key thermodynamics parameters used to describe a biochemical reaction

ALAIN VIEL: In the previous video, I defined

key thermodynamics parameters used to describe a biochemical reaction.

In this video, I will start to answer the following question.

What drives a biomolecule to be transformed into something else?

You'll learn more about the key role of free energy and other factors

that drive biochemical reactions.

So let's take a look at a few characteristic features

of biochemical reactions.

What does free energy have to do with biochemical reactions?

As you'll recall from the previous video and from the Gibb's equation,

the free energy is the portion of the system energy that can do work.

A system rich in free energy is unstable and will spontaneously

evolve toward a more stable state with lower free energy.

So we have spontaneous and non-spontaneous reactions.

So what is a spontaneous reaction?

Let's turn to a more concrete example than a biochemical reaction.

Imagine a container filled with compressed gas.

The system has a high free energy-- is unstable.

A lot of energy is required to maintain this compressed gas at a low entropy

and in a highly ordered state.

Upon opening the container, the gas spontaneously disposes.

The entropy of the system increases.

And based on the Gibb's equation, the free energy must decrease.

In other words, a spontaneous process is characterized

by a decrease of free energy as the system

evolves toward a more stable state.

Similarly, a spontaneous biochemical reaction,

also called an exergonic reaction, is thermodynamically favorable.

This reaction does not need any energy input.

In a spontaneous reaction, the substrate,

with a high potential energy, is converted into reaction products

with a lower potential energy.

A spontaneous biochemical reaction is characterized

by a decrease of free energy, which is-- on this diagram--

the difference between the high and the low potential energy.

The change of free energy, or delta G, is negative.

The Gibb's equation can be written in terms of free energy changes

and become delta G equals delta H minus T delta

S. Where delta G, delta H, and delta S are changes of free energy,

enthalpy, and entropy, respectively.

In a spontaneous reaction, delta G is negative,

which means that delta H is lower than T delta S. The change

in energy stored in the chemical bonds, delta H,

is less than the change in entropy adjusted for temperature.

If changes of enthalpy is negative, heat is released

and the reaction is said exothermic.

If the change of enthalpy remains positive,

the reaction consumes heat, and is said endothermic.

So now what about non-spontaneous, or endergonic, reactions?

An endergonic reaction is a reaction where the products of the reaction

are less stable-- have a higher potential energy--

than the substrates of the reaction.

In this case, the change of free energy, delta G, is positive.

Let's go back to our concrete example.

Compressing air in a container is non-spontaneous,

as the system goes from a stable to a less stable state.

As you might have experience, inflating the tires of your bicycle

requires an energy input as you compress the air into the tires.

When the change of free energy, delta G, is positive,

the reaction's products have a higher potential energy than the substrates.

Spontaneity is only one aspect of a reaction.

There are three other features that characterize biochemical reactions.

They are the equilibrium constant, the directionality of the reaction,

or the velocity of the reaction.

Later in the course, a full set of videos will be devoted to velocity.

And in this video, I'll focus on equilibrium and directionality.

What is equilibrium?

And what is an equilibrium constant?

Let's consider the interconversion of a substrate

S and a product P. At equilibrium, there is

no net change of the concentrations of S and P. The interconversion continues,

but the rates of P and S formation are the same.

It does not mean that the concentration of S at equilibrium

equals the concentration of P at equilibrium.

It means that the ratio of the concentration

of P at equilibrium over the concentration of S at equilibrium

is constant.

This ratio is called the equilibrium constant.

So what is directionality?

Most biochemical reactions are reversible

and can proceed in both directions.

For example, carbon dioxide and water can be converted to carbonic acid.

And carbonic acid and dissociate into water and CO2.

This reaction is common in our cells, where

carbonic acid is the main form of carbon dioxide transport.

In what direction does this reversible reaction proceed?

The direction is determined by the Le Chatelier principle.

This principle states that when a dynamic equilibrium

is disturbed-- for example, by a change of concentration

of one region-- the position of the equilibrium

changes to counteract the disturbance.

