Princípios Físicos Aplicados à Fisiologia...
Transcript of Princípios Físicos Aplicados à Fisiologia...
Princípios Físicos Aplicados à Fisiologia (PGF5306-1)
Prof. Adriano Mesquita AlencarDep. Física Geral
Instituto de Física da USP
EnergiaAula 11
B02
calorimeter9 (Fig. 1.11) is used to measure the heat given off in theoxidation of a combustible substance like food, and nutritionistsrefer to tables of combustion heats in planning a diet.
The study of energy transformations is called thermodynamics.It is a hierarchical science – the more advanced concepts assumeknowledge of the more basics ones. To be ready to tackle the moredifficult but more interesting topics in later chapters, let’s use thismoment to develop an understanding of what is being measured inthe bomb calorimeter. We know from experience that the oxidation(burning) of wood gives off heat. Some types of wood are useful forbuilding fires because they ignite easily (e.g. splinters of dry pine);others are useful because they burn slowly and give off a lot of heat(e.g. oak). The amount of heat transferred to the air per unit volumeof burning wood depends on the density of the wood and its struc-ture. The same is true of food. Fine, but this has not told us whatheat is.
It is the nature of science to define terms as precisely as possibleand to formalize usage. Accepted definitions are importantfor minimizing ambiguity of meaning. What we need now is a
Fig. 1.11 Schematic diagram of a bomb calorimeter. A sample is placed in the reaction
chamber. The chamber is then filled with oxygen at high pressure (>20 atm) to ensure
that the reaction is fast and complete. Electrical heating of a wire initiates the reaction.
The increase in water temperature resulting from the combustion reaction is recorded,
and the temperature change is converted into an energy increase. The energy change is
divided by the total amount of substance oxidized, giving units of J g!1 or J mol!1.
Insulation helps to prevent the escape of the heat of combustion, increasing the accuracy
of the determination of heat released from the oxidized material. Based on diagram on
p. 36 of Lawrence et al. (1996).
9 But one of many different kinds of calorimeter. The instrument used to measure theenergy given off in an atom smasher is called a calorimeter. In this book we discuss abomb calorimeter, isothermal titration calorimeter, and differential scanningcalorimeter.
14 ENERGY TRANSFORMATION
sábado, 5 de outubro de 13
Princípios Físicos Aplicados à Fisiologia (PGF5306-1)
sábado, 5 de outubro de 13
Entalpia, H
R, é uma constante universal, 8.3145 J/K mol
calorimeter9 (Fig. 1.11) is used to measure the heat given off in theoxidation of a combustible substance like food, and nutritionistsrefer to tables of combustion heats in planning a diet.
The study of energy transformations is called thermodynamics.It is a hierarchical science – the more advanced concepts assumeknowledge of the more basics ones. To be ready to tackle the moredifficult but more interesting topics in later chapters, let’s use thismoment to develop an understanding of what is being measured inthe bomb calorimeter. We know from experience that the oxidation(burning) of wood gives off heat. Some types of wood are useful forbuilding fires because they ignite easily (e.g. splinters of dry pine);others are useful because they burn slowly and give off a lot of heat(e.g. oak). The amount of heat transferred to the air per unit volumeof burning wood depends on the density of the wood and its struc-ture. The same is true of food. Fine, but this has not told us whatheat is.
It is the nature of science to define terms as precisely as possibleand to formalize usage. Accepted definitions are importantfor minimizing ambiguity of meaning. What we need now is a
Fig. 1.11 Schematic diagram of a bomb calorimeter. A sample is placed in the reaction
chamber. The chamber is then filled with oxygen at high pressure (>20 atm) to ensure
that the reaction is fast and complete. Electrical heating of a wire initiates the reaction.
The increase in water temperature resulting from the combustion reaction is recorded,
and the temperature change is converted into an energy increase. The energy change is
divided by the total amount of substance oxidized, giving units of J g!1 or J mol!1.
Insulation helps to prevent the escape of the heat of combustion, increasing the accuracy
of the determination of heat released from the oxidized material. Based on diagram on
p. 36 of Lawrence et al. (1996).
9 But one of many different kinds of calorimeter. The instrument used to measure theenergy given off in an atom smasher is called a calorimeter. In this book we discuss abomb calorimeter, isothermal titration calorimeter, and differential scanningcalorimeter.
