microsoft powerpoint - chapter-6
TRANSCRIPT
-
8/18/2019 Microsoft PowerPoint - Chapter-6
1/44
13. Bioenergetics and Biochemical
Reaction Types
13.1 Bioener etics and Thermod namics 490
Chapter-6
13.2 Chemical Logic and Common Biochemical
Reactions 495
13.3 Phosphoryl Group Transfers and ATP 501
13.4 Biological Oxidation-Reduction Reactions 512
-
8/18/2019 Microsoft PowerPoint - Chapter-6
2/44
PART II
-
8/18/2019 Microsoft PowerPoint - Chapter-6
3/44
Why we need to study this part ?
Metabolism is a highly coordinated cellular activity in which manymultienzyme systems (metabolic pathways) cooperate to:
1. obtain chemical energy by capturing solar energy or degrading
energy rich nutrients from the environment;
2. convert nutrient molecules into the cell’s own characteristic
molecules, including precursors o macromolecules;
3. polymerize monomeric precursors into macromolecules: proteins,
nucleic acids, and polysaccharides;
4. synthesize and degrade biomolecules required for specialized
cellular functions, such as membrane lipids, intracellularmessengers, and pigments.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
4/44
Energy vs Carbon source
Types of
TrophsEnergy
source
Carbon
source
Microorganisms Plants Animals
Photo-
AutotrophUV light CO2 algae, cyanobacteria,
sulphur bacteria, .. X
Photo – UV light Organics Purple bacteria, green
Heterotroph ac er a…
Chemo–
Autotroph
Inogranics:
NH4+,
NO2-, H2S,
H2, Fe2+
CO2 Nitrification bacteria,Sulphur oxidative
bacteria, hydrogen
producing bacteria…
Chemo–
Heterotroph
Organics Organics Fermentative bacteria,Enterobacteria…
X
-
8/18/2019 Microsoft PowerPoint - Chapter-6
5/44
Auto trophs - (such as photo-synthetic bacteria, green algae, and vascular plants) can
use carbon dioxide from the atmosphere as their sole source of carbon, from which they
construct all their carbon-containing biomolecules (see Fig. 1–5). Some autotrophic
organisms, such as cyanobacteria, can also use atmospheric nitrogen to generate all
their nitrogenous components.
Heterotrophs cannot use atmospheric carbon
dioxide and must obtain carbon from their
environment in the form of relatively complex
organic molecules such as glucose. Multicellular
animals and most microor anisms areheterotrophic,
In our biosphere, autotrophs and heterotrophs
live together in a vast, interdependent cycle in
which autotrophic organisms use atmospheric
carbon dioxide to build their organic biomolecules,
some of them generating oxygen from water inthe process. Heterotrophs in turn use the organic
products of autotrophs as nutrients and return
carbon dioxide to the atmosphere Interdependent Cycle
-
8/18/2019 Microsoft PowerPoint - Chapter-6
6/44
Metabolism, the sum of all the chemical transformations taking place in a cell or
organism, occurs through a series of enzyme-catalyzed reactions that constitute
metabolic pathways. Each of the consecutive steps in a metabolic pathway bringsabout a specific, small chemical change, usually the removal, transfer, or addition of a
particular atom or functional group.
Metabolites are series of metabolic intermediates formed during conversion of the
precursor into a product.
Catabolism is the de radative hase of metabolism in which or anic nutrient molecules
Definitions
(carbohydrates, fats, and proteins) are converted into smaller, simpler end products
(such as lactic acid, CO2, NH3). Catabolic pathways release energy, some of which is
conserved in the formation of ATP and the electron carriers (NADH, NADPH, and
FADH2); the rest is lost as heat.
Anabolism, also called biosynthesis, small, simple precursors are built up into larger
and more complex molecules, including lipids, polysaccharides, proteins, and nucleic
acids. Anabolic reactions require an input of energy, generally in the form of the
phosphoryl group transfer potential of ATP and the reducing power of NADH, NADPH,
and FADH2.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
7/44
FIGURE 3 Energy relationships
between catabolic and anabolic
path ways.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
8/44
Three types of nonlinear metabolic pathways.