In other words, the reaction proceeds in the direction that brings back

the reaction toward equilibrium.

So let's take a look at our example to see how directionality is corrected.

Our graph here shows the free energy of the system versus reaction progress.

For the sake of simplicity, water is not shown in this diagram.

Moving right, the graph depicts more and more carbon dioxide

being converted to carbonic acid until an extreme is reached,

when all of the carbon dioxide has been consumed.

At equilibrium, when the lowest free energy point is reached,

the ratio between the concentration of carbonic acid and carbon dioxide

equals the equilibrium constant.

Let's zoom on the left part of the graph.

It is a point in this reaction where the concentration of carbon dioxide

is much higher than the concentration of carbon dioxide at equilibrium.

The spontaneous reaction, with a negative delta G,

is downhill, toward equilibrium.

And in these conditions, the direction of the reaction

is such that carbon dioxide is converted to carbonic acid.

Now, if we focus on another part of the graph-- on the right side--

where the concentration of carbonic acid is much higher

than the concentration of carbonic acid at equilibrium,

the spontaneous reaction is once again downhill.

But this time it proceeds in the reverse direction.

Carbonic acid is converted to carbon dioxide until equilibrium is reached.

At the lowest point of free energy, the reaction is at equilibrium.

The forward and the reverse reaction still occur,

but there is no net change in the reaction progress.

So in conclusion, if we know the equilibrium

constant for a reaction and the initial concentration of the molecules

participating to the reaction, we can predict the direction of the reaction.

SPEAKER: So Alain, what about the reactions

that are occurring in our cells?

Are they all at equilibrium?

ALAIN VIEL: Almost all cellular reactions

are prevented from reaching equilibrium due to factors

such as constant addition of new substrates,

or siphoning the products away.

Later in the course, when we study metabolic pathways,

you'll learn that many reactions are maintained near equilibrium.

While key and tightly-regulated reactions

are maintained far from equilibrium.

So as long as we are alive and functioning,

the biochemical reactions occurring in our cells are not at equilibrium.

So what is the relationship between equilibrium and free energy?

Let's take a life example.

During glycolysis, this multi-step process that breaks down glucose

into pyruvate, dihydroxyacetone phosphate, or DHAP,

is converted to glyceraldehyde 3-phosphate, or G3P.

Let's assume that we studied a reaction in a test tube.

Based on the equilibrium constant, you can

determine that at equilibrium, there is about 5%

of glyceraldehyde 3-phosphate compared to 95% of dihydroxyacetone phosphate.

For this reaction, you can calculate the change of free energy.

Under standard conditions, delta G0, using the formula delta G0 equals

minus RT natural log of the equilibrium constant, R is the gas constant,

T is a temperature expressing [INAUDIBLE].

Standard conditions are conditions that were

defined by chemists and biochemists.

Under standard conditions, the reaction proceeds at a constant temperature,

T equals 298 Kelvin, 25 degrees Celsius.

And with an initial concentration of reactants of one molar,

or 1 atmosphere, if the reactants are gases.

A simple calculation shows that under standard conditions,

delta G0 for our reaction, is positive.

Therefore, the reaction is non-spontaneous.

However, we know that this reaction occurs in cells.

How is that possible?

What determines the spontaneity of a reaction in a cell

is the actual free energy change under physiological conditions.

In our example, the actual change of free energy, delta G,

takes into account the concentration of glyceraldehyde

3-phosphate and dihydroxyacetone phosphate found cells.

Delta G is given by the formula delta G equals delta G0 plus RT natural log

of k, where k is the actual ratio of glyceraldehyde

3-phosphate and dihydroxyacetone phosphate concentrations in the cell.

A simple calculation indicates that under physiological conditions,

delta G equals minus 0.7 kilocalories per mole.

The negative delta G shows that the forward reaction,

the production of glyceraldehyde 3-phosphate, is spontaneous.

You should know that at equilibrium, there

is no net change of concentration.

And therefore, no work is done.

If no work is done, by definition, delta G equals 0.

