叶绿素 ) and its similarity to heme (Nobel
Prize in 1930),
? Melvin Calvin,Calvin cycle for CO2
assimilation (Nobel Prize in 1961),
? Johann Deisenhofer,Robert Huber,and
Hartmut Michel,3-D structure of a
Photosynthetic reaction center from a
purple bacterium (Nobel Prize in 1988),
4.7 DNA,RNA and Protein synthesis
? Severo Ochoa and Arthur Kornberg,enzymatic
synthesis of RNA and DNA (Nobel Prize in
1959),
? Marshall W,Nirenberg,Har Gobind Khorana,
interpretation of the genetic codes in protein
synthesis (Noble Prize in 1968),
? Francois Jacob,Andre Lwoff,and Jacques
Monod,Mechanisms to switch genes one and
off in prokaryotes (Nobel Prize in 1965),
? David Baltimore,Renato Dulbecco,and Howard
Martin Temin,enzymatic RNA-dependent DNA
synthesis in tumor viruses (Nobel Prize in 1975),
? Barbara McClintock,mobile genetic elements or
transposons (Nobel Prize in 1983),
? Susumu Tonegawa,genetic principle for the
generation of antibody diversity (Nobel Prize in
1987),
? Sidney Altman and Thomas R,Cech,RNA
catalyzed RNA processing (Ribozyme,核酶 )
(Nobel Prize in 1989),
? Richard J,Roberts and Philip A,Sharp,
eukaryotic genes are split and have to be
spliced (剪接 ） after transcription (Noble Prize in
1993),
? Gunter Blobel,intrinsic signals govern protein
localization (Nobel Prize in 1999),
How to study Biochemistry II
? Compare and relate the chemical reactions (the
substrates,the products and the type of conversion)
enzymes,coenzymes,physiological roles,ways of
regulation involved,etc,(This must be similar/related
to that!)
? Understand the classical experiments and thoughts
that led to the revelation of the knowledge described
(why was one awarded the Nobel Prize?),
? Be aware with the degree of speculativeness on
certain models (nothing is 100% certain in science),
? Understand the aspects that need further studies (how
could I win a Nobel Prize?)
Chapter 20
Principles of
Bioenergetics
Bioenergetics (生物能学 ）
the quantitative study of energy
transductions in living cells and the chemical
nature underlying these processes,
一,Bioenergetics and
Thermodynamics
1,Cells need energy to do all
their work
? 形成和保持细胞高度有序的结构 (biosynthesis of
macromolecules),
? 推动所有类型的运动 (mechanical work and
transport),
? 建立跨膜的离子浓度和电荷梯度,
? 保持体温,
? 在某些生物中产生光,
? The,energy industry”(production,storage and
use) is central to the economy of the cell society!
2,Chemical energy is the favorable
energy form for cells to do all their work
? Antoine Lavoisier`s insight on animal respiration
in the 18th century,it is nothing but a slow
combustion of carbon and hydrogen (the same
nature as a lighting candle).(拉瓦锡 1743－ 1794)
? Living cells are generally held at constant
temperature and pressure,chemical energy
(free energy) has to be used by living organisms,
no thermal energy,neither mechanical energy is
available to do work in cells,
? Biological energy transformation obey the two
basic laws of thermodynamics revealed by
physicists and chemists in the 19th century,
energy can neither be created nor be destroyed
(but conserved); energy conversion is never
100% efficient (some will always be wasted in
increasing the disorder or,entropy” of the
universe),
? The free energy concept of thermodynamic is
more important to biochemists than to chemists
(who can always increase the temperature and
pressure to make a reaction to occur!),
3,The free energy (G) concept of
biochemical reactions
(1) Free energy (G),在恒定的温度和压力条件下，一个
生物化学反应或过程可以用来做功的能量的多少。注
意：自由能强调的是反应始态与终态之间的能量变化，
任何体系的绝对自由能是无法测定的。
(2) Free energy change (?G),即产物与反应物之间的
自由能差异。
(3) Gibbs 发现, 在恒定的温度和压力条件下，任何 自发
过程 的自由能都是减少的 (products should have
less free energy than reactants for a reaction to
occur spontaneously,i.e.,?G has a negative
value ).（ 注意,自发性与化学反应的速率没有任何
关系 ）
（ 4） 生物化学中的标准自由变化 (?G'o),value of the
change in free energy under conditions of 298 K
(25oC),1 atm pressure,pH 7.0 (chemists use pH
0,i.e.,the concentration of H+ they use is 1M,
not 10-7 M as biochemists use here) and initial
concentrations of 1 M for all reactants and
products (except H+),
（ 5） The actual free energy chang (?G )depends on
?G'o,temperature,ratio of product and reactant
concentrations (Q),
? ?G = ?G'o + RT ln Q
（ 6） Enzymes only speed up thermodynamically
favorable reactions (having a negative ?G) !