Anabolism
Catabolism
-
8/18/2019 Microsoft PowerPoint - Chapter-6
9/44
13. Bioenergetics and Biochemical
Reaction Types
13.1 Bioener etics and Thermod namics 490 13.2 Chemical Logic and Common Biochemical
Reactions 495
13.3 Phosphoryl Group Transfers and ATP 501
13.4 Biological Oxidation-Reduction Reactions 512
-
8/18/2019 Microsoft PowerPoint - Chapter-6
10/44
13.1 Bioenergetics and Thermodynamics
Bioenergetics is the quantitative study of energy transductions—changes of
one form of energy into an other—that occur in living cells, and of the nature
and function of the chemical processes underlying these transductions.
Biological Energy Transformations Obey the Laws of Thermodynamics
Gibbs f ree energy, G, expresses the amount of energy capable of doing work during
a reaction at constant temperature and pressure. When a reaction proceeds with the
release of free energy (that is, when the system changes so as to possess less free
energy), the free-energy change, G, when 0 is said to be ender on ic reactions.Enthalpy, H, is the heat content of the reacting system. It reflects the number and kinds
of chemical bonds in the reactants and products. 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 H 0 when entropy increases and DH, as noted above, < 0 when heat is released by
the system to its surroundings DG
-
8/18/2019 Microsoft PowerPoint - Chapter-6
11/44
Free energy change, G
When a reacting system is not equilibrium,the tendency to move toward
equilibrium represents a driving force,the magnitude of which can beexpressed as the free-energy changefor the reaction, G.
< 0: exergonic: release free energy
> 0: endergonic: require energy
Ea
, – transition state-
In biosystem: living cells andorganisms, however, are opensystems, exchanging both materialsand energy with their surroundings;
living systems are never at equilibriumwith their surroundings.
G
Notes:
Endogenic : action or object coming from inside
Exogenic : action or object coming from out side
-
8/18/2019 Microsoft PowerPoint - Chapter-6
12/44
Standard (transformed) free-energy changes, G’o
KEY CONVENTION: For
convenience of calculations,
biochemists define a standard state
different from that used in
chemistry and physics: in the
biochemical standard state, [H+] is
[C]c[D]d
[A]a[B]bKeq=
DG’o
= -RT ln K’eq
0 10- M (pH 7.0) and [H2O] is 55.5M. For reactions that involve Mg+2
(which include most of those with
ATP as a reactant), [Mg2+] in
solution is commonly taken to be
constant at 1 mM.
condition: Temp. 25oC = 298K, 1 atm
(101.3 kPa), concentration of reactants
= 1 M. G’o : biochemical reaction does not
occur in 1 M concentration, thus it is
the “transformed” Go
.K’eq thus is the “transformed” Keq
-
8/18/2019 Microsoft PowerPoint - Chapter-6
13/44
Actual Free-Energy Changes (
G ) Depend on Reactant
and Product Concentrations
aA + bB cC+ dDv1v2
DG =DG’o + RT ln[products]
[reactants]
R : gas constant = 8.315 J/mol or = 1.987 cal/mol
T : absolute temperature (Kenvin temp (Ko
) , 25o
C = 298o
K)
-
8/18/2019 Microsoft PowerPoint - Chapter-6
14/44
Standard Free-Energy Changes Are Additive
In the case of two sequential chemical reactions, A B and B C, each
reaction has its own equilibrium constant and each has its characteristic
standard free energy change, DG’o 1 and DG’o 1.
For an example
The overall reaction is exergonic. In this case, energy stored in ATP is used to drive the
synthesis of glucose 6-phosphate, even though its formation from glucose and
inorganic phosphate (Pi) is endergonic.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
15/44
SUMMARY 13.1 Bioenergetics and Thermodynamics
1. Living cells constantly perform work. They require energy for maintainingtheir highly organized structures, synthesizing cellular components,
generating electric currents, and many other processes.