14 ENERGY TRANSFORMATION
�H = �U +RT�n
Em um experimento dessa bomba de calorímetro com
Etanol, a 298K e volume constante, 1368 kJ/mol de
calor é liberado
C2H5OH(`) + 3O2(g) ! 2CO2(g) + 3H2O(`)
sábado, 5 de outubro de 13
Entalpia, H�H = �U +RT�n
�H = �U + 298 · 8.3145�n
�H = �U + 2478�n
�n = 2� 3 = 1
�H = �1368000� 2478
Se a variação de entalpia é negativo o processo é exotérmico. Caso contrario o processo é
endotérmico
C2H5OH(`) + 3O2(g) ! 2CO2(g) + 3H2O(`)
(J/mol)
sábado, 5 de outubro de 13
Entalpia, H
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
Liquido para Gas = 277
((5*415+346+358+464)+277)+3*498
C = O ! 1077 em Monoxido
C = O ! 805 em Dioxido
C �O ! 358
O �H ! 464
H � Cl ! 432
C � C ! 346
C = C ! 602
C �H ! 415
H �H ! 436
O = O ! 498
Liquido para Gas = 41
(2*2*805+6*464+(3*41))
ΔHο= -1113 (saindo do estado liquido)
C2H5OH(`) + 3O2(g) ! 2CO2(g) + 3H2O(`)
ΔHο= -1267 (estado gasoso para todos)
ΔHο= -1368 kJ/mol (Valor de Tabela)
sábado, 5 de outubro de 13
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
C2H5OH(`) + 3O2(g) ! 2CO2(g) + 3H2O(`)En
talp
ia
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
liquidogás
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
gásgás
+277
+4737
6H + 2C + 7O
átomos
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
gás gás
-6004
C
H
H
H
C
H
H
O
H
+ 3 ( OO )�H
+ 2 ( CO O ) + 3 ( O H
H
)
1
1
gás liquido
-123
sábado, 5 de outubro de 13
Bioquímica
• Aproximadamente 1/2 da massa seca do corpo humano é de proteinas• O estado nativo das proteínas é “folded”, empacotado - uma espécie de cristal orgânico• Mesmo nesse estado existe flutuação na estrutura do caroço central.• Estado empacotado - parecido com solido• Estado desempacotado - parecido com liquido
sábado, 5 de outubro de 13
ideal case all amino acid side chains are completely exposed tosolvent (Table 2.4).
The non-covalent interactions that stabilize folded protein struc-ture (or double-stranded DNA or folded RNA structure) can be“broken” in a number of ways. One is by adding heat. If all the non-covalent bonds break simultaneously, in an all-or-none fashion(“cooperative” unfolding), then there are in essence just two states ofthe protein: the folded state and the unfolded state. The transitionfrom the folded state to the unfolded state is like melting. Soinducing the unfolding of protein by heat or some other means issomething like melting a solid. This is true even if one is workingnot with a mass of freeze-dried protein but with folded proteinsdissolved in aqueous solution. The cooperativity of the transition, theall-or-none character of going from being folded to being unfolded,
Table 2.3. Characteristics of hydrogen bonds of biological importance
Bond typeMean bonddistance (nm) Bond energy (kJ mol!1)
O–H . . .O 0.270 !22O–H . . .O! 0.263 !15O–H . . .N 0.288 !15 to !20N"–H . . .O 0.293 !25 to !30N–H . . .O 0.304 !15 to !25N–H . . .N 0.310 !17HS–H . . .SH2 — !7
The data are from Watson (1965).
Table 2.2. Energetics of non-covalent interactions betweenmolecules
Type of interaction Equation
Approximatemagnitude(kcal mol!1)
Ion–ion E# q1q2/Dr 14Ion–dipole E# q„!/Dr2 !2 to "2Dipole–dipole E#„1„2!
0/Dr3 !0.5 to "0.5Ion–induced dipole E# q2fi/2Dr2r4 0.06Dispersion E# 3h”fi2/4r6 0 to 10
a Charge q1 interacts with charge q2 at a distance r in medium of dielectric D.b Charge q interacts with dipole „ at a distance r from the dipole in medium of dielectric D. !and !0 are functions of the orientation of the dipoles.
c Dipole „1 interacts with dipole „2 at an angle q relative to the axis of dipole „2 and adistance r from the dipole in medium of dielectric D.
d Charge q interacts with molecule of polarizability at fi distance r from the dipole in mediumof dielectric D.
e Charge fluctuations of frequency ” occur in mutually polarizable molecules of polarizabilityfi separated by a distance r.
The� data� are� from� Table� 1.1� of� van� Holde� (1985).
SOME EXAMPLES FROM BIOCHEMISTRY 43
1 kcal = 4.18 kJ
sábado, 5 de outubro de 13
Bioquímica
ideal case all amino acid side chains are completely exposed tosolvent (Table 2.4).