（ 7） ?Go'与 K ' eq 的关系 (the prime again
indicates its biochemical transformation),
at equilibrium,?G = 0,Q = K`eq,thus
? ?Go' = -RT ln K'eq
（ 8） 当两个反应偶联时,?G and ?G‘o 的值
具有加和性 （ additive ） (i.e.,sharing
common intermediates),因此，一个热力
学允许的反应可以驱动一个热力学不利的
反应, 这样的现象在生物化学中经常遇到。
Glucose + Phosphate → Glucose-6-phosphate + H2O
?Go? = +13.8 KJ/mol
ATP + H2O → ADP + Pi
?Go? = -30.5 KJ/mol
二,Phosphate Group
Transfers and ATP
1,ATP水解的标准自由能（ ?Go? ）,
[ATP] = [ADP] = [Pi] = 1mol/L,[H+] = 10-7 mol/L
?Go? = -30.5 KJ/mol
因此我们称 ATP为高能磷酸化合物,而发生断裂的
焦磷酸键称为高能键。 （注意：我们所说的高
能与化学中的高能键是完全不同的两个概念）
2,在细胞中,ATP水解的实际自由能变化（ ?G）
与 ?Go?差别很大,(?G'o is -30.5 kJ/mol; ?G in
cells is -50 to -65 kJ/mol)
? For example,in human erythrocytes the
concentrations of ATP,ADP,and Pi are
2.25,0.25,and 1.65 mM,respectively,the
pH is 7.0 and the temperature is 25° C,
ΔG =ΔG° '+ RT ln [ADP][P i] [ATP]
= -30,500 J/mol + (8.315 J/mol?K)(298 K)ln
[(2.50?10-4)(1.65?10-3)/(2.25?10-3)]
=-30,500 + 2,480ln(1.83?10-4)
=-51.8 (kJ/mol)
3,The ATP molecule is kinetically stable at
pH 7 (i.e.,it has a high activation energy,
?G? for hydrolysis) and enzyme catalysis is
needed for its hydrolysis,
4,ATP is not a long-term storage form of
free energy in living cells,being consumed
within a minute following its formation,A
resting human consumes about 40 kg of
ATP in 24 hours!