2. Bioenergetics is the quantitative study of energy relationships and energy
conversions in biological systems. Biological energy transformations obey
the laws of thermodynamics
3. All chemical reactions are influenced by two forces: the tendency to achieve
the most stable bonding state (for which enthalpy, H, is a useful expression)
and the tendency to achieve the highest degree of randomness, expressed
as entropy, S. The net driving force in a reaction is DG, the free-energy
change, which represents the net effect of these two factors: DG =D H-TDS.
4. The standard transformed free-energy change, DG’o
, is a physical constantthat is characteristic for a given reaction and can be calculated from the
equilibrium constant for the reaction: DG’o = RT ln K’eq.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
16/44
SUMMARY 13.1 Bioenergetics and Thermodynamics
5. The actual free-energy change, G, is a variable that depends on DG’o and on
the concentrations of reactants and products: G = G’o + RTln
([products]/[reactants]).
6. When G is large and negative, the reaction tends to go in the forward direction;
when DG is large and positive, the reaction tends to go in the reverse direction;
and when G = 0, the system is at equilibrium.
-.the reaction occurs. Free-energy changes are additive; the net chemical reaction
that results from successive reactions sharing a common intermediate has an
overall free-energy change that is the sum of the DG values for the individual
reactions.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
17/44
13.2 Chemical Logic and Common Biochemical Reactions
Cellular chemistry does not encompass every kind of reaction learned in a typical
organic chemistry course. Biological reactions are determined by (1) their relevance
to that particular metabolic system and (2) their rates.
Most of the reactions in living cells fall into one of general categories:
(1) reactions that make or break carbon–carbon bonds;
(2) internal rearrangements, isomerizations, and eliminations;
(3) free-radical reactions;
(4) group transfers;
ox a on-re uc ons.
Note that: the five reaction types are not mutually exclusive; for example, an
isomerization reaction may involve a free -radical intermediate.
Two basic chemical principles:
1) a covalent bond can be broken in two general ways: homolytic cleavage and
heterolytic cleavage;
2) biochemical reactions involve interactions: nucleophiles or electrophiles.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
18/44
FIGURE 13–1 Two mechanisms
for cleavage of a C—C or C—H
bond. In a homolytic cleavage,
each atom keeps one of the
bonding electrons, resulting in the
formation of carbon radicals(carbons having unpaired
electrons) or uncharged hydrogen
atoms. In a heterolytic cleavage,
one of the atoms retains both
bonding electrons. This can result
in the formation of carbanions,
carbocations, protons, or hydrideion.
Formation of a C C bond involves
the combination of a nucleophilic
carbanion and an electrophilic
carbocation. Carbanions and
carbocations are generally so
unstable that their formation as
reaction intermediates can be
energetically inaccessible even
with enzyme catalysts.
(Carbon –anion )
(Carbon –cation )
-
8/18/2019 Microsoft PowerPoint - Chapter-6
19/44
A anion donates electrons A cation pulls electrons
FIGURE 13–2 Common
nucleophiles and electrophiles
in biochemical reactions.
Chemical reaction mechanisms,
which trace the formation and
breakage of covalent bonds, are
communicated with dots
and curved arrows, a convention
known informally as “electron
pushing.” A covalent bond
consists of a shared pair of
electrons. Non-
bonded electrons important to
the reaction mechanism are
designated
by dots (:). For movement of asingle electron (as in a free
radical reaction), a single-headed
(fishhook-type) arrow is used ( ).
Most reaction steps involve an
unshared electron pair.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
20/44
The carbon of a carbonyl group has a
partial positive charge due to the
electron-withdrawing property of the
carbonyl oxygen, and thus is an
electrophilic carbon.
FIGURE 13–3 Chemical properties of carbonyl groups.
(a) The carbon atom of a carbonyl group is an electrophi le by virtue of the electron
withdrawing capacity of the electro negative oxygen atom, which results in a
resonance hybrid structure in which the carbon has a partial positive charge. (
(b) Within a molecule, delocalization of electrons into a carbonyl group stabilizes acarbanion on an adjacent carbon, facilitating its formation.
