GENERAL OVERVIEW:

1: Glucose:

a: Food, what keeps you going... the energy that keeps you alive. [true for all organisms] b: one of the true beauties of Biochemistry is:

✦ when we talk about the diversity of life, when we start studying the enzymes, proteins, metabolic pathways... they are all the same.

• At the biochemical level, we are all on an equal playing field • All anaerobic organisms [those that live on oxygen] oxidize glucose to carbon dioxide and water.

• Huge heat releasing rxn. • the enthalpy of rxn. is very, very favorable. • that heat, is basically dissipated into the outside world→ and goes to waste

TUESDAY 01-07-14

• The trick of metabolism, is to capture that energy to do something useful with it.

• Takes energy to make DNA, proteins

• To not waste energy as heat, what nature has done is devised a way to break down glucose in a bunch of little steps

• each step releases a little bit of energy, and so what the cell does, it captures that energy in little packets and stores it as ATP. [Taking heat energy and converting it to chemical energy]

Do this in incremental steps it what allows the cell to capture the heat energy.

2: The whole science of thermodynamics, and Physical chemistry is:

a: If you take any kind of energy yielding rxn. and you take out the energy in little bitty pieces...

✦ You get much more efficiency, then you would by trying to capture the heat at the end. [ It's impossible to capture all the heat and chemical energy at the end of the rxn. → but you capture a lot more if you do it in little tiny packets]

3: Equate H atoms w/ Energy.

a: the more H atoms a molecule has, the more energy rich it

is. b: Therefore glucose is a very energy rich molecule [ b/c it has a lot of H atoms]

✦ if you rip off all H atoms and give to Oxygen → very favorable rxn.

3: The Rxn. of molecular oxygen ( ) of any biological molecule (amino acids, glucose, DNA, etc) is a very favorable rxn. [IT LIES TO THE RIGHT]

a: Oxygen is a very powerful oxidizing agent, and what it wants to do is take H atoms away from molecules b: THINK ABOUT THIS:

We are made up of a whole bunch of H atoms within our molecules, and we live in a atmosphere of about 20% oxygen; how is that possible that we don't spontaneously ignite. Why arn't we burning up?

4: Where does the glucose come from?

a: We want to run the rxn. backwards... want to add H atoms to Carbon Dioxide to make glucose [ takes a lot of energy to

do] b: Where does the energy come from?

THE SUN → PHOTOSYNTHESIS [the source of energy on earth]

• enables plants to take carbon dioxide and combines it with H atoms to make glucose

• we eat plants, animals eat plants, we eat animals → how we get glucose.

THE SOURCE OF ALL ENERGY IS THE SUN

5: We know that Entropy is associated with order and disorder, so things tend to spontaneously disorder. That's what's happening on earth → this balance of order and disorder.

HOW IS IT POSSIBLE THAT WE KEEP ON DECREASING ENTROPY IN THE BIOSPHERE (EVERYTHING BECOMES MORE ORDERED), WHEN THE 2ND LAW OF THERMODYNAMICS TELLS US THAT EVERYTHING MUST SPONTANEOUSLY DISORDER??

The earth and everything around it has been looked at as a "closed system" that is we have the earth, atmosphere, and we are not exchanging energy with anything else out there.

If you have a closed system → has to spontaneously disorder [ can't cause things to be ordered, unless there is energy coming from the outside forcing things to become ordered]

Where is that energy coming from?

The earth is not a closed system, we are an open system. We are exchanging with the universe, so what is providing us with that energy to order things around us?

THE SUN when to sun goes, we become a closed system and we all go bye bye.

WHAT'S UNIQUE ABOUT BIOCHEMISTRY, COMPARED TO OTHER CHEMISTRY CLASSES?

1: Working at room temperature, 37 °C

2: Operating at neutral pH (life is not compatible outside of a very narrow pH range)

A: Kinds of Molecules we are concerned with:

1: Macromolecules (big molecules)

a: Polysaccharides - energy storage

• sugar unit that repeats itself over and over again. • what starch, cellulose look like

b: Nucleic acids - genetic info.

c: Proteins - enzymes, structural

[What they all have in common, when they form a bond, water is eliminated from the molecule in the process]

• More efficient to store a polymer than each individual units due to less Os and Hs in the polymer compared to each individual units which have more Os and Hs that take up space.

B: All of this is happening in water. (water - unusual properties)

C: Weak forces (really prevalent in biochemical systems)

1: What is the difference between a weak and a strong force?

• a covalent bond between 2 atoms is a really strong force. • Weak forces are non-bonding interactions that are not covalent

2: Key factor that controls protein folding

3: How the double helix is formed

3 KEY CONCEPTS THAT REALLY SEPARATE BIOCHEMICAL SYSTEMS FROM ORGANIC CHEMICAL SYSTEMS.

BIOENERGETICS, THERMODYNAMICS

A: EQUILIBRIUM CONSTANT:

Example:

2: If rxn. is favorable K > 1.0 (if a process is spontaneous, then rxn. is moving to the right)

3: If rxn. is not favorable K < 1.0 4: RULE OF THUMB: What you find in biological systems, a protein and an enzyme bind together → K for that kind of rxn. is in the order of roughly [ biology operates in equilibrium

constants in that range] WE USUALLY DON'T TALK IN TERMS OF EQUILIBRIUM CONSTANTS, WE INSTEAD TALK IN TERMS OF FREE ENERGY.

