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Learning Goals Associated with Winter_2021_Bis2A_Facciotti_Reading_12
- Define a redox reaction and identify common biological redox reactions.
- Given a redox
reaction, identify the reducing agent, oxidizingagent, moleculethat becomes oxidized, and the reduced species. Identify which species the electron (s) “starts” in,and to which species it “goes.”
- Write a composite chemical equation when given two redox half-reactions.
- Calculate the
ΔE 0’ for a givenredox reaction using the equation 0’ = E 0’ (oxidant) - (reductant)
- Predict whether a directional transfer of electrons between two chemical species is endergonic or exergonic by applying the concept of redox potential to
- Qualitatively relate the difference in redox potentials with a corresponding delta of Gibbs enthalpy.
- Define each variable and its role in the equation: ΔG0
’= - nFΔE 0’.
- Convert between ΔG0
’and 0’ for a givenredox reaction using the equation ΔG0’ = - nF 0’
- Tell an energy story for a redox reaction that
utilizesthe electron carrier NAD+/NADH as the second substrate in the simple, generic reaction scheme:AH + NAD+ -> A+ + NADH.
- Identify NAD+ from its molecular structure and identify the functional group involved in its function as an oxidizing or reducing agent.
Metabolism in General Biology
Cellular metabolism represents roughly 1/3 of the General Biology curriculum. You will learn about common chemical reactions that
What have we learned? How will it relate to metabolism?
- We have focused on the identification and chemical properties of common biological functional groups. As we dive into metabolism, this will help you be familiar with and sometimes even predict the chemical nature/reactivity of compounds you have never seen before.
- We have practiced recognizing and classifying molecules into four major functional groups. This will help you as we discuss how to build and break down these molecules.
- We have learned some basic thermodynamics. This gives us a common set of concepts with which to discuss whether a biochemical reaction or process is likely to occur, and if so in which direction and how fast. This will be critical as we consider some key reactions that take place in metabolism.
- We have learned and practiced the energy story rubric. This will allow us to study new biochemical reactions and to discuss them with a common, consistent language and approach
whichalso reinforces the lessons we learned about thermodynamics.
An overview of this section
- We will introduce an important concept called reduction
potentialand you will be giventhe opportunity to use a redox tower. There is also a discussion on redox chemistry in your discussion manual. Use both resources.
- We will introduce two major players in metabolism, ATP and NADH. We expect you to recognize their structures if shown on an exam.
- We will cover the metabolic pathway glycolysis. Keep in mind that we want you to look at any reaction and tell us an energy story of that reaction. You should not try to memorize these pathways (though it will help to remember some big picture things - we will stress these). Often we will give you the pathway as a figure on the exams. Glycolysis produces 2 ATP via a process called substrate level phosphorylation, 2 NADH and 2 pyruvate compounds.
- We will use the reactions of the TCA cycle to create multiple examples of energy stories. The TCA cycle will also produce more ATP, NADH and oxidize glucose into CO2.
- We will look at an alternative pathway to that of the TCA cycle, fermentation. Here, for the first time, we will see NADH used as a reactant in a metabolic reaction.
- We will follow NADH to the end of its journey, as it donates its electrons to the electron transport chain (ETC). In this module, you will need to use a redox tower. The ETC produces a proton gradient. No ATP
is directly generatedin this process. However, the proton gradient is then usedby the cell to run an enzyme called ATP synthase, which catalyzesthe reaction ADP + Pi --> ATP. This method of ATP production (called oxidative phosphorylation) results in more ATP being produced than through substrate level phosphorylation.
- And finally, we will go through the process of photosynthesis.
In this class, most of the oxidation/reduction reactions that we discuss occur in metabolic pathways (connected sets of metabolic reactions) where compounds consumed by the cell
Lets start with some generic reactions
Transferring electrons between two compounds results in one of these compounds loosing an electron and one compound gaining an electron. For example, look at the figure below. If we use the energy story rubric to look at the overall reaction, we can compare the before and after characteristics of the reactants and products. What happens to the matter (stuff) before and after the reaction? Compound
Put another way, when an electron
In Bis2A we expect you to become familiar with this terminology. Try to learn it and learn to use it as soon as possible - we will use the terms frequently and will not have the time to define them each time.