(c) Imines function much like carbonyl groups in facilitating electron withdrawal.
(d) Carbonyl groups do not always function alone; their capacity as electron sinks often
is augmented by interaction with either a metal ion (Me2+, such as Mg2+) or a
general acid (HA)
-
8/18/2019 Microsoft PowerPoint - Chapter-6
21/44
aldolase
synthesis of citrate in the
citric acid cycle (TCA)
converts a six-carbon
compound to two three-
carbon compounds in
glycolysis
For both the aldol condensation and the Claisen condensation, a carbanion servesas nucleophile and the carbon of a carbonyl group serves as electrophile. The carbanion
is stabilized in each case by another carbonyl at the adjoining carbon.
In the decarboxylation reaction, a carbanion is formed on the carbon shaded blue as
the CO2 leaves. The reaction would not occur at an appreciable rate without the
stabilizing effect of the carbonyl adjacent to the carbanion carbon.
FIGURE 13–4 Some
common reactions that
form and break C—C
bonds in biological
systems.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
22/44
Internal Rearrangements, Isomerizations, and Eliminations
FIGURE 13–5 Carbocations in
carbon–carbon bond
formation. In one of the earlysteps in cholesterol
biosynthesis, the enzyme prenyl
transferase catalyzes
condensation of isopentenyl
pyrophosphate and dimethylallyl
pyrop osp a e o orm geranypyrophosphate (see Fig. 21–36).
The reaction is initiated by
elimination of pyrophosphate
from the dimethylallyl
pyrophosphate to generate a
carbocation, stabilized byresonance with the adjacent
CPC bond.Polymeration
-
8/18/2019 Microsoft PowerPoint - Chapter-6
23/44
Isomerization
Elimination
FIGURE 13–6 Isomerization and elimination reactions.
(a) The conversion of glucose 6-phosphate to fructose 6-phosphate, catalyzed byphosphohexose isomerase.
(b) The reaction proceeds through an enediol intermediate. B1 and B2 are ionizable
groups on the enzyme; they are capable of donating and accepting protons (acting as
general acids or general bases) as the reaction proceeds. Pink screens indicate
nucleophilic groups; blue, electrophilic.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
24/44
Free radical reactions
– ree ra ca – n a e ecar oxy a on reac on.
Groups transfer reactions
-
8/18/2019 Microsoft PowerPoint - Chapter-6
25/44
FIGURE 13–8 Alternat ive ways of showing the structure of inorganic
orthophosphate (Pi) (a) In one (inadequate) representation, three oxygens are single-
bonded to phosphorus, and the fourth is double-bonded, allowing the four different
resonance structures shown here. (b) The resonance structures can be representedmore accurately by showing all four phosphorus–oxygen bonds with some double-bond
character; the hybrid orbitals so represented are arranged in a tetrahedron with P at its
center. (c) When a nucleophile Z (in this case, the —OH on C-6 of glucose) attacks ATP,
it displaces ADP (W). In this SN2 reaction, a pentacovalent intermediate (d) forms
transiently.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
26/44
FIGURE 13–10 An ox idation-
reduction reaction.
FIGURE 13–9 The oxidation states of
carbon in biomolecules. Each
compound is formed by oxidation of the
red carbon in the compound shown
immediately above. Carbon dioxide isthe most highly oxidized form of carbon
found in living systems.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
27/44
SUMMARY 13.2 Chemical Logic and Common Biochemical
Reactions
■ Living systems make use of a large number of chemical reactions that can be
classified into general types.
■ Carbonyl groups play a special role in reactions that form or cleave C C bonds.
Carbanion intermediates are common and are stabilized by adjacent carbonyl groups
or, less often, by imines or certain cofactors.
■ A re-distribution of electrons can produce internal rearrangements, isomerizations,
and eliminations. Such reactions include intramolecular oxidation-reduction, change in
cis-trans arrangement at a double bond, and transposition of double bonds.
■ Homolytic cleavage of covalent bonds to generate free radicals occurs in some
pathways, such as in certain isomerization, decarboxylation, reductase, and
rearrangement reactions.