5,其他高能磷酸化物和硫酯类化合物,
6,ATP has an intermediate phosphoryl group
transfer potential,thus ADP can accept and
ATP can donate phosphoryl groups,
ATP provides energy by group transfer
(donating a Pi,PPi or AMP to form covalent
intermediates),not by simple hydrolysis,
ATP has an intermediate
phosphoryl group transfer
potential
ATP can transfer a Pi,PPi or AMP to a reactant
7,In the lab,as little as a few picomoles (10-12 mol) of
ATP can be measured using firefly luciferin and
luciferase (荧光素酶 ),using spectroscopic methods,
三,生物主要是通过氧化还原反应的电
子转移获得生物能
1,When electrons flow from a low affinity carrier
(reductant,e.g.,glucose) to a high affinity carrier
(oxidant,e.g.,O2),either in an electric battery or in
a living cell,energy is released and work can be
done,
? Oxidation of energy-rich biological fuels often
means dehydrogenation (catalyzed by
dehydrogenases,脱氢酶 ) from carbons having
various oxidation states,
? In the living cells,electrons are transferred directly
as electrons (between metal ions),as hydrogen
atoms (H++e-),or as a hydride ion (:H- or H++2e-),
生物细胞中氧化还原反应电子转移方式,
1,以电子的形式传递,
呼吸链中细胞色素之间的氧化还原反应。
2,以氢原子的形式传递,
以 FMN或 FAD为氢受体的脱氢反应。
3,以氢负离子（或 H+ + 2e-） 形式传递,
以 NADN+或 NADP+为受体的脱氢反应。
2,Reduction potentials (E) measure affinity for
electrons,
? The affinity for electrons of a compound (in its
oxidized form) is indicated by its reduction potential
(E),
? Standard reduction potential (Eo') of each oxidant
(a constant) is measured by connecting a half-cell
having the oxidized and reduced species of the
redox pair each at 1 M,or 1 atm for gases,pH 7 to
a reference half-cell having 1 M H+ and 1 atm H2,
whose Eo' is arbitrarily assigned as 0.00 V,
? A positive value of Eo' indicates a tendency to
acquire electron from the reference half cell (with
1M H+/1atm H2),
The standard reduction
potential (Eo') of a
conjugate redox pair
is measured by
connecting the sample
half-cell to the H+/H2
reference half-cell,
pH 7 pH 0
? Walther Nernst derived an equation that
relates standard reduction potential (E0) to
reduction potential (E) at any concentration
of oxidized and reduced species in the cell,
在生物化学中用 Eo'取代 Eo
Eo'
3,生物化学反应的自由能变化与电池电动势,
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 ΔGo'=-nFΔEo'
? Acetaldehyde + NADH + H+ → ethanol + NAD+
? The relevant half reactions and their Eo values are,
? (1) Acetaldehyde + 2H+ + 2e- → ethanol
Eo?= -0.197 V
? (2) NAD+ + 2H+ + 2e- → NADH + H+
Eo' = -0.320 V
? For the overall reaction,
ΔEo' = -0.197 V - (-0.320 V) = 0.123 V,
and n is 2,Therefore,
ΔGo' = -nFΔEo' = -2(96.5 kJ/V?mol)(0.123 V) = -23.7
kJ/mol,
5,A few universal carriers collect electrons from the
stepwise oxidation of various substrates,
? Cellular oxidation of a nutrient occurs via stepwise
reactions (pathways) for efficient energy
transduction,
? NAD+,NADP+,FAD,and FMN are universal
reversible electron carriers (as coenzymes of
various enzymes),
? NAD and NADP are dinucleotides able to
accept/donate a hydride ion (with 2e-) for each
round of reduction/oxidation,
? NAD (as NAD+) usually acts in oxidations and
NADP (as NADPH) in reductions,
? NAD and NADP can easily diffuse out of
the enzymes,but FMN and FAD are tightly
bound to the enzymes (thus being called
prosthetic groups,and the complex
proteins being called flavoproteins),
? NADH and FADH2 will be further oxidized
via the respiratory chain for ATP
production,
:H-
Quinonoid
NAD (Nicotinamide Adenine Dinucleotide) and
NADP (Nicotinamide Adenine Dinucleotide
Phosphate)
Nicotinamide
(derived from