Remember the Definitions:
The Half Reaction
To formalize our common understanding of red/ox reactions, we introduce the concept of the half reaction. A full red/ox reaction requires two half reactions. We can think each half reaction as a description of what happens to one of the two molecules involved in the full red/ox reaction. We illustrate this below. In this example, compound AH is being oxidized by compound B+; electrons are moving from AH to B+ to generate A+ and BH. Each reaction can be thought of as two half reactions: Where AH is being oxidized and a second reaction where B+ is being reduced to BH. These two reactions are considered coupled, a term that shows that these two reactions occur together, at the same time.
By convention we analyze and describe red/ox reactions with respect to reduction potentials, a term that quantitatively describes the “ability” of a compound to gain electrons. This value of the reduction potential is determined experimentally but for the purpose of this course we assume that the reader will accept that the reported values are reasonably correct. We can anthropomorphize the reduction potential by saying that it is related to the strength with which a compound can “attract” or “pull” or “capture” electrons. Not surprisingly this is is related to but not identical to electronegativity.
What is this intrinsic property to attract electrons?
Different compounds, based on their structure and atomic composition have intrinsic and distinct attractions for electrons. This quality is termed reduction potential or E0’and is a relative quantity (relative to some “standard” reaction). If a test compound has a stronger "attraction" to electrons than the standard (if the two competed, the test compound would "take" electrons from the standard compound), we say that the test compound has a positive reduction potential whose magnitude is proportional to how much more it "wants" electrons than the standard compound. The relative strength of the compound compared to the standard is measured and reported in units of Volts (V)(sometimes written as electron volts or eV) or milliVolts (mV). The reference compound in most red/ox towers is H2.
Possible NB Discussion Point
Rephrase for yourself: How do you describe or think about the difference between the concept of electronegativity and red/ox potential?
The Red/ox Tower
All kinds of compounds can take part in red/ox reactions. Scientists have developed a graphical tool to tabulate red/ox half reactions based on their E0' values and to help us predict the direction of electron flow between potential electron donors and acceptors. Whether a particular compound can act as an electron donor (reductant) or electron acceptor (oxidant) depends critically on what other compound it is interacting with. The electron tower usually ranks a variety of common compounds (their half reactions) from most negative E0', compounds that readily get rid of electrons, to the most positive E0', compounds most likely to accept electrons. In addition, each half reaction is written by convention with the oxidized form on the left/followed by the reduced form on the right of the slash.
For example, we write the half reaction for the reduction of NAD+ to NADH:
NAD+/NADH. The tower below also lists the number of electrons that are transferred in each reaction. For example, the reduction of NAD+ to NADH involves two electrons, written in the table as 2e-.
A biochemical electron tower is shown below.
Acetate + CO2
ferredoxin (ox) version 1
ferredoxin (red) version 1
succinate + CO2 + 2H+
a-ketoglutarate + H2O
glyceraldehyde-3-P + H2O
ferredoxin (ox) version 2
ferredoxin (red) version 2
-0.42 (at [H+] = 10-7; pH=7)
Note: at [H+] = 1; pH=0 the Eo' for hydrogen is ZERO. You will see this in chemistry class.
α-ketoglutarate + CO2 + 2H+
Pyruvate + CO2
NAD+ + 2H+
NADH + H+
NADP+ + 2H+
NADPH + H+
Complex I FMN (enzyme bound)
Lipoic acid, (ox)
Lipoic acid, (red)
1,3 bisphosphoglycerate + 2H+
glyceraldehyde-3-P + Pi
FAD+ (free) + 2H+
Acetaldehyde + 2H+
Pyruvate + 2H+
Oxalacetate + 2H+
α-ketoglutarate + NH4+
FAD+ + 2H+ (bound)
Methylene blue, (ox)
Methylene blue, (red)
Fumarate + 2H+
CoQ (Ubiquinone - UQ + H+)
UQ + 2H+
Complex III Cytochrome b2; Fe3+
Cytochrome b2; Fe2+
Fe3+ (pH = 7)
Fe2+ (pH = 7)
Complex III Cytochrome c1; Fe3+
Cytochrome c1; Fe2+
Cytochrome c; Fe3+
Cytochrome c; Fe2+
Complex IV Cytochrome a; Fe3+
Cytochrome a; Fe2+
1/2 O2 + H2O
Complex IV Cytochrome a3; Fe3+
Cytochrome a3; Fe2+
Cytochrome f; Fe3+
Cytochrome f; Fe2+
Fe3+ (pH = 2)
Fe2+ (pH = 2)
1/2 O2 + 2H+
* Excited State, after absorbing a photon of light
GS Ground State, state prior to absorbing a photon of light
PS1: Oxygenic photosystem I
P840: Bacterial reaction center containing bacteriochlorophyll (anoxygenic)
PSII: Oxygenic photosystem II
Video on electron tower
For a short video on how to use the electron tower in red/ox problems click here or below. This video was made by Dr. Easlon for Bis2A students. (This is quite informative.)