The non-covalent interactions that stabilize folded protein struc-ture (or double-stranded DNA or folded RNA structure) can be“broken” in a number of ways. One is by adding heat. If all the non-covalent bonds break simultaneously, in an all-or-none fashion(“cooperative” unfolding), then there are in essence just two states ofthe protein: the folded state and the unfolded state. The transitionfrom the folded state to the unfolded state is like melting. Soinducing the unfolding of protein by heat or some other means issomething like melting a solid. This is true even if one is workingnot with a mass of freeze-dried protein but with folded proteinsdissolved in aqueous solution. The cooperativity of the transition, theall-or-none character of going from being folded to being unfolded,
Table 2.3. Characteristics of hydrogen bonds of biological importance
Bond typeMean bonddistance (nm) Bond energy (kJ mol!1)
O–H . . .O 0.270 !22O–H . . .O! 0.263 !15O–H . . .N 0.288 !15 to !20N"–H . . .O 0.293 !25 to !30N–H . . .O 0.304 !15 to !25N–H . . .N 0.310 !17HS–H . . .SH2 — !7
The data are from Watson (1965).
Table 2.2. Energetics of non-covalent interactions betweenmolecules
Type of interaction Equation
Approximatemagnitude(kcal mol!1)
Ion–ion E# q1q2/Dr 14Ion–dipole E# q„!/Dr2 !2 to "2Dipole–dipole E#„1„2!
0/Dr3 !0.5 to "0.5Ion–induced dipole E# q2fi/2Dr2r4 0.06Dispersion E# 3h”fi2/4r6 0 to 10
a Charge q1 interacts with charge q2 at a distance r in medium of dielectric D.b Charge q interacts with dipole „ at a distance r from the dipole in medium of dielectric D. !and !0 are functions of the orientation of the dipoles.
c Dipole „1 interacts with dipole „2 at an angle q relative to the axis of dipole „2 and adistance r from the dipole in medium of dielectric D.
d Charge q interacts with molecule of polarizability at fi distance r from the dipole in mediumof dielectric D.
e Charge fluctuations of frequency ” occur in mutually polarizable molecules of polarizabilityfi separated by a distance r.
The� data� are� from� Table� 1.1� of� van� Holde� (1985).
SOME EXAMPLES FROM BIOCHEMISTRY 43
sábado, 5 de outubro de 13
results from the concurrent breaking of a large number of weakinteractions. In water, these interactions are hydrogen bonds; inproteins, they are the several kinds mentioned above. The meltingof pure water or any other pure solid is a cooperative phenomenon.That is, melting occurs at a single or over a very narrow range oftemperatures, not over a broad range. The same is true of coop-erative protein unfolding or the melting of DNA.
A number of experimental studies have been carried out tomeasure the energy required to break a hydrogen bond at roomtemperature. This is pertinent not only to the unfolding of proteinsbut also to the “melting” of double-stranded DNA, which is heldtogether by hydrogen bonds. Estimates of the bond energy vary, but areasonable and generally agreed rough figure is 1kcal mol!1. Indi-vidual hydrogen bonds are weak; collections can be quite strong.
In terms of Eqn. (2.10), the enthalpy of the folded state of aprotein is H"
F, the enthalpy of the unfolded state is H"U, and the dif-
ference, H"U ! H"
F, is the enthalpy of denaturation or unfolding, 1Hd".
In this case the folded state of the protein is the reference state, as theenthalpy of the unfolded state is measured with respect to it. Whatis this enthalpy difference? As discussed above, the enthalpy changefor a process is equal to the heat absorbed by the system at constantpressure, and the rigid folded state of a protein can be pictured as asolid, and the flexible unfolded state as a liquid. So the enthalpydifference between the unfolded and folded states of a protein is theamount of heat needed to unfold the protein. As we shall see, themagnitude of that heat depends on the temperature.
Table 2.4. Principal features of protein structure
Folded (native) stateUnfolded (denatured)state
Highly ordered polypeptidechain
Highly disordered chain– “random coil”
Intact elements of secondarystructure, held together byhydrogen bonds
No secondary structure
Intact tertiary structure contacts,as in an organic crystal, heldtogether by van der Waalsinteractions
No tertiary structure
Limited rotation of bonds in theprotein core
Free rotation of bondsthroughout polypep-tide chain
Desolvated side chains in proteincore
Solvated side chains
Compact volume Greatly expandedvolume
44 THE FIRST LAW OF THERMODYNAMICS
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The temperature at which a protein unfolds (or double-strandedDNA melts) is called the melting temperature, Tm. This temperaturedepends not only on the number and type of non-covalent bonds inthe folded state but also on the pH and other solution conditions. Tmalso depends on the pressure, but most biological science experi-ments are done at 1 atm pressure. In the case of proteins, changingthe pH of solution changes the net charge on the protein surface.This can have a marked impact on Tm and 1H!
d, as shown in Fig. 2.7for the example of hen egg white lysozyme, a well-studied smallglobular protein. The figure also illustrates that the slope of 1H!
against Tm for this protein is more or less constant throughout thepH range shown.