The equation becomes 0 equals delta G0 plus RT natural log of the equilibrium

constant.

Or, delta G0 equals minus RT natural log of the equilibrium constant.

That is where the equation linking delta G0 and the equilibrium constant

comes from.

So in this video, we've discussed the progression of a reaction

toward equilibrium, the role of a free energy as the reaction's driving force.

You've also discovered that one can predict and calculate

the outcome of a reaction.

These concepts will be key to your understanding, later in the course,

of the flux of molecules through metabolic pathways.

structural diversity that is created by carbon atoms

ALAIN VIEL: In the previous video, you've

learned about the structural diversity that is created by carbon atoms.

Atomic composition is not the only factor that

determines the identity of a molecule.

Some molecules have the same atomic composition,

but have different three-dimensional structure.

In our example here, maleic and fumaric acids have the same composition,

but the double bond blocks the free rotation about the carbon-carbon axis.

Interconversion is prevented unless covalent bonds are broken.

The two molecules are said to have different configurations.

They are also called stereoisomers.

Maleic acid, with its two bulky groups, represented in purple on this diagram,

on the same side of the double bond.

And this molecule corresponds to the cis configuration.

Fumaric acid, with its two bulky groups on opposite sides of the double bond

corresponds to the trans configuration.

A double bond is not a prerequisite to have configurational isomers.

Molecules with the same composition and containing a chiral center

can also exist in different configurations.

So what is a chiral center?

It is a place in a molecule where a carbon is

bound to four distinct chemical groups.

In our example, the chiral carbon is linked to one hydrogen

and to three distinct chemical groups, R1, 2, and 3.

If the carbon was linked to one hydrogen, to the group R2,

and to two identical groups, R1, the carbon would be said achiral.

Depending on how the four groups are arranged around the chiral carbon,

different configurational isomers are found.

Once again, a switch from one configuration to another

requires the breaking of covalent bonds.

The two different configurations of a molecule containing a chiral center

are called enantiomers.

Enantiomers are mirror images of each other, as you can see on this diagram.

No matter how you rotate the original chiral molecule,

you never obtain its mirror image without breaking covalent bonds.

In contrast, you can obtain the mirror image of an achiral molecule

by simple rotation of the chemical groups.

This is a similar concept to our hands and feet.

As you can see on this diagram, our feet are mirror images of each other.

Now take a look at my hands.

If I show you the palm of my two hands, they are mirror images of each other.

My thumbs point toward each other.

I need to rotate one of my hands to have my two thumbs pointing

in the same direction.

But now you can see the palm of one of my hands,

and the back of the other hand.

I would have to cut, rearrange, and glue back some fingers

to show you the palm of my hands and have my thumbs

pointing in the same direction.

And I'm not ready to do it.

So what are the biochemical consequences of having

molecules in different configurations?

The interaction between ligands and their receptors in cells

are stereo-specific.

Molecules with the same composition but different configurations

bind to different receptors, thereby increasing functional diversity.

In our example, R- and S-Carvone are two enantiomers,

and are mirror images of each other.

They bind to distant receptors on nerve cells in your nose.

The binding of R-Carvone to its specific receptor

leads to a sensation of a fresh spearmint smell.

The binding of S-Carvone to its specific receptor

leads to the perception of a pungent caraway smell.

SPEAKER: So double bonds don't allow any rotation, but what about single bonds?

Single bonds do allow free rotation.

The different spatial arrangements of a molecule caused by free rotation

are called conformations, not to confuse with configurations.

The switch from one conformation to another

does not require the breaking of a covalent bond.

In theory, molecules can adopt an infinite number

of possible conformations.

However, some are more stable than others and become prevalent.

Take this molecule of ethane, for example,

and consider two of its conformations, shown on the graph.

These conformations result from a rotation of a methyl group, CH3,

about the carbon-carbon bond located in the center of the molecule.

The graph shows the potential energy of these two extreme conformations,

one having the hydrogen eclipsed with one another, one having the hydrogen

staggered apart.