What is the relationship between ΔE0' and ΔG?
The question now becomes: how do we know if any given red/ox reaction is energetically spontaneous or not (exergonic or endergonic) and regardless of direction, what the free energy difference is? The answer lies in the difference in the reduction potentials of the two compounds. The difference in the reduction potential for the reaction or E0' for the reaction, is the difference between the E0' for the oxidant (the compound getting the electrons and causing the oxidation of the other compound) and the reductant (the compound losing the electrons). In our generic example below, AH is the reductant and B+ is the oxidant. Electrons are moving from AH to B+. Using the E0' of -0.32 for the reductant and +0.82 for the oxidant the total change in E0' or ΔE0' is 1.14 eV.
Figure 3. Generic red/ox reaction with half reactions written with reduction potential (E0') of the two half reactions indicated.
The change in ΔE0' correlates to changes in Gibbs free energy, ΔG. In general a large positive ΔE0' is proportional to a large negative ΔG. The reactions are exergonic and spontaneous. For a reaction to be exergonic the reaction needs to have a negative change in free energy or -ΔG, this will correspond to a positive ΔE0'. In other words, when electrons flow "downhill" in a red/ox reaction from a compound with a lower (more negative) reduction potential to a second compound with a larger (more positive) reduction potential, they release free energy. The greater the voltage, E0', between the two components, the greater the energy available when electron flow occurs. It is, in fact, possible to quantify the amount of free energy available. The relationship is given by the Nernst equation:
Figure 4. The Nernst equation relates free energy of a red/ox reaction to the difference in reduction potential between the reduced products of the reaction and oxidized reactant.
Attribution: Marc T. Facciotti
- n is the number of moles of electrons transferred
- F is the Faraday constant of 96.485 kJ/V. Sometimes it is given in units of kcal/V which is 23.062 kcal/V, which is the amount of energy (in kJ or kcal) released when one mole of electrons passes through a potential drop of 1 volt
Introduction to Mobile Energy Carriers
Energy moves and transfers within the cell in a variety of ways. One critical mechanism that nature has developed is the use of recyclable molecular energy carriers. While there are several major recyclable energy carriers, they all share some common functional features:
Properties of Key Cellular Molecular Energy Carriers
- We think of the energy carriers as existing in "pools" of
availablecarriers. One could, by analogy, consider these mobile energy carriers analogous to the delivery vehicles of parcel carriers—the company has a certain "pool" of availablevehicles at any one time to pickup and make deliveries.
- Each individual carrier in the pool can exist in one of multiple distinct states: it is
eithercarrying a "load" of energy, a fractional load, or is "empty". The molecule can interconvertbetween "loaded" and empty and thus can be recycled. Again by analogy, the delivery vehicles can be eithercarrying packages or be empty and switch between these states.
- The balance or ratio in the pool between "loaded" and "unloaded" carriers is important for cellular function, is regulated by the cell, and can often tell us something about the state of a cell. Likewise, a parcel carrier service keeps close tabs on how full or empty their delivery vehicles are—if they are too full, there may be insufficient "empty" trucks to pick up new packages; if they are too empty, business must not be going well or they shut it down. There is an appropriate balance for different situations.