Above we saw how a bomb calorimeter can be used to obtainthermodynamic information. Here we introduce isothermal titra-tion calorimetry (ITC)12 and explain how it can be used to measurethe enthalpy of a biochemical process (Fig. 2.8). By Eqn. (2.10) theheat absorbed at constant pressure measures the enthalpy change.Suppose, for example, we are interested in the energetics of thebinding of the Fc portion of immunoglobulin G (IgG), important inhumoral immunity and biotechnology, to soluble protein A, a bac-terial protein. We need not be concerned at the moment just whichpart of IgG the Fc portion of is: we just need to know that antibodymolecules can be dissected into components and that the Fc portionis one of them. The thermodynamic states of interest here are theunbound state, where protein A is free in solution, and the boundstate, where protein A is physically associated with Fc. The heatexchanged at constant pressure upon injection of protein A into acalorimetric cell containing the antibody can thus be used todetermine 1Hb
!, the enthalpy of binding (under standard state con-ditions). The heat of injection will change as the number of vacantbinding sites decreases.
Fig. 2.7 Enthalpy of unfolding of hen
egg white lysozyme as a function of
transition temperature. Filled
symbols: intact lysozyme. Open
symbols: lysozyme in which one of
the four native disulfide bonds has
been removed. When folded, 3-SS
lysozyme closely resembles the
native state of intact lysozyme.
Change in transition temperature
was induced by a change of pH.
Note that 1H is approximately
linear in Tm. The data are from
Cooper et al. (1991).
12 The isothermal titration calorimeter was first described in 1922 by Theophilede Donder, founder of the Brussels School of thermodynamics.
SOME EXAMPLES FROM BIOCHEMISTRY 45
sábado, 5 de outubro de 13
What if we’re interested in the energetics of an enzyme bindingto its substrate? This can be measured if a suitable substrate analogcan be found or the enzyme can be modified. For instance, ITC hasbeen used to measure the enthalpy of binding of a small compoundcalled 20-cytidine monophoshate (20CMP) to ribonuclease A, whichhydrolyzes RNA to its component nucleotides. 20CMP binds to andinhibits the enzyme. If the enzyme of interest is, say, a proteinphosphatase with a nucleophilic cysteine in the active site, muta-tion of the Cys to Ser or Asn will abolish catalytic activity, as in theN-terminal domain of the cytoskeleton-associated protein tensin,and the energetics of binding can be studied. A deeper under-standing of binding will be sought in Chapters 5 and 7.
If you’ve spent any time in a biochemistry lab, you may haveexperienced the large heat given off by a salt solution as the saltdissolves. There are several contributions to the effect, but the mainone is the enthalpy of hydration. This is the enthalpy change thatoccurs when an ion in vacuum is dropped into a sea of pure water.Water molecules form what is called a hydration shell around theion, the number depending on the radius of the ion and its charge.Calorimetry can be used to measure the hydration enthalpy of bio-logically important ions. Values are given in Table 2.5. Why is thisimportant? In one example, some of the water molecules hydratingan ion must be stripped away before the ion can pass through aselective ion channel in the plasma membrane, and this requires aninput of energy. Complete dehydration of the ion would require avery large input of energy, so it is easy to imagine that a few watermolecules remain associated with an ion as it passes through a pore.Ion channels that are specific for the passage of certain types of ionare part of the molecular machinery underlying the transmission ofnerve impulses.
Fig. 2.8 Isothermal titration
calorimeter. The temperature is
constant. There are two identical
chambers, the sample cell and the
reference cell. In most cases, the
sample cell will contain a
macromolecule, and the syringe/
stirrer is used to inject a ligand into
the sample cell. The syringe is
usually coupled to an injector
system under software control and
rotated at a constant speed. The
reference cell is filled with buffer;
no reaction occurs there. 1Tmeasures the temperature
difference between cells, which are
surrounded by insulation to
minimize heat exchange with the
surroundings. Electronic (power
feedback) circuitry minimizes 1T
on a continuous basis. If injection of
ligand results in binding, there will
ordinarily be a change in the
temperature of the sample. The
sign of the change will depend on
whether the reaction is exothermic
or endothermic. An experiment
consists of equal-volume injections
from the syringe into the sample
cell.
46 THE FIRST LAW OF THERMODYNAMICS
What if we’re interested in the energetics of an enzyme bindingto its substrate? This can be measured if a suitable substrate analogcan be found or the enzyme can be modified. For instance, ITC hasbeen used to measure the enthalpy of binding of a small compoundcalled 20-cytidine monophoshate (20CMP) to ribonuclease A, whichhydrolyzes RNA to its component nucleotides. 20CMP binds to andinhibits the enzyme. If the enzyme of interest is, say, a proteinphosphatase with a nucleophilic cysteine in the active site, muta-tion of the Cys to Ser or Asn will abolish catalytic activity, as in theN-terminal domain of the cytoskeleton-associated protein tensin,and the energetics of binding can be studied. A deeper under-standing of binding will be sought in Chapters 5 and 7.