niacin)
Benzenoid
(in solution)
Isoalloxazine
FMN (Flavin
mononucleotide) and
FAD (Flavin Adenine
Dinucleotide)
E o' of FAD/FMN often
differs in different flavoproteins,
which are often complex and
contain other inorganic ions to help
electron transfer
异咯嗪环
(derived from
riboflavin)
ATP的
水解和
镁离子
的作用
Carbons have
various
oxidation states,
with
hydrocarbon
being the most
reduced and
CO2 being the
most oxidizaed,
首先，在你们这个年龄应该充满理想和抱负，对知识、科学
和人生有着无限追求。所以，我觉得考研的主要目的是为了进
一步提高自己的知识层次，培养从事科学研究的能力，为实现
更大和更远的目标奠定基础。如果这样，你就应该选一个自己
喜欢的学科专业，立志为其不懈努力，奋斗不止。
其次，可能你对学科专业的认识还很模糊，难以确定自己
喜欢什么，并且近期目标就是考上研究生，那么，就根据自己
的专业知识能力和英语水平，选择比较有把握考上的单位。因
为三年以后如何变化和发展是很难预料的。也许，在这三年中，
你对科学的认识更加深刻，业务知识和科研能力都取得了飞跃
进展，到时考博和出国深造都有可能。往后的发展机遇可能更
多更好。
最后，如果你的目的就是为了研究生毕业后 容易 就业或找一
份好的工作，那么，我认为生物化学和分子生物学专业最
好。一是目前以及在未来一段时间内，这方面的专业人员
还比较短缺，例如，近年来，我们学院来了许多研究生和
博士生，但没有一个生物化学和分子生物学专业的，而我
们学院急需这方面的师资和学术骨干。并且据我了解，全
国普通高校都存在类似问题。二是随着生物技术的发展和
应用，我国生物技术产业将迅速发展，而生物化学和分子
生物学是生物技术的理论基础和技术支撑，所以未来的就
业机会很多。三是生物化学和分子生物学专业比较容易转
行，如你所说的健康和营养问题都离不开生物化学的理论
和技术。 既是 到一些公司搞营销，也属生物化学专业选择
面最广。
以上所述，仅是我个人的看法，还要根据你自己的情况
而定。
The End !
--Metabolism,The degradation
and synthesis of biomolecules,
Chapter 19
An Overview of Metabolism
代谢的定义
? 生物代谢是指生物活体与外界环境不断进行的物
质（包括气体、液体和固体）交换过程。
? 合成代谢一般是指将简单的小分子物质转变成复
杂的大分子物质的过程。分解代谢则是将复杂的
大分子物质转变成小分子物质的过程。
? 糖、脂和蛋白质的合成代谢途径各不相同，但是
它们的分解代谢途径则有共同之处，即糖、脂和
蛋白质经过一系列分解反应后都生成了酮酸并进
入三羧酸循环，最后被氧化成 CO2和 H2O。
◆ ◆ 新陈代谢的类型,
新陈代谢
合成代谢
（同化作用）
分解代谢
（异化作用）
由小分子合成大分子
需要能量
将大分子分解成小分子
释放能量
1,The Roles of metabolism
Metabolism is a highly coordinated and directed cell activity,
in which many multienzyme systems cooperate to
accomplish four functions,
(l) to obtain chemical energy by capturing solar energy or by
degrading energy-rich nutrients from the environment;
(2) to convert nutrient molecules into the cell's own
characteristic molecules,including macromolecular
precursors;
(3) to polymerize monomeric precursors into proteins,
nucleic acids,lipids,polysaccharides,and other cell
components;
(4) to synthesize and degrade biomolecules required in
specialized cellular functions,
The energy supply
and demand in
Heterotrophs,
the ATP-ADP
cycle
2,The General Features of
metabolism
? Occurs in linear,branched or circular pathways;
? Highly interconnected (“Every road leads to
Rome”),
? Highly regulated to achieve the best economy
(“Balanced supply and demand”),
? The number of reactions is large (over 1000)
and the number of types of reactions is
relatively small.（ 见课本 p5~15）
? Well conserved during evolution,reflecting the
unity of the life phenomena (“what happens in
bacteria happens in human being”),
Degradation is convergent
and energy releasing
Synthesis is divergent
and energy consuming
The citric
acid cycle
乙酰辅酶 A
草酰乙酸 柠檬酸
异戊烯焦磷酸
3,Things that will be covered
? 1),General principles for bioenergetics,
2),Oxidative degradation of fuels (glycolysis,b-
oxidation,urea cycle,a-ketoacid oxidation,citric
acid cycle),generating NADH,FADH2,ATP,and
CO2,
3),Oxidation of NADH and FADH2 by O2 and
generation of ATP and H2O (respiratory chains,ATP
synthase),
4),Photosynthsis (photophosphorylation and carbon
fixation),
5),Regulation of metabolism,
4,Understanding
Metabolism,a retrospect
4.1 Sugar degradation
(glycolysis) and synthesis
? 1897,Eduard Buchner,Cell-free
fermentation (Nobel Prize in 1907),
? Otto Fritz Meyerhof,conversion of glucose
to lactic acid in muscle and back to
glucose in liver (Nobel Prize in 1922),
? Sir Arthur Harden and Hans von Euler-
Chelpin,involvement of enzymes,
coenzymes,and phosphorylated