■ Phosphoryl transfer reactions are an especially important type of group transfer in
cells, required for the activation of molecules for reactions that would otherwise be highlyunfavorable.
■ Oxidation-reduction reactions involve the loss or gain of electrons: one reactant
gains electrons and is reduced, while the other loses electrons and is oxidized.
Oxidation reactions generally release energy and are important in catabolism.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
28/44
13.3 Phosphoryl Group Transfers and ATP
ATP Donates Phosphoryl, Pyrophosphoryl,
and Adenylyl Groups
18O: isotope
-
8/18/2019 Microsoft PowerPoint - Chapter-6
29/44
Free Energy from hydrolysis of ATP
+ H20
(-)30.5 kJ/mol
H+ và
a –b phosphoanhydride: 45.6 kJ/molg -b phosphoanhydride: 30.5 kJ/mol
-
8/18/2019 Microsoft PowerPoint - Chapter-6
30/44
BPP
+ H20
+ Pi
Other compounds are energy rich
: Bis-phosphoglycerate
- . mo
Bis-phosphoglycerate
-
8/18/2019 Microsoft PowerPoint - Chapter-6
31/44
+ H20
PEP: Phosphoenolpyruvate
+ Pi
Other compounds are energy rich
Phosphoenolpyruvate
- . mo
-
8/18/2019 Microsoft PowerPoint - Chapter-6
32/44
-
8/18/2019 Microsoft PowerPoint - Chapter-6
33/44
FIGURE 13–19 Ranking of biological phosphate
compounds by standard free energies of hydrolysis.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
34/44
SUMMARY 13.3 Phosphoryl Group Transfers and ATP1. ATP is the chemical link between catabolism and anabolism. It is the energy
currency of the living cell. The exergonic conversion of ATP to ADP and Pi or to AMP
and PPi, is coupled to many endergonic reactions and processes.
2. Direct hydrolysis of ATP is the source of energy in some processes driven byconformational changes, but in general it is not ATP hydrolysis but the transfer of a
phosphoryl, pyrophosphoryl, or adenylyl group from ATP to a substrate or enzyme
that couples the energy of ATP breakdown to endergonic transformations of
substrates.
3. Through these group transfer reactions, ATP provides the energy for anabolic
, ,transport of molecules and ions across membranes against concentration gradients
and electrical potential gradients.
4. To maintain its high group transfer potential , ATP concentration must be held far
above the equilibrium concentration by energy-yielding reactions of catabolism.
5. Cells contain other metabolites with large, negative, free energies of hydrolysis,
including phosphoenolpyruvate, 1,3-bisphosphoglycerate, and phosphocreatine.These high-energy compounds, like ATP, have a high phosphoryl group transfer
potential. Thioesters also have high free energies of hydrolysis.
6. ■ Inorganic polyphosphate, present in all cells, may serve as a reservoir of
phosphoryl groups with high group transfer potential.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
35/44
1. Directly as electrons. For example, the Fe2"/Fe3"redox pair can transfer an
electron to the Cu"/Cu2" redox pair
2. As hydrogen atoms. Recall that a hydrogen atom consists of a proton (H")
and a single electron (e-). In this case we can write the general equation
13.4 Biological Oxidation-Reduct ion Reactions
3 As a hydride ion (:H-), which has two electrons.This occurs in the case of
NAD-linked dehydrogenases, described below
4. Through direct combination with oxygen. In this case, oxygen combines
with an organic reductant and is covalently incorporated in the product, as
in the oxidation of a hydrocarbon to an alcohol:
-
8/18/2019 Microsoft PowerPoint - Chapter-6
36/44
NADH and NADPH act with dehydrogenases as soluble electron
carriers
FIGURE 13–24 NAD and NADP. (a) Nicotinamide adenine dinucleotide, NAD +, and its
phosphorylated analog NADP+ undergo reduction to NADH and NADPH, accepting a
hydride ion (two electrons and one proton) from an oxidizable substrate. The hydride ion
is added to either the front (the A side) or the back (the B side).