B: FREE ENERGY (G):

1: Another measurement of spontaneity of a rxn. 2: We can not normally measure the free energy of the reactant or the product, but we can measure the change in free energy as we go from reactants to products.

a: So if a rxn. is spontaneous:

3: What you don't want to mix up is free energy with things like potential energy.

a: example - have a positive charge and a negative charge, there's an energy of interaction between the two [NOT FREE ENERGY CHANGE]

The free energy change is the measure of whether it wants to be in one state vs. another.

Its the measure of the equilibrium constant, how far to the left or right does the rxn. sit.

C: Relationship between K (equilibrium constant) and ỎG (free energy)

1:

2: ỎG = Standard state free energy

[rm temp, 1atm pressure, pH 6] **not going to go away from this in this class. will always be standard state free energy**

a: Basically tells us if, at equilibrium, a reaction lies to the right or left.

3: ỎG = Free energy under non-equilibrium conditions

a: inside living systems reactions, quite often operations in biology

b: ỎG ≠ 0

4: therefore... 5: Example:

a: Suppose we have 1mM Fructose-6-phosphate and 5mM Glucose-6-phosphate. What is the free energy change?

D: you can couple unfavorable rxn. with favorable rxn. [Free energies are additive]

1: This is how we drive rxns. that are unfavorable 2: example

Key rxn. to get glucose into metabolism, is to phosphorylate

• Stick phosphate group on glucose, gets it ready for further metabolism.

3: An enzyme can make a rxn. go faster, but it cant change ỎG.

a: You can make rxn. go faster, but you cant change the thermodynamics. [THE THERMODYNAMICS IS ABSOLUTE]

4: What nature has done is devised a way to couple these rxn.

a: So we are using the favorable rxn. of ATP hydrolysis and coupling it with with the phosphorylation of Glucose to drive the rxn.

✦ So what the enzyme does is binds glucose and binds ATP puts them together and the rxn. can go at the active site. [in soln. nothing happens].

• the thermodynamics hasn't changed, it is the enzyme that allows the rxn. to happen. THIS IS HOW BIOCHEMICAL RXNS. ARE PUSHED.

E: ENTHALPY & ENTROPY:

1: The free energy (ỎG) is not alone, it is defined by enthalpy (ỎH) & Entrophy (ỎS).

ỎG = ỎH - T ỎS

a: What this tells us is ỎH is negative → rxn. is favorable b/c ỎG will be more negative.

b: If ỎS is positive → rxn. is more favorable b/c we have a minus a positive c: If ỎS is negative → rxn. is an unfavorable process b/c a minus times a minus become a positive.

2: ENTHALPY (ỎH): is the heat given off in a rxn. ỎH = H - H

a: example:

You have water and drop HCl into the water, the beaker gets hot.

• ỎH for the rxn is <0 (its negative) • if the heat of the rxn. is negative, then the change in heat of the rxn. is negative. WHY DID THE BEAKER GET HOT??

The beaker is not part of the rxn. it is just holding the rxn. In thermodynamics everything is about the system. What defines the system. → In this case the system is water & HCl. The beaker doesn't count, it is just the carrier. THEREFORE...

The beaker got hot, what that means is the rxn. got cool. meaning it gave off heat & the heat had to go somewhere→ went to the outside world meaning the beaker.

b: Example 2:

Lets say we take urea (which is really soluble) and dump it in water, the beaker gets really cold. It will start to condense leading to little drippings on the side of the beaker.

Is ỎH positive or negative for that rxn?

ỎH > 0 [ positive]

b/c the beaker got cold, the beaker was giving heat to the rxn.

SO DON'T BE FOOLED BY WHAT THE RXN. FEELS LIKE B/C IT IS NOT PART OF THE SYSTEM. THE SYSTEM ITSELF WHICH IS ACTUALLY UNDER GOING THROUGH RXN. IS CHANGING THE OUTSIDE WORLD. c: IN GENERAL:

• The making of bonds, is a favorable ỎH. [ỎH < 0] • When you break a bond, is an unfavorable ỎH [ỎH > 0]

3: ENTROPY (ỎS):

Is a measure of order in the system. ỎS = S - S

• In the purist turn is a measure of spontaneity.

a: It turns out that things spontaneously goes from higher order to lower order (where concept of order and disorder came from) b: ỎS > 0 is always favorable

[a spontaneous/ favorable process tends toward disorder]

c: Classic example:

In order to go from disorder (large S) to order (small S), energy must be applied. → have to push down to hold molecules together.

