**Introduction:**- Schröedinger:
*"The ability to decrease entropy is the MOST characteristic feature of living systems*." - Decrease in entropy means an increase in order (a state of low probability).
- Further, order may create information. Maximum entropy: scrambled letters of quote; ordered letters in quote = information.

- Schröedinger:
**Energy flow through a system orders that system**:- Energy flow from the sun has ordered the earth.
- Energy flow through biological systems: The means for creating the order seen in living cells.

**Thermodynamics and Kinetics (do not confuse these terms)****Thermodynamics**relates to*spontaneity*or "will it happen?"**Kinetics**relates to*reaction rate*or "how fast will it happen?"

**Energy**for A ® B*vs.*Reaction coordinate plot- showing
**E**; average energy of A and B; and the_{act}*thermodynamic difference*,*G*. - E
_{act}is the**kinetic**term;*G*is the**thermodynamic**term. - Considering a Boltzmann energy distribution plot illustrates the differences between these values.
- Real example of a reaction:
- C
_{6}H_{12}O_{6}+ 6 O_{2}® 6 CO_{2}+ 6 H_{2}O *G°*= -686,000 cal/mol*G°*= -2,870,000 Joules/mol (1 cal. = 4.284 Joules)- But glucose is very stable in aqueous solution in the presence of air due to a high energy of activation.

- C

- showing
**Consider**:- A ® B + energy
*G*=*G*_{B}-*G*_{A}(*G*_{products}-*G*_{reactants})*G*is negative for spontaneous processes- if
*G*_{A}>*G*_{B},*G*is negative

**What is***G*?- It is the
- In a chemical reaction, the change in free energy (
*G*) is equal to the change in*enthalpy*(*H*) minus the absolute temperature (*T*) times the change in*entropy*(*S*):*G*=*H*-*T**S* *G*= that part of the total energy change in a process that is available to do useful work*H*= heat of reaction, the change in enthalpy (*heat content*). In dilute aqueous solutions (which cells approximate),*H*=*E*, where*E*= the change in the*internal energy of the molecules*(*E*_{B}-*E*_{A})*T**S*= that part of the internal energy change that is dissipated in the form of increased random molecular motion and hence__unavailable to do useful work__. Simplistically,*E*=*G*+*T**S*- So,
*G*= change in internal energy corrected for the change in entropy, where entropy changes are energy losses that cannot be used to do useful work. *G*tells us how much energy is available to do useful work.- Now, the
*standard-state*free energy change for a reaction (defined as the free energy change when both products and reactants are present at 1*Molar*concentrations) isD

*G°*= -*RT*ln*K*_{eq}where

*K*= [B]_{eq}_{eq}/[A]_{eq}If

*K*is small, D_{eq}*G*is positiveIf

*K*is large, D_{eq}*G*is negative **D***G*is just another way of writing an equilibrium constant for a reaction.

__change__in free energy in a reaction.- In a chemical reaction, the change in free energy (
**A Cell Does 3 Kinds of Work***Mechanical work*: muscle contraction; axonal transport; cytoplasmic streaming*Transport work*: the pumping of substances against concentration gradients,*e.g.*, the Na^{+},K^{+}pump (Na^{+},K^{+}-ATPase)*Chemical work*: driving reactions that are not spontaneous (reactions that have a +D*G*, such as do all dehydration synthesis reactions)

**In most cases, ATP is the source of energy for cellular work**.- ATP hydrolysis releases lots of energy:
- ATP + H
_{2}O _ ADP + P_{i}+ energy released - D
*G°*= -7,300 calories/mol = -7.3 kcal/mol = -30.5 kJ/mol - D
*G*_{cellular}» -12,000 calories/mol = -12 kcal/mol = -50 kJ/mol - Of course, ATP synthesis "costs" a lot of energy (+50 kJ/mol in the cell).

**How ATP Works**- Consider a reaction, A ® B, where D
*G°*= +4 kcal/mol- D
*G°*= +4,000 cal/mol = -*RT*ln*K*_{eq} - D
*G°*= -(1.987 cal/° mol)(310K)ln*K*_{eq} - ln
*K*= -6.49_{eq} *K*= 0.0015 = [B]_{eq}/[A]_{eq}very little B at equilibrium!_{eq}

- D
- Now consider the
*coupled reaction*,- A + ATP + H
_{2}O ® B + ADP + P_{i} - Since for A ® B, D
*G°*= +4 kcal/mol, - and for ATP + H
_{2}O ® ADP + P_{i}, D*G°*= -7.3 kcal/mol, - D
*G°*_{overall}= -3.3 kcal/mol - Therefore, -3,300 cal/mol = -
*RT*ln*K*for the coupled reaction._{eq} - ln
*K*= 5.36 ;_{eq}*K*= 212_{eq} - Note that
*K*= ([B]_{eq}[ADP][P_{eq}_{i}])/([A][ATP]_{eq}(by convention, the concentration of the solvent, [H

_{2}O] º 1 in these thermodynamic calculations)

- A + ATP + H
- We can substitute here a typical value for the ratio of
[ATP]/[ADP][P
_{i}] in a living cell.- (ATP]/[ADP][P
_{i}])» 500_{in vivo} *K*= 212 = [B]_{eq}/500[A]_{eq}_{eq}- [B]
/[A]_{eq}= 106,000_{eq} - Now compare the ratio [B]
/[A]_{eq}in the presence_{eq}*versus*in the absence of ATP:106,000/0.0015 = 7 x 10

^{7}

- (ATP]/[ADP][P
**General Principle**:**Coupling of ATP hydrolysis to A ® B raises the equilibrium ratio of [B]/[A] by a factor of almost 10**(almost 100 million fold).^{8}-fold- Note that A ® B is generally defined: It could
be
- a chemical reaction
- mechanical work
- transport of a substance against its concentration gradient
- Anything!

- Consider a reaction, A ® B, where D
**Why is ATP "Energy-Rich"?**Or, in other words, why is D*G°*a large negative number?- In simple terms, ATP bears a
lot of negative charge (ATP
^{4-}in solution). ATP is characterized by a lot of internal electrostatic repulsion; this repulsion is relieved upon hydrolysis. Or viewed another way, ATP hydrolysis creates 2 anions, HPO_{4}^{2-}and ADP^{3-}. To re-form ATP from ADP + P_{i}requires bringing 2 like-charged molecules together (electrostatic replusion between ADP^{3-}and HPO_{4}^{2-}must be overcome to form ATP). **[ATP]**» 10_{in vivo}*mM*» 5 g/liter- A person needs about 2,000
per day ( = 2,000 kcal/day). Note: a calorie is the heat necessary to raise 1 gram of water one degree Centrigrade. A kilocalorie or kcal is 1,000 calories. A kilocalorie is also equal to one**C**alories**C**alorie (note the capital "**C**") which is the "calorie" unit used in nutrition. - 12 kcal/mol of ATP ® 167 moles of ATP to get 2,000 kcal
- 167(495 g/mole) »
**83 kg ATP per day**(more than the weight of the average (70 kg) person). - A person has » 250-300 grams of ATP total.
- Therefore, each molecule of ATP must
*turn over*(be synthesized from ADP + P_{i}and hydrolyzed again) about 300 times a day. (If not resynthesized, all the body's ATP would be converted to ADP + P_{i}in about 5 minutes.)

- In simple terms, ATP bears a
lot of negative charge (ATP