intermediates (Nobel Prize in 1929),
? Carl Ferdinand Cori and Gerty Theresa
Cori,formation of glucose-1-phosphate
from glycogen and pyrophosphate by the
action of phosphorylase (Nobel Prize in
1947),
? Luis F,Leloir,UDP-glucose is the
precursor for glycogen synthesis (Nobel
Prize in 1970),
? The whole glycolysis pathway (conversion
of glucose to pyruvate) was revealed by
1940,
4.2 Complete oxidation of fuels,
from two-carbon units to CO2
? Albert von Szent-Gyorgyi,plant acids,fumaric
acid (反丁烯二酸 ),malic acid (苹果酸 ) were not
consumed,but act as catalysts for the cellular
combustion process (Nobel Prize in 1937),
? Fritz Albert Lipmann,role of co-enzyme A and
ATP (Nobel Prize in 1953);
? Sir Hans Adolf Krebs,Acetyl-CoA and citric acid
cycle (柠檬酸循环 ) for complete oxidation two-
carbon units (Nobel Prize in 1953),
4.3 Synthesis of ATP using energy
released from fuel oxidation
? Otto Heinrich Warburg,involvement of iron-
containing cytochromes (细胞色素 ) in cellular
respiration (Nobel Prize in 1931),
? Peter D,Mitchell,proposed the chemiosmotic
theory（ 化学渗透学说） to relate electron flow to
ATP synthesis in all organisms (Nobel Prize in
1978),
? Paul D,Boyer,John E,Walker,enzymatic
mechanism for ATP synthesis (Nobel Prize in
1997),
4.4 Lipid degradation and synthesis
? Konrad Bloch and Feodor Lynen,
pathways for cholesterol and fatty acid
synthesis (Nobel Prize in 1964),
? Michael S,Brown and Joseph L,Goldstein,
regulation of cholesterol biosynthesis
(Nobel Prize in 1985),
4.5 Regulation of Metabolism
? Earl W,Sutherland,Jr.,cAMP as the second
messager for hormones to regulate cell
metabolism (Nobel Prize in 1971),
? Alfred G,Gilman and Martin Rodbell,
involvement of membrane G-proteins in signal
transduction of hormones (Nobel Prize in 1994),
? Edmond H,Fischer and Edwin G,Krebs,
regulation of enzymatic activity by reversible
phosphorylation (Nobel Prize in 1992),
4.6 Photosynthesis
? Hans Fischer,constitution of chlorophyll
(叶绿素 ) and its similarity to heme (Nobel
Prize in 1930),
? Melvin Calvin,Calvin cycle for CO2
assimilation (Nobel Prize in 1961),
? Johann Deisenhofer,Robert Huber,and
Hartmut Michel,3-D structure of a
Photosynthetic reaction center from a
purple bacterium (Nobel Prize in 1988),
4.7 DNA,RNA and Protein synthesis
? Severo Ochoa and Arthur Kornberg,enzymatic
synthesis of RNA and DNA (Nobel Prize in
1959),
? Marshall W,Nirenberg,Har Gobind Khorana,
interpretation of the genetic codes in protein
synthesis (Noble Prize in 1968),
? Francois Jacob,Andre Lwoff,and Jacques
Monod,Mechanisms to switch genes one and
off in prokaryotes (Nobel Prize in 1965),
? David Baltimore,Renato Dulbecco,and Howard
Martin Temin,enzymatic RNA-dependent DNA
synthesis in tumor viruses (Nobel Prize in 1975),
? Barbara McClintock,mobile genetic elements or
transposons (Nobel Prize in 1983),
? Susumu Tonegawa,genetic principle for the
generation of antibody diversity (Nobel Prize in
1987),
? Sidney Altman and Thomas R,Cech,RNA
catalyzed RNA processing (Ribozyme,核酶 )
(Nobel Prize in 1989),
? Richard J,Roberts and Philip A,Sharp,
eukaryotic genes are split and have to be
spliced (剪接 ） after transcription (Noble Prize in
1993),
? Gunter Blobel,intrinsic signals govern protein
localization (Nobel Prize in 1999),
How to study Biochemistry II
? Compare and relate the chemical reactions (the
substrates,the products and the type of conversion)
enzymes,coenzymes,physiological roles,ways of
regulation involved,etc,(This must be similar/related
to that!)