F: Enthalpy and Entropy in terms of Molecules:

1:

✦ ỎH < 0 [making of a chemical bond is usually a heat generating process] ✦ In going from 2 molecules to 1 molecule, the system has become more ordered THEREFORE ỎS < 0 [this opposes the rxn] ✦ You don't have one dominating over the other... has to be a balanced between enthalpy and entropy. VERY TYPICAL FOR ENTHALPY AND ENTROPY TO BALCNE OR COMPENSATE FOR ONE ANOTHER.

2: Examples:

a: rxn. between oxygen and hydrogen to form water. b:

ỎG < 0 therefore favorable rxn. ỎH > 0 therefore not favorable

[reason: broken up a lot of bonds] ỎS > 0 therefore favorable

[reason: taken complex molecule, and busted it up into 2 1/2 compounds]

WEAK FORCES

1: What makes weak forces so special in biology is that everything occurs in water [water is a pretty strange molecule]

a: Water:

✦ is tetrahedral ✦ has 2 H atoms ✦ is a double headed molecule b/c it has 2 positive poles and 2 negative poles ✦ has 2 unpaired e-s ✦ can do a lot of electrostatic interactions HOW MANY HYDROGEN BONDS CAN A SINGLE WATER MOLECULE FORM?

4 bonds

✦ has a strong dipole moment

• The longer the vector, the stronger the dipole... that means the stronger the charge separation on the molecule.

2: DIPOLE MOMENT: The ability of the molecule to reorient itself among another molecule.

a: Other dipole example:

b: Most organic molecules don't have a dipole

ex: methane, ethane, benzene. ✦ don't have a fixed dipole, they don't have a charge separation

• however, take 2 benzene and bring them together, the e-s in that molecule will want to redistribute (reorient) themselves so that the positive end of one benzene is next to the negative end of the other

[the e-s in one benzene molecule will slightly redistribute themselves so there will be a negative end, a positive end, and the one next to it will have the same distribution but

flipped around ANTIPARALLEL. ]

• Benzene molecule all by itself has no dipole, but put it next to another organic molecule, the e-s rearrange themselves to give an INDUCED DIPOLE

REALLY IMPORTANT IN BIOLOGY B/C THIS IS HOW NON POLAR UNCHARGED MOLECULES INTERACT WITH ONE ANOTHER.

c: Induced dipole has a special formulation

✦ 2 types of real energy

"Whats the energy of 2 atoms interacting with each other?" • Have 2 molecules that are infinity apart, and start to bring them together... there is going to be an attraction between the 2

- dipoles are going to start inducing - molecules are going to flip around and light up - distance at which everything is absolutely perfect and everything is optimal. [NEGATIVE ENERGY IS FAVORABLE]

- Take the two atoms and push them even closer, the energy is going to start going positive [ repulsive term]

OPTIMAL DISTANCE = REPULSIVE + ATTRACTIVE

✦ Important in biology b/c when a substrate interacts with an enzyme a lot of them are non polar atoms that are interacting with one another, so they don't come into play until they are really close together

A: 3 Things Need to REMEMBER FOR THIS CLASS:

1: Dispersion (induced dipole)

• involves mutual synchronization of fluctuating charges

2: Charge-Charge distribution

• Longest-range force; nondirectional

• If your bring 2 molecules together, first thing your going to see is the charge difference.

opposite charges will start come together and we will get induced dipoles, when the charges come together quite a bit closer, we get charge- charge distribution.

3: Hydrogen Bond

• Charge attraction + partial covalent bond

• Special charge-charge interactions → It is directional. \

a: The special thing about water, it can form 4 hydrogen bonds.

• Can interact with itself in multiple ways.

- water molecule keeps flipping around and changing partners.

Doesn't just sit there... b/c it can do 4 H bonds, it is always bonded to another one. [Entropy is great... since it can flip around, things are relatively disordered.. by maintaining all the H bonds, enthalpy is really favorable]

b: Different functional groups that do hydrogen bonding that will be seen over and over again.

c: Though experiment:

What happens when you dissolve sodium chloride (NaCl) in water?

• It dissolves in water, why is it so soluble?

We have little water molecules with great dipoles, so Hydrogen orient themselves around the negative chlorides, where as the lone pairs on the oxygen can orient themselves around the positive sodium. BUT... AT WHAT COST? Sodium Chloride form very tight interactions, so we have to break up the +- interaction in order to get the water molecules around them [breaking up this interaction is a very unfavorable enthalpy thing to do ỎH > 0] HOWEVER WHEN WATER FORMS AROUND THE ATOMS ỎH < 0

• So why is NaCl so soluble? why does it want to break up? Driving force?

ENTROPY is the driving force. Taking highly ordered crystal lattice of salt, and breaking it up. [causing atoms to become more free... we are creating a more disordered system.]

How does this translate into proteins?

If you take two substates, and each has a charged group, and put them on active site of a protein that hydrophobic (nonpolar)... Those charge-charge interactions are going to be really strong b/c there is no water molecules to compete with it

• This is why H bonds, why charge-charge interactions all balance out.