-
8/18/2019 Microsoft PowerPoint - Chapter-6
37/44
-
8/18/2019 Microsoft PowerPoint - Chapter-6
38/44
FADH2
-
8/18/2019 Microsoft PowerPoint - Chapter-6
39/44
-
8/18/2019 Microsoft PowerPoint - Chapter-6
40/44
SUMMARY 13.4 Biological Oxidation-Reduction Reactions
1. In many organisms, a central energy-conserving process is the stepwise oxidation of
glucose to CO2,in which some of the energy of oxidation is conserved in ATP as
electrons are passed to O2.2. Biological oxidation-reduction reactions can be described in terms of two half-
reactions, each with a characteristic standard reduction potential, E’o.
3. The standard free-energy change for an oxidation-reduction reaction is directly
proportional to the difference in standard reduction potentials of thetwo half-cells:
Go ' = -n J E’o
4. Many biological oxidation reactions are dehydrogenations in which one or two
hydrogen atoms (H+ + e-) are transferred from a substrate to a hydrogen acceptor .
Oxidation-reduction reactions in living cells involve specialized electron carriers.
5. NAD and NADP are the freely diffusible coenzymes of many dehydrogenases. Both
NAD+ and NADP + accept 02 electrons and 01 proton.
6. FAD and FMN, the flavin nucleotides, serve as tightly bound prosthetic groups offlavoproteins. They can accept either 01 or 02 electrons and 01 or 02 protons.
Flavoproteins also serve as light receptors in crytochromes and photolyases.
-
8/18/2019 Microsoft PowerPoint - Chapter-6
41/44
Oxidative phosphorylation or ATP synthesis by ATPsynthase
driven by the protons motive force generated through the
electrons transport chain
F1
ATP synthase
(F-type: FoF1- ATPase)
Fo
-
8/18/2019 Microsoft PowerPoint - Chapter-6
42/44
FIGURE 19–19 Chemiosmotic model. In this simple representation of the
chemiosmotic theory applied to mitochondria, electrons from NADH and other
oxidizable substrates pass through a chain of carriers arranged asymmetrically in theinner membrane. Electron flow is accompanied by proton transfer across the membrane,
producing both a chemical gradient ( pH) and an electrical gradient ( y). The inner
mitochondrial membrane is impermeable to protons; protons can reenter the matrix only
through proton-specific channels (Fo). The proton-motive force that drives protons back
into the matrix provides the energy for ATP synthesis, catalyzed by the F1Fo complex.
ATP synthase
-
8/18/2019 Microsoft PowerPoint - Chapter-6
43/44
-
8/18/2019 Microsoft PowerPoint - Chapter-6
44/44
SUMMARY 19.2 ATP Synthesis
■ The flow of electrons through Complexes I, III, and IV results in pumping of protons
across the inner mitochondrial membrane, making the matrix alkaline relative to the
intermembrane space. This proton gradient provides the energy (the proton-motive
force) for ATP synthesis from ADP and Pi by FoF1- ATP synthase in the innermembrane.
■ ATP synthase carries out “rotational catalysis,” in which the flow of protons through Fo
causes each of three nucleotide-binding sites in F1 to cycle from (ADP + Pi)–bound to
ATP-bound to empty conformations.
■ ATP formation on the enzyme requires little energy; the role of the proton-motive force
.
■ The ratio of ATP synthesized per reduced to H2O (the P/O ratio) is about 2.5 when
electrons enter the respiratory chain at Complex I (NADH), and 1.5 when electrons enter
at ubiquinone. (FADH2)
■ Energy conserved in a proton gradient can drive solute transport uphill across a
membrane.
■ The inner mitochondrial membrane is impermeable to NADH and NAD+ but NADH
equivalents are moved from the cytosol to the matrix by either of two shuttles. NADH
equivalents moved in by the malate-aspartate shuttle enter the respiratory chain at
Complex I and yield a P/O ratio of 2.5; those moved in by the glycerol 3-phosphate
shuttle enter at ubiquinone and give a P/O ratio of 1.5.