In this course, we will examine two major types of molecular recyclable energy carriers: (1) the adenine nucleotides: nicotinamide adenine dinucleotide (NAD+), a close relative, nicotinamide adenine dinucleotide phosphate (NADP+), and flavin adenine dinucleotide (FAD2+) and (2) nucleotide mono-, di-, and triphosphates, with particular attention paid to adenosine triphosphate (ATP). These two types of molecules participate in a variety of energy transfer reactions. We primarily associate adenine nucleotides with red/ox chemistry, and nucleotide triphosphates with energy transfers linked to the hydrolysis or condensation of inorganic phosphates.
Red/oxchemistry and electron carriers
The oxidation of, or removal of an electron from, a molecule (whether accompanied with the removal of an accompanying proton or not) results in a change of free energy for that molecule—matter, internal energy, and entropy have all changed. Likewise, the reduction of a molecule also changes its free energy. The magnitude of change in free energy and its direction (positive or negative) for a red/ox reaction dictates the spontaneity of the reaction and how much energy it transfers. In biological systems, where a great deal of energy transfer happens via red/ox reactions, it is important to understand how these reactions
Note: DESIGN CHALLENGE
The problem alluded to in the previous discussion question is a great place to bring in the design challenge rubric. If you recall, the first step of the rubric asks that you define a problem or question. Here, let's imagine that there is a problem to define for which the mobile electron carriers below helped Nature solve.
***Remember, evolution DOES NOT forward-engineer solutions to problems, but in retrospect, we can use our imagination and logic to infer that what we see preserved by natural selection provided a selective advantage, because the natural innovation "solved" a problem that limited success.***
Design challenge for red/ox carriers
- What was a problem
(s) that the evolution of mobile electron carriers helped solve?
- The next step of the design challenge asks you to identify criteria for successful solutions. What are criteria for success in the problem you've identified?
- Step 3 in the design challenge asks you to identify solutions. Well, here Nature has identified some for us—we consider three in the reading below. It looks like Nature is happy to have multiple solutions to the problem.
- The penultimate step of the design challenge rubric asks you to test the proposed solutions against the criteria for success. This should make you think/discuss why there are multiple different electron carriers. Are there different criteria for success? Are they each solving slightly different problems? What do you think? Be on the lookout as we go through metabolism for clues.
NAD+/H and FADH/H2
In living systems, a small class of compounds function as electron shuttles: they bind and carry electrons between compounds in different metabolic pathways. The principal electron carriers we will consider derive from the B vitamin group and nucleotides. These compounds can both become reduced (that is, they accept electrons) or oxidized (they lose electrons) depending on the reduction potential of a potential electron donor or acceptor that they might transfer electrons to and from. Nicotinamide adenine dinucleotide (NAD+) (we show the structure below) derives from vitamin B3, niacin. NAD+ is the oxidized form of the molecule; NADH is the reduced form of the molecule after it has accepted two electrons and a proton (which together are the equivalent of a hydrogen atom with an extra electron).
We are expecting you to memorize the two forms of NAD+/NADH, know which form is oxidized and which is reduced, and be able to recognize either form on the spot in a chemical reaction.
NAD+ can accept electrons from an organic molecule according to the general equation:
Here is some vocabulary review: when electrons are added to a compound, we say the compound has been reduced. A compound that reduces (donates electrons to) another is called a reducing agent. In the above equation, RH is a reducing agent, and NAD+ becomes reduced to NADH. When electrons leave a compound, it becomes oxidized. A compound that oxidizes another is called an oxidizing agent. In the above equation, NAD+ is an oxidizing agent, and RH is oxidized to R. Put another way, the reducing agent gets oxidized and the oxidizing agent gets reduced.
You need to get this down! We will (a) test specifically on your ability to do so (as "easy" questions), and (b) we will use the terms with the expectation that you know what they mean and can relate them to biochemical reactions correctly (in class and on tests).
You will also encounter a second variation of NAD+, NADP+. It is structurally very similar to NAD+, but it contains an extra phosphate group and plays an important role in anabolic reactions, such as photosynthesis. Another nucleotide-based electron carrier that you will also encounter in this course and beyond, flavin adenine dinucleotide (FAD+), derives from vitamin B2, also called riboflavin. Its reduced form is FADH2. Learn to recognize these molecules as electron carriers.