If you’ve spent any time in a biochemistry lab, you may haveexperienced the large heat given off by a salt solution as the saltdissolves. There are several contributions to the effect, but the mainone is the enthalpy of hydration. This is the enthalpy change thatoccurs when an ion in vacuum is dropped into a sea of pure water.Water molecules form what is called a hydration shell around theion, the number depending on the radius of the ion and its charge.Calorimetry can be used to measure the hydration enthalpy of bio-logically important ions. Values are given in Table 2.5. Why is thisimportant? In one example, some of the water molecules hydratingan ion must be stripped away before the ion can pass through aselective ion channel in the plasma membrane, and this requires aninput of energy. Complete dehydration of the ion would require avery large input of energy, so it is easy to imagine that a few watermolecules remain associated with an ion as it passes through a pore.Ion channels that are specific for the passage of certain types of ionare part of the molecular machinery underlying the transmission ofnerve impulses.
Fig. 2.8 Isothermal titration
calorimeter. The temperature is
constant. There are two identical
chambers, the sample cell and the
reference cell. In most cases, the
sample cell will contain a
macromolecule, and the syringe/
stirrer is used to inject a ligand into
the sample cell. The syringe is
usually coupled to an injector
system under software control and
rotated at a constant speed. The
reference cell is filled with buffer;
no reaction occurs there. 1Tmeasures the temperature
difference between cells, which are
surrounded by insulation to
minimize heat exchange with the
surroundings. Electronic (power
feedback) circuitry minimizes 1T
on a continuous basis. If injection of
ligand results in binding, there will
ordinarily be a change in the
temperature of the sample. The
sign of the change will depend on
whether the reaction is exothermic
or endothermic. An experiment
consists of equal-volume injections
from the syringe into the sample
cell.
46 THE FIRST LAW OF THERMODYNAMICS
sábado, 5 de outubro de 13
Box 2.2. Cont.
micromachined nanocalorimeter which functions as a biosensor. A small number
of living cells are present in a sub-nanoliter chamber. The small size of the
chamber could be useful for rapid screening of small samples. The sensor
comprises a 10-junction gold and nickel thermopile on a silicon chip. A thermopile
is a number of thermocouples, 10 in this case, connected end on end, and a
thermocouple is simply a temperature-measuring device consisting of two wires of
different metals fused at each end. A temperature difference between the metals
results in a difference in an electrical potential, which can be calibrated to a
temperature. The nanocalorimeter of the Glasgow group can detect a mere
13 nW of power generated by the cells on exposure to a chemical stimulus, the
temperature resolution is 0.125mK, the heat capacity is 1.2 nJ mK!1, and the
response time is 12ms. Primary cell lines or tissue biopsies can be analyzed.
Fig. 2.10 Differential scanning
calorimetry. (A) Schematic diagram
of the instrument. In
this case the reference cell contains
buffer only, and the sample cell
contains the macromolecule
dissolved in buffer. Both cells are
heated very slowly (e.g. 1 "C min!1)
in order to maintain equilibrium,
and feedback electronic circuitry is
used to add heat so that 1T # 0
throughout the experiment. Other
types of DSC have been used for
other purposes in biophysics, for
example, to investigate the
physiological limits of the freeze
tolerance and freeze-avoidance
strategies taken by different insect
species to survive subzero
temperatures. (B) Data. The heat
added to keep 1T # 0 can be
plotted as a function of
temperature. The endothermic
peak corresponds to heat absorbed,
for example, on protein
denaturation. The peak maximum
corresponds roughly to the
transition temperature, or melting
temperature. The area below the
peak is 1Hd(Tm). The heat capacity
of the unfolded state of a protein
minus the heat capacity of the
folded state is 1Cp,d. There is more
about DSC in Chapter 5.
50 THE FIRST LAW OF THERMODYNAMICS
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H. Heat capacity
Above we noted that the heat taken up or released per unit changein temperature from a material at constant pressure is a property ofthat material. The name of this property is the heat capacity atconstant pressure, Cp.
13 This quantity is readily measured, and it canbe used to calculate changes in the enthalpy. The heat capacity perunit mass of Coke, for example, which is mostly water, differs fromthe heat capacity per unit mass of an egg, which contains a largeamount of protein; the amount of heat energy that must beextracted from 1g of each in order to lower the temperature by1 degree K will not be the same in the two cases. The heat capacitytells us how much energy is in the system for transfer between itselfand the environment per degree.