? Understand the classical experiments and thoughts
that led to the revelation of the knowledge described
(why was one awarded the Nobel Prize?),
? Be aware with the degree of speculativeness on
certain models (nothing is 100% certain in science),
? Understand the aspects that need further studies (how
could I win a Nobel Prize?)
Chapter 20
Principles of
Bioenergetics
Bioenergetics (生物能学 ）
the quantitative study of energy
transductions in living cells and the chemical
nature underlying these processes,
一,Bioenergetics and
Thermodynamics
1,Cells need energy to do all
their work
? 形成和保持细胞高度有序的结构 (biosynthesis of
macromolecules),
? 推动所有类型的运动 (mechanical work and
transport),
? 建立跨膜的离子浓度和电荷梯度,
? 保持体温,
? 在某些生物中产生光,
? The,energy industry”(production,storage and
use) is central to the economy of the cell society!
2,Chemical energy is the favorable
energy form for cells to do all their work
? Antoine Lavoisier`s insight on animal respiration
in the 18th century,it is nothing but a slow
combustion of carbon and hydrogen (the same
nature as a lighting candle).(拉瓦锡 1743－ 1794)
? Living cells are generally held at constant
temperature and pressure,chemical energy
(free energy) has to be used by living organisms,
no thermal energy,neither mechanical energy is
available to do work in cells,
? Biological energy transformation obey the two
basic laws of thermodynamics revealed by
physicists and chemists in the 19th century,
energy can neither be created nor be destroyed
(but conserved); energy conversion is never
100% efficient (some will always be wasted in
increasing the disorder or,entropy” of the
universe),
? The free energy concept of thermodynamic is
more important to biochemists than to chemists
(who can always increase the temperature and
pressure to make a reaction to occur!),
3,The free energy (G) concept of
biochemical reactions
(1) Free energy (G),在恒定的温度和压力条件下，一个
生物化学反应或过程可以用来做功的能量的多少。注
意：自由能强调的是反应始态与终态之间的能量变化，
任何体系的绝对自由能是无法测定的。
(2) Free energy change (?G),即产物与反应物之间的
自由能差异。
(3) Gibbs 发现, 在恒定的温度和压力条件下，任何 自发
过程 的自由能都是减少的 (products should have
less free energy than reactants for a reaction to
occur spontaneously,i.e.,?G has a negative
value ).（ 注意,自发性与化学反应的速率没有任何
关系 ）
（ 4） 生物化学中的标准自由变化 (?G'o),value of the
change in free energy under conditions of 298 K
(25oC),1 atm pressure,pH 7.0 (chemists use pH
0,i.e.,the concentration of H+ they use is 1M,
not 10-7 M as biochemists use here) and initial
concentrations of 1 M for all reactants and
products (except H+),
（ 5） The actual free energy chang (?G )depends on
?G'o,temperature,ratio of product and reactant
concentrations (Q),
? ?G = ?G'o + RT ln Q
（ 6） Enzymes only speed up thermodynamically
favorable reactions (having a negative ?G) !
