BIOCHEMISTRY DISCUSSION 6
Biochemistry: A Short Course Fourth Edition CHAPTER 15 Metabolism: Basic Concepts and Design
Tymoczko • Berg • Gatto • Stryer
© 2019 W. H. Freeman and Company.
All right - so now that we've discussed how we got these small molecules into our systems, we have the lipids, the monosaccharides from the carbohydrates, and the amino acids from the proteins, all circulating through our blood, and then they get processed further and turned into energy. And that's what we call metabolism. So this is actually the meat of biochemistry. More or less everything we've talked about up to this point is background. Now it's all going to come together and we're going to really do some biochemistry here.
{Note: I object to the use of the term “Design” here, because it is misleading. The systems were not “designed”, they evolved. But I hear scientists, even ones that I really respect, talking in these terms. I slip into it myself! It is easier to relate to, but it is essentially flawed, and I try to avoid it.}
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Chapter 15: Outline
15.1 Energy Is Required to Meet Three Fundamental Needs
15.2 Metabolism Is Composed of Many Interconnecting Reactions
15.3 ATP Is the Universal Currency of Free Energy
15.4 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
15.5 Metabolic Pathways Contain Many Recurring Motifs
15.6 Metabolic Processes Are Regulated in Three Principal Ways
We'll start out by talking about the fundamental uses of energy in the body and we'll talk about how metabolism is a lot of different reactions, an enormous number of different reactions, all connected. We'll talk about ATP, which you probably already know about a little bit, but that's where most of our energy is stored and transferred. And “oxidation of carbon fuels” - that would be your carbohydrates, and also the lipids, the fatty acids, are considered carbon fuels; so that's excluding the amino acids. The amino acids can be also used as fuels but we're not talking about that in this chapter {or this class, really}. Then, there’s “metabolic pathways contain many recurring motifs”. So we'll talk about what some of those motifs are. And “metabolic processes are regulated in three principal ways”. And so we'll talk about the regulation of metabolic processes.
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Energy is required to power muscle contraction, cell movement, and biosynthesis.
Phototrophs obtain energy by capturing sunlight.
Chemotrophs obtain energy through the oxidation of carbon fuels.
Basic principles:
Molecules are degraded or synthesized stepwise in a series of reactions (termed metabolic pathways).
ATP is the energy currency of life.
ATP can be formed by the oxidation of carbon fuels.
Although many reactions occur inside a cell, there are a limited number of reaction types involving particular intermediates that are common to all metabolic pathways.
Metabolic pathways are highly regulated.
15.1 Energy Is Required to Meet Three Fundamental Needs Basic Principles Govern Energy Manipulation in All Cells
Energy is required to power muscle contraction, cell movement, and biosynthesis. But really it's all about movement. Muscle contraction is movement. It's movement of the molecules that are coordinated in such a way that they result in large scale movements of the body. Cell movement is small scale movement. And biosynthesis is basically the pushing together or pulling apart of atoms and molecules to create new atoms and molecules. And that energy to push them together or pull them apart has to come from somewhere.
Now, ultimately all of the energy that we get comes from the Sun. Phototrophs obtain energy by capturing sunlight ("photo-" is light, and ”-troph" is eat). So things that eat light, like plants, those are able to extract the energy from the sunlight and use that to grab carbon from carbon dioxide in the air and use that carbon to build itself, to create more of itself, to grow and reproduce. The energy required to extract that carbon comes from sunlight. We're not talking about that in detail in this course. We’ve decided to focus on animal and, more specifically, human reactions, and to go light on the plants. Because, honestly, human reactions are plenty - they are extremely complex and we are going to cover them in some great depth and there's just not enough time to cover everything. But it is important to notice that there are lots of other different ways of getting energy in the plant and animal world and those are fascinating things to study and I encourage you to look into them. You can also read about them in your textbook but I won't be talking about phototrophs much in this course.
Chemotrophs, that's obtaining energy through oxidation of, well, carbon fuels. And that is actually how most of the rest of us, all the animals at least, get our energy. We take the carbon that has been accumulated by the phototrophs, and use that to build ourselves, to grow and reproduce. But we wouldn't have those carbon fuels if it weren't for the carbon collecting activities of the phototrophs. WE cannot transfer carbon dioxide directly into carbon molecules.
So those basic principles that we list here:
1. Molecules are degraded or synthesized in a series of reactions, which we call the metabolic pathways. And we will discuss several of those metabolic pathways.
2. ATP is the “energy currency of life”. It's the molecule that is the most common storage form - well, I mean, there's a lot of different molecules that store energy, but ATP is the biggest one that's used for facilitating chemical reactions in the body. And there are many reasons for that and I'll try to go into some of that in some detail.
3. ATP can be formed by the oxidation of carbon fuels. That is, well, it's more formed by extracting the energy from the oxidation of carbon fuels. But yes, that's where we get our ATP. But that’s not to say that you can just oxidize carbon fuels and ATP pops out. There’s a lot of different reactions that lead from the oxidation of carbon fuels to the formation of ATP.
4. But there are also some very common reactions that occur in lots of different places in these different pathways. And so we'll be talking about some of those more common reactions and how they work together.
5. And then, metabolic pathways are highly regulated. When you have enough ATP, you need to stop making ATP, and instead use that glucose to make glycogen as a storage form so you can save it for later. That's just an example of why these things need to be regulated. But we'll talk about many more.
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Diagram of the Stages of Catabolism
Figure 15.1 Stages of catabolism. The extraction of energy from fuels can be divided into three stages.
So here's the general process. And the first stage that we see at the top is digestion, which we've discussed already. The second stage is the processing of the individual fatty acids, glucose molecules, and amino acids, into acetyl CoA. And acetyl CoA - remember coenzyme A is not actually made during this process. Coenzyme A is just something that the acetyl groups get attached to. What it {Stage 2} is basically doing is breaking down these things into acetyl groups. And acetyl groups have two carbons and an oxygen, and then those two carbons and an oxygen get broken down further to completion in the citric acid cycle. And those produce carbon dioxide and electrons - high energy electrons which are then transferred to oxygen in the process of oxidative phosphorylation, which creates a great deal of ATP. It's that last step that is responsible for most of the ATP generated. But right now we're going to talk about the Stage 2, which is glycolysis … we're going to focus mainly on glucose and its processing into the acetyl groups that will then be passed along to Stage 3.
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Diagram of Glucose Metabolism
Figure 15.2 Glucose metabolism. Glucose is metabolized to pyruvate in 10 linked reactions. Under anaerobic conditions, pyruvate is metabolized to lactate and, under aerobic