It is evident from Fig. 2.7 that the enthalpy of a protein rises asits temperature is increased. This is true of substances in general.The numerical relationship between H and T, however, depends onthe conditions. We concern ourselves here with constant pressureonly. The slope of a graph of H versus T at constant pressure is theheat capacity at constant pressure.
We are all familiar with heat capacity, even in the absence of aformal introduction. Returning to our water-in-a-saucepan example,if the water is heated at a high enough rate, it will eventually boil.The amount of heat that must be added to increase the temperatureof 1 g of a substance by 1 degree K is the specific heat capacity. At 1 atmpressure, the heat capacity of liquid water varies only very slightlywith temperature over the range 0–100 !C. This comes from thebonding structure of water (Fig. 2.9). Just as the extent of motionchanges substantially when a quantity of water freezes or vaporizes,the heat capacity of water depends substantially on its state. This istrue of substances in general. But the number of hydrogen bonds
Table 2.5. Standard ion hydration enthalpies
H" #1090 Mg2" #1920Li" #520 Ca2" #1650Na" #405 Ba2" #1360K" #321 Fe2" #1950— — Zn2" #2050NH4" #301 Fe3" #4430
The data refer to X"(g)!X"(aq) at 1 bar and are from Table 2.6c in Atkins (1998). 1 bar$ 105
Pa$ 105 N m#2$ 0.987 atm. 1 Pa$ 1 pascal. Blaise Pascal (1623–1662) was a French scientistand religious philosopher.
13 The heat capacity per unit mass of material, or specific heat, was firstdescribed in detail by Joseph Black.
HEAT CAPACITY 47Hidratação e desidratação iônica ocorre
constantemente nos canais/bombas de íons e na transmissão de impulsos nervosos.
sábado, 5 de outubro de 13
EnergiasEnergias mais relevantes para
sistemas biológicos:1. Energia Química2. Energia Mecânica3. Energia Eletromagnética4. Energia Térmica Fotossíntese
Energias mais relevantes para sistemas biológicos:
1. Energia Química2. Energia Mecânica3. Energia Eletromagnética4. Energia Térmica
sábado, 5 de outubro de 13
EnergiasEnergias mais relevantes para
sistemas biológicos:1. Energia Química2. Energia Mecânica3. Energia Eletromagnética4. Energia Térmica
Forcas no interior da célula
Deterministicas Térmicas
Movimento Browniano
A razão entre a escalas derteminísticas e termicas é:
Edet/kBT
sábado, 5 de outubro de 13
A razão entre a escalas derteminísticas e termicas é:
Edet/kBT
kBT = 4.1 pNnm
= 0.6 kcal/mol
= 2.5 kJ/mol
= 25meV
grees of freedom is to consider collective excitations. Forexample, phonons characterize the vibrations of a crys-talline solid and magnons describe collective excitations ofmagnetic spins.
Indeed, physicists talk of “-ons” of all kinds. The bio-logical setting provides a loose analogy because somebiological structures are characterized with the label “-somes,” which derives from the Greek word for “body.”The term refers to macromolecular assemblies that aremade from multiple molecular components that act in acollective fashion to perform multiple functions. Some ofthe most notable examples include the ribosome, used inprotein synthesis; the nucleosome, which is the individualpacking unit for eukaryotic DNA; the proteasome, an as-sembly that mediates protein degradation; and the tran-scriptisome, which mediates gene transcription. By mech-anisms and principles that are still largely unknown,proteins assemble into -somes, perform a task, and thendisassemble again.
One of the most pleasing examples of biological col-lective action is revealed by the machines of the so-calledcentral dogma. The term refers to the set of processeswhereby DNA is copied (replication), genes are read andturned into messenger RNA (transcription), and finally,messenger RNA is turned into the corresponding proteinby ribosomes (translation). Such processes involve multi-ple layers of orchestration that range from the assemblyof macromolecular complexes to the simultaneous actionof multiple machines to the collective manner in whichcells may undertake the processes. Figure 3 shows the ma-chines of the central dogma in bacteria engaged in theprocesses of transcription and translation simultaneously.
The theme of collective action is also revealed in theflow of information in biological systems. For example, theprecise spatial and temporal orchestration of events that oc-curs as an egg differentiates into an embryo requires thatinformation be managed in processes called signal trans-duction. Biological signal transduction is often broadly pre-sented as a series of cartoons: Various proteins signal by in-teracting with each other via often poorly understoodmeans. That leads to a very simple representation: a net-work of blobs sticking or pointing to other blobs. Despite lim-ited knowledge, it should be possible to develop formal the-ories for understanding such processes. Indeed, the generalanalysis of biological networks—systems biology—is nowgenerating great excitement in the biology community.