Due do steric hindrance, the staggered conformation

has a lower potential energy.

As we'll learn in the next videos, it means

that the staggered conformation has a highest

ability than eclipsed conformation.

The free rotation gives flexibility to biomolecules,

and allows biomolecules to reach their most stable conformation.

So in these last two videos, you learned that carbon is a versatile building

block of biomolecules.

Carbon is a key element explaining both the structural and functional diversity

of biomolecules.

In the next video, we'll see a variety of ways

carbon is exchanged between living organisms and their environment.

We'll also introduce the concept of energy transfer,

another key component distinguishing living from inert matter.

What are the major atoms found in living versus inert matter?

ALAIN VIEL: In your everyday life, you are surrounded

by living organisms, non-living things.

What does make the difference between the two?

Are there special atoms, chemicals found only in living organisms?

In this video, you'll discover that inert and living matters are, in fact,

not distinguished by the chemical elements they contain

but by the relative abundance of these elements and the connection

they make with each other.

What are the major atoms found in living versus inert matter?

This periodic table shows a smaller number of elements labeled in green.

These are the major components of living organisms.

They are combined to form a large number of biomolecules that

vary both in structure and complexity.

The elements labeled in yellow are present in trace amounts in living

organisms but still have vital roles that will be discussed in later videos.

As you can see on this table, carbon, oxygen, hydrogen, nitrogen

make up 95% of the weight of a human body.

Carbon by itself represents 50% of dessicated living matter.

In contrast, in Earth's crust, carbon, hydrogen, and nitrogen

are present in low or trace amounts.

In contrast, oxygen, silicon, aluminum, and iron

are the major components of the crust.

Why is so much carbon needed in living organisms?

Aside from water, the majority of biomolecules are carbon-based.

It is efficient for living organisms to use one atom for a lot of purposes.

Its extreme versatility makes carbon a unique atom.

Carbon can be used to build molecules of different shapes

and geometry-- linear chains, branch chains, cyclical structure.

This structural diversity leads to functional diversity.

So let's take a look at a carbon atom.

Carbon has 6 protons, 6 neutrons, and 6 electrons.

The number of electrons and their position in atomic orbitals

are key to carbon's versatility.

Electrons are distributed in space with specific shapes called "orbitals."

For carbon, the first two orbitals-- each containing two electrons--

are spherical and they are called "1s" and "2s."

The 2s orbital is further away from the nucleus than the 1s.

Carbon has also three equivalent barbell-shaped orbitals

called 2px, y, and z.

The remaining two electrons are unpaired,

and each occupies one 2p orbital-- leaving

the third orbital, 2pz, unoccupied.

Remember, covalent bonds between two atoms

are formed when one orbital for each atom carrying an unpaired electron

fuse into a molecular orbital, which will now contain two electrons.

Based on my description on the carbon atom with its two unpaired electrons,

one could predict that a carbon atom can only form two covalent

bonds with other atom.

But you probably know some molecules where carbon makes four bonds.

Methane, a byproduct off the metabolism of some bacteria,

is one of such molecule where one carbon forms four bonds with hydrogen atoms--

as you can see on the three-dimensional structure.

I will take this opportunity to describe how will we represent molecules

in three dimension.

The bonds depicted by straight lines on this figure

are in the plane of the screen.

The bond, represented by a solid wedge, sticks out of the screen-- towards you.

And the bond represented by a hashed wedge

sticks backwards-- behind the screen.

How can carbon make four covalent bonds?

The electron in carbon can shift around, and one electron from the 2s orbital

can be promoted to the empty 2pz orbital.

Now, the 2s the three 2p orbitals contain each an unpaired electron.

So in theory, now four covalent bonds can

be formed, which would be unequal since unpaired electrons are not

on identical orbitals.

Unequal bonds are very unstable.

So what's the solution?

Promoting one electron is not sufficient.

The orbitals must also undergo a process called "hybridization."

The hybridization of the four orbitals equalizes the characteristics

of the four unpaired electrons.

The newly-formed sp3 orbitals have 25% S character and 75% P character.