（ 7） ?Go'与 K ' eq 的关系 (the prime again
indicates its biochemical transformation),
at equilibrium,?G = 0,Q = K`eq,thus
? ?Go' = -RT ln K'eq
（ 8） 当两个反应偶联时,?G and ?G‘o 的值
具有加和性 （ additive ） (i.e.,sharing
common intermediates),因此，一个热力
学允许的反应可以驱动一个热力学不利的
反应, 这样的现象在生物化学中经常遇到。
Glucose + Phosphate → Glucose-6-phosphate + H2O
?Go? = +13.8 KJ/mol
ATP + H2O → ADP + Pi
?Go? = -30.5 KJ/mol
二,Phosphate Group
Transfers and ATP
1,ATP水解的标准自由能（ ?Go? ）,
[ATP] = [ADP] = [Pi] = 1mol/L,[H+] = 10-7 mol/L
?Go? = -30.5 KJ/mol
因此我们称 ATP为高能磷酸化合物,而发生断裂的
焦磷酸键称为高能键。 （注意：我们所说的高
能与化学中的高能键是完全不同的两个概念）
2,在细胞中,ATP水解的实际自由能变化（ ?G）
与 ?Go?差别很大,(?G'o is -30.5 kJ/mol; ?G in
cells is -50 to -65 kJ/mol)
? For example,in human erythrocytes the
concentrations of ATP,ADP,and Pi are
2.25,0.25,and 1.65 mM,respectively,the
pH is 7.0 and the temperature is 25° C,
ΔG =ΔG° '+ RT ln [ADP][P i] [ATP]
= -30,500 J/mol + (8.315 J/mol?K)(298 K)ln
[(2.50?10-4)(1.65?10-3)/(2.25?10-3)]
=-30,500 + 2,480ln(1.83?10-4)
=-51.8 (kJ/mol)
3,The ATP molecule is kinetically stable at
pH 7 (i.e.,it has a high activation energy,
?G? for hydrolysis) and enzyme catalysis is
needed for its hydrolysis,
4,ATP is not a long-term storage form of
free energy in living cells,being consumed
within a minute following its formation,A
resting human consumes about 40 kg of
ATP in 24 hours!
5,其他高能磷酸化物和硫酯类化合物,
6,ATP has an intermediate phosphoryl group
transfer potential,thus ADP can accept and
ATP can donate phosphoryl groups,
ATP provides energy by group transfer
(donating a Pi,PPi or AMP to form covalent
intermediates),not by simple hydrolysis,
ATP has an intermediate
phosphoryl group transfer
potential
ATP can transfer a Pi,PPi or AMP to a reactant
7,In the lab,as little as a few picomoles (10-12 mol) of
ATP can be measured using firefly luciferin and
luciferase (荧光素酶 ),using spectroscopic methods,
三,生物主要是通过氧化还原反应的电
子转移获得生物能
1,When electrons flow from a low affinity carrier
(reductant,e.g.,glucose) to a high affinity carrier
(oxidant,e.g.,O2),either in an electric battery or in
a living cell,energy is released and work can be
done,
? Oxidation of energy-rich biological fuels often
means dehydrogenation (catalyzed by
dehydrogenases,脱氢酶 ) from carbons having
various oxidation states,
? In the living cells,electrons are transferred directly
as electrons (between metal ions),as hydrogen
atoms (H++e-),or as a hydride ion (:H- or H++2e-),
生物细胞中氧化还原反应电子转移方式,
1,以电子的形式传递,
呼吸链中细胞色素之间的氧化还原反应。
2,以氢原子的形式传递,
以 FMN或 FAD为氢受体的脱氢反应。
3,以氢负离子（或 H+ + 2e-） 形式传递,
以 NADN+或 NADP+为受体的脱氢反应。
2,Reduction potentials (E) measure affinity for
electrons,
? The affinity for electrons of a compound (in its
oxidized form) is indicated by its reduction potential
(E),
? Standard reduction potential (Eo') of each oxidant
(a constant) is measured by connecting a half-cell
having the oxidized and reduced species of the
redox pair each at 1 M,or 1 atm for gases,pH 7 to
a reference half-cell having 1 M H+ and 1 atm H2,