Information flow in the central dogma is likewise oftenpresented as a cartoon: a series of directed arrows show-ing that information moves from DNA to RNA to proteins,and from DNA to DNA. But information also flows fromproteins to DNA because proteins regulate the expressionof genes by binding to DNA in various ways. Though all bi-ologists know that interesting feature of information flow,central-dogma cartoons continue to omit the arrow thatcloses the loop. That omission is central to the differencebetween a formal theory and a cartoon. A closed loop in aformal theory would admit the possibility of feedback andcomplicated dynamics, both of which are an essential partof the biological information management implemented bythe collective action of genes, RNA, and proteins.
Understanding collective effects in the cell will requiremerging two philosophical viewpoints. The first is that lifeis like a computer program: An infrastructure of machinescarries out arbitrary instructions that are encoded into DNA
www.physicstoday.org May 2006 Physics Today 41
Electrostatic energyof a spherical shell
Binding energy of anelectron in a box
Bending ofa 20:1 rod
Chemicalbonds
Fracture ofa 20:1 rod
Proton
Nucleus
Thermal energy
10010 310 610 910 1210 15
10 30
10 25
10 20
10 15
10 10
1010
105
10 5
100
LENGTH (meters)
EN
ER
GY
(jou
les)
Figure 2. The confluence of energy scales is illustrated in this graph, which shows how thermal, chemical, mechanical, andelectrostatic energies associated with an object scale with size. As the characteristic object size approaches that at which mo-lecular machines operate (shaded), all the energies converge. The horizontal line shows the thermal energy scale kT which, ofcourse, does not depend on an object’s size. We estimate binding energy (purple) by considering an electron in a box; for com-parison, the graph shows measured binding energies for hydrogen bonds (square), phosphate groups in ATP (triangle), and co-valent bonds (circle), along with characteristic energies for nuclear and subatomic particles. In estimating the bending energy(blue), we took an elastic rod with an aspect ratio of 20:1 bent into a semicircular arc, and to compute the fracture energy(green) we estimated the energy in chemical bonds in a longitudinal cross section of the rod. The electrostatic energy (orange)was obtained for a spherical protein with singly charged amino acids of specified size distributed on the surface.
Maquinaria molecular: Ligação de Hidrogênio (quadrado), grupos de fosfato em ATP (triângulo), ligações covalentes (círculo), energia de torção (azul), energia de fratura (verde), energia eletrostática (laranja). [Rob Phillips and Stephen R. Quake, Physics Today (2006)]
sábado, 5 de outubro de 13
Geração de Energias (Glicolise)
0
-20
-40
-60
-80
P PA
AP P P
!G' (kJ · mol-1)
P PA
AP P P
P PA
AP P P
P PA A
P P P
8
76
5
4
9
1
10
3
2
P PAA
P P P P PAA
P P P
P PAA
P P P
P PA A
P P P
1 32
8 7
4
5
22
22
N AN A
6
1
2
3
4
510
9
7
9
P
P
P
P
P
P
10
P P
6
8
2 H2O
P PA A
P P P
N A N A
P
2
2
2
2
2
!GOI = –35 kJ · mol–1
2 2
P
PP P
O
HO
OH
OH
OH
HH
HH
CH2
H
HO
O
HO
OH
OH
OH
HH
HH
CH2
H
HO
O
HO
OH
OH
OH
HH
HH
CH2
H
OO
CH2O
OH H
CH2OH
OH
HH HO
OCH2O
OH H
CH2
OH
HH HO
O
HC OH
H2C
C
O
O O
HC OH
H2C
CO O
O
HC O
H2C
CO O
OH
HC OH
H2C
C
O
O H
C O
CH2
H2C
O
OH
C O
CH2
CO O
C O
CH3
CO O
C O
CH3
COO
C O
CH3
COO
P
Pyruvate
Steps 1, 3 and 10are bypassed ingluconeogenesis
Glyceraldehyde3-phosphate
1,3-Bisphospho-glycerate
3-Phospho-glycerate
Phospho-enolpyruvate
2-Phospho-glycerate