On this diagram, we can see the four sp3 orbitals of carbon

needed to form a molecule of methane.

These orbitals spread themself into space

as far from each other as possible.

Each fuses with the S orbital of an hydrogen atom

forming four identical bond at 109.5 degree from one another.

The carbon occupy the center of a geometric shape

called a "tetrahedron" with the four hydrogens at the vertices.

Now, how can carbon make bonds with three-- and not four-- other atoms?

In biomolecules such as ethylene-- a plant hormone

controlling the ripening of fruits-- each

carbon bonds three atoms, two hydrogen and the other carbon.

In this case, electrons have to rearrange differently

around the carbon atom.

In other words, a different type of hybridization occurs.

Once again, one electron from the 2s orbital is promoted to a 2p orbital.

However, only three-- and not four-- hybrid orbitals are formed.

These are called the "sp2 orbitals," and they have 33% S character and 67% P

character.

The sp2 orbitals are arranged in a planar, trigonal structure--

120 degree apart from each other.

The remaining unpaired electron still occupies a 2p orbital.

This 2pz orbital is orthogonal to the plane containing the sp2 orbitals.

To make ethylene, two trigonal structures come together.

Two sp2 orbitals fuse head-to-head to form a sigma covalent

bond between the two carbons.

The sideways overlap of the two 2pz orbitals lead to the formation of a new

covalent bonds-- called a "pi bond"-- between the two carbons.

Each of the remaining four sp2 orbitals fuse

with the 1s orbitals of hydrogen atoms to form four carbon hydrogen bonds.

In ethylene, the two carbons are linked by a double bond-- one sigma and one pi

bond.

The electrons involved in the pi bond occupy a ring-shaped space

between the two carbons.

Finally, how can carbon bond with two other atoms?

Once again, one electron from the 2s orbital

is promoted to the empty 2p orbital, and then

two of the orbitals carrying unpaired electrons are hybridized.

The result are two sp orbitals with 50% S character and 50% P character.

The sp orbitals are 180 degrees from each the.

Other two unpaired electrons remain on 2p orbitals-- 2py and 2pz.

When two of these linear structures come together,

two sp orbitals overlap head-to-head to form

a sigma bond between the two carbons.

Sideways overlaps between pairs of 2p orbitals on each carbon

leads to the formation of two pi bonds between carbons.

Therefore, the two carbons are connected by a triple bond.

Finally, the other sp orbitals-- carried by the two carbon-- fuse

with the 1s orbitals of hydrogen atoms to form two carbon hydrogen bonds.

The molecule formed is acetylene.

Acetylene is not produced by living organisms

but can be made synthetically and used to ripen fruits.

Acetylene is extremely combustible due to the instability of the triple bonds.

This instability might explain why almost no biomolecule

contain a triple bond.

So now, what are the consequences of the various types of bonds

found in biomolecules?

Different bonds affect the geometry and the reactivity of biomolecules.

As you can see on this table, we can consider three characteristics.

First, we will consider the differences in bond length.

The shape of a molecule is determined by the type of atom's bond.

For example, a bond between an oxygen and a nitrogen

is shorter than a single bond between two carbons.

The shape of the molecule is also determined by the presence

of a single versus a double bond.

As you can see on the table, the length of a double bond between two carbons

is shorter than the length of a single bond between two carbons.

The second characteristic to take into account is the strength of the bond.

Different bonds have different strengths.

For example, the bond strengths between carbon linked by a double bond

is higher, as you might expect, than that of carbon linked by a single bond

but not twice as high.

Therefore, the pi bond is weaker than the sigma bond.

And the presence of a double bond increases the reactivity of a molecule

because you have now a bond that is weaker and can break easily.

The third characteristic is the electronegativity.

When two different atoms are engaged in a covalent bond,

one atom has a stronger pull on the electrons.

This property is called "electronegativity."

The difference of electronegativity determine the relative position

of the electrons in the molecular orbital between two atoms,

and that will affect the reactivity of the molecule in part--