whose Eo' is arbitrarily assigned as 0.00 V,
? A positive value of Eo' indicates a tendency to
acquire electron from the reference half cell (with
1M H+/1atm H2),
The standard reduction
potential (Eo') of a
conjugate redox pair
is measured by
connecting the sample
half-cell to the H+/H2
reference half-cell,
pH 7 pH 0
? Walther Nernst derived an equation that
relates standard reduction potential (E0) to
reduction potential (E) at any concentration
of oxidized and reduced species in the cell,
在生物化学中用 Eo'取代 Eo
Eo'
3,生物化学反应的自由能变化与电池电动势,
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 ΔGo'=-nFΔEo'
? Acetaldehyde + NADH + H+ → ethanol + NAD+
? The relevant half reactions and their Eo values are,
? (1) Acetaldehyde + 2H+ + 2e- → ethanol
Eo?= -0.197 V
? (2) NAD+ + 2H+ + 2e- → NADH + H+
Eo' = -0.320 V
? For the overall reaction,
ΔEo' = -0.197 V - (-0.320 V) = 0.123 V,
and n is 2,Therefore,
ΔGo' = -nFΔEo' = -2(96.5 kJ/V?mol)(0.123 V) = -23.7
kJ/mol,
5,A few universal carriers collect electrons from the
stepwise oxidation of various substrates,
? Cellular oxidation of a nutrient occurs via stepwise
reactions (pathways) for efficient energy
transduction,
? NAD+,NADP+,FAD,and FMN are universal
reversible electron carriers (as coenzymes of
various enzymes),
? NAD and NADP are dinucleotides able to
accept/donate a hydride ion (with 2e-) for each
round of reduction/oxidation,
? NAD (as NAD+) usually acts in oxidations and
NADP (as NADPH) in reductions,
? NAD and NADP can easily diffuse out of
the enzymes,but FMN and FAD are tightly
bound to the enzymes (thus being called
prosthetic groups,and the complex
proteins being called flavoproteins),
? NADH and FADH2 will be further oxidized
via the respiratory chain for ATP
production,
:H-
Quinonoid
NAD (Nicotinamide Adenine Dinucleotide) and
NADP (Nicotinamide Adenine Dinucleotide
Phosphate)
Nicotinamide
(derived from
niacin)
Benzenoid
(in solution)
Isoalloxazine
FMN (Flavin
mononucleotide) and
FAD (Flavin Adenine
Dinucleotide)
E o' of FAD/FMN often
differs in different flavoproteins,
which are often complex and
contain other inorganic ions to help
electron transfer
异咯嗪环
(derived from
riboflavin)
ATP的
水解和
镁离子
的作用
Carbons have
various
oxidation states,
with
hydrocarbon
being the most
reduced and
CO2 being the
most oxidizaed,
首先，在你们这个年龄应该充满理想和抱负，对知识、科学
和人生有着无限追求。所以，我觉得考研的主要目的是为了进
一步提高自己的知识层次，培养从事科学研究的能力，为实现
更大和更远的目标奠定基础。如果这样，你就应该选一个自己
喜欢的学科专业，立志为其不懈努力，奋斗不止。
其次，可能你对学科专业的认识还很模糊，难以确定自己
喜欢什么，并且近期目标就是考上研究生，那么，就根据自己
的专业知识能力和英语水平，选择比较有把握考上的单位。因
为三年以后如何变化和发展是很难预料的。也许，在这三年中，
你对科学的认识更加深刻，业务知识和科研能力都取得了飞跃
进展，到时考博和出国深造都有可能。往后的发展机遇可能更
多更好。
最后，如果你的目的就是为了研究生毕业后 容易 就业或找一
份好的工作，那么，我认为生物化学和分子生物学专业最
好。一是目前以及在未来一段时间内，这方面的专业人员
还比较短缺，例如，近年来，我们学院来了许多研究生和
博士生，但没有一个生物化学和分子生物学专业的，而我
们学院急需这方面的师资和学术骨干。并且据我了解，全
国普通高校都存在类似问题。二是随着生物技术的发展和
应用，我国生物技术产业将迅速发展，而生物化学和分子
生物学是生物技术的理论基础和技术支撑，所以未来的就
业机会很多。三是生物化学和分子生物学专业比较容易转
行，如你所说的健康和营养问题都离不开生物化学的理论
和技术。 既是 到一些公司搞营销，也属生物化学专业选择
面最广。
以上所述，仅是我个人的看法，还要根据你自己的情况
而定。
The End !