Glycerone3-phosphate
Fructose6-phosphate
Glucose6-phosphate
Fructose1,6-bisphosphate
2 2 2
2
Hexokinase 2.7.1.1
Glucose 6-phosphateIsomerase 5.3.1.9
6-Phosphofructo-kinase 2.7.1.11
Fructose bisphosphatealdolase 4.1.2.13
Triose-phosphateisomerase 5.3.1.1 Pyruvate kinase
2.7.1.40
Phosphopyruvatehydratase 4.2.1.11
Phosphoglyceratekinase 2.7.2.3
Glucose
Pyruvate2
Glyceraldehyde-3- dehydro-genase 1.2.1.12
Phosphoglyceratemutase 5.4.2.1
Glucose Pyruvate Pyruvate
Glycolysis
A. Glycolysis: balance
C. Energy profile
B. Reactions
2
151Carbohydrate Metabolism
All rights reserved. Usage subject to terms and conditions of license.Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
0
-20
-40
-60
-80
P PA
AP P P
!G' (kJ · mol-1)
P PA
AP P P
P PA
AP P P
P PA A
P P P
8
76
5
4
9
1
10
3
2
P PAA
P P P P PAA
P P P
P PAA
P P P
P PA A
P P P
1 32
8 7
4
5
22
22
N AN A
6
1
2
3
4
510
9
7
9
P
P
P
P
P
P
10
P P
6
8
2 H2O
P PA A
P P P
N A N A
P
2
2
2
2
2
!GOI = –35 kJ · mol–1
2 2
P
PP P
O
HO
OH
OH
OH
HH
HH
CH2
H
HO
O
HO
OH
OH
OH
HH
HH
CH2
H
HO
O
HO
OH
OH
OH
HH
HH
CH2
H
OO
CH2O
OH H
CH2OH
OH
HH HO
OCH2O
OH H
CH2
OH
HH HO
O
HC OH
H2C
C
O
O O
HC OH
H2C
CO O
O
HC O
H2C
CO O
OH
HC OH
H2C
C
O
O H
C O
CH2
H2C
O
OH
C O
CH2
CO O
C O
CH3
CO O
C O
CH3
COO
C O
CH3
COO
P
Pyruvate
Steps 1, 3 and 10are bypassed ingluconeogenesis
Glyceraldehyde3-phosphate
1,3-Bisphospho-glycerate
3-Phospho-glycerate
Phospho-enolpyruvate
2-Phospho-glycerate
Glycerone3-phosphate
Fructose6-phosphate
Glucose6-phosphate
Fructose1,6-bisphosphate
2 2 2
2
Hexokinase 2.7.1.1
Glucose 6-phosphateIsomerase 5.3.1.9
6-Phosphofructo-kinase 2.7.1.11
Fructose bisphosphatealdolase 4.1.2.13
Triose-phosphateisomerase 5.3.1.1 Pyruvate kinase
2.7.1.40
Phosphopyruvatehydratase 4.2.1.11
Phosphoglyceratekinase 2.7.2.3
Glucose
Pyruvate2
Glyceraldehyde-3- dehydro-genase 1.2.1.12
Phosphoglyceratemutase 5.4.2.1
Glucose Pyruvate Pyruvate
Glycolysis
A. Glycolysis: balance
C. Energy profile
B. Reactions
2
151Carbohydrate Metabolism
All rights reserved. Usage subject to terms and conditions of license.Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
Pyruvate possui grande valor
energético e pode ser utilizado para produzir mais ATP.
Assim, uma molécula de glicose pode gerar até 30
ATPs.
sábado, 5 de outubro de 13
Geração de Energias
sábado, 5 de outubro de 13
Armazenamento de Energias
ATP
ADP
Pi
ATP +H2O ! ADP + Pi
� 30.5 > �Go > �50 kJ/mol
kBT = 4.1 pNnm
= 0.6 kcal/mol
= 2.5 kJ/mol
= 25meV
C � C ! 346 kJ/mol
C = C ! 602
C �H ! 415
H �H ! 436
O = O ! 498
sábado, 5 de outubro de 13
-10
-20
-30
!G OI
kJ · mol-1
" #$Mg
P PA
AP P P
P
ATP
H
P PA
AP P PP
P
P
e
N
CHN
C
CC
NHC
N
NH2
OCH2O
H
OH OH
HH H
P
O
O
OPO
O
O
P
O
O
O
#"$
P
P
P
P
+
4
ATP
P
P
P
Aden
osin
e+
3
AMP
P
P
ATP
+
2
ADP
ATP
P
+
1
321
A
H
OCH2O
H
OH
H
P
O
O
OPO
O
O
#"
A. ATP: structure
C. Types of ATP formation
2. Mg2 -Complex
B. Hydrolysis energies
Phosphorylatedsubstrate
Enzyme
Substrate
1. Phosphate transfer
Electrons
Protons ATPsynthase
ADP
2. Oxidative phosphorylation
Phosphoric acidanhydride bonds
Phosphoric acidester bond
Aden
ine
1. Formula
2. ATP: charge density
ATP
Substratechain phos-phorylation
N-glycosidicbond
Positive
Neutral
Negative
1. Hydrolysis energies
Ared
AdenosinePhosphate residue
Ribose
ADP
123Energy Metabolism
All rights reserved. Usage subject to terms and conditions of license.Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005
sábado, 5 de outubro de 13
ATP-ADP ~ varias tipos de reações bioquímicasATP-ADP ~ 20 kBT
Ligação covalente típica ~ 150 kBT
NADP+
sábado, 5 de outubro de 13