Figure 1. The oxidized form of the electron carrier (NAD+) is shown on the left, and the reduced form (NADH) is shown on the right. The nitrogenous base in NADH has one more hydrogen ion and two more electrons than in NAD+.
The cell uses NAD+ to "pull" electrons off of compounds and to "carry" them to other locations within the cell; thus we call it an electron carrier. Many metabolic processes we will discuss in this class involve NAD(P)+/H compounds. For example, in its oxidized form, NAD+ is used as a reactant in glycolysis and the TCA cycle, whereas in its reduced form (NADH), it is a reactant in fermentation reactions and electron transport chains (ETC). We will discuss each of these processes in later modules.
Energy story for a red/ox reaction
***As a rule of thumb, when we see NAD+/H as a reactant or product, we know we are looking at a red/ox reaction.***
When NADH is a product and NAD+ is a reactant, we know that NAD+ has become reduced (forming NADH); therefore, the other reactant must have been the electron donor and become oxidized. The reverse is also true. If NADH has become NAD+, then the other reactant must have gained the electron from NADH and become reduced.
Figure 2. This reaction shows the conversion of pyruvate to lactic acid coupled with the conversion of NADH to NAD+. Source: https://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme/sequential_reactions
In the figure above, we see pyruvate becoming lactic acid, coupled with the conversion of NADH into NAD+. LDH catalyses this reaction. Using our "rule of thumb" above, we categorize this reaction as a red/ox reaction. NADH is the reduced form of the electron carrier, and NADH is converted into NAD+. This half of the reaction results in the oxidation of the electron carrier. Pyruvate is converted into lactic acid in this reaction. Both sugars are negatively charged, so it would be difficult to see which compound is more reduced using the charges of the compounds. However, we know that pyruvate has become reduced to form lactic acid, because this conversion is coupled to the oxidation of NADH into NAD+. But how can we tell that lactic acid is more reduced than pyruvate? The answer is to look at the carbon-hydrogen bonds in both compounds. As electrons transfer, they are often accompanied by a hydrogen atom. Pyruvate has a total of three C-H bonds, while lactic acid has four C-H bonds. When we compare these two compounds in the before and after states, we see that lactic acid has one more C-H bond; therefore, lactic acid is more reduced than pyruvate. This holds true for multiple compounds. For example, in the figure below, you should be able to rank the compounds from most to least reduced using the C-H bonds as your guide.
Figure 3. Above are a series of compounds than can be ranked or reorganized from most to least reduced. Compare the number of C-H bonds in each compound. Carbon dioxide has no C-H bonds and is the most oxidized form of carbon we will discuss in this class. Answer: the most reduced is methane (compound 3), then methanol (4), formaldehyde (1), carboxylic acid (2), and finally carbon dioxide (5).
Figure 4. This reaction shows the conversion of G3P, NAD+, and Pi into NADH and 1,3-BPG. This reaction is catalyzed by glyceraldehyde-3-phosphate dehydrogenase.
Energy story for the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase:
Lets make an energy story for the reaction above.
First, let us characterize the reactants and products. The reactants are glyceraldehyde-3-phosphate (a carbon compound), Pi (inorganic phosphate), and NAD+. These three reactants enter a chemical reaction to produce two products, NADH and 1,3-bisphosphoglycerate. If you look closely, you can see that the 1,3-BPG contains two phosphates. This is important since a chemical reaction should lose no mass between its beginning and its end. There are two phosphates in the reactants, so there must be two phosphates in the products (conservation of mass!). You can double check the book keeping of mass for all other atoms. It should also tabulate correctly. An enzyme called glyceraldehyde-3-phosphate dehydrogenasethat catalyzes this reaction. The standard free energy change of this reaction is ~6.3 kJ/mol, so under standard conditions, we can say that the free energy of the products is higher than that of the reactants and that this reaction is not spontaneous under standard conditions.
What can we say about this reaction when it is catalyzed by glyceraldehyde-3-phosphate dehydrogenase?
This is a red/ox reaction. We know that because we have produced a reduced electron carrier (NADH) as a product and NAD+ is a reactant. Where did the electron come from to make NADH? The electron must have come from the other reactant (the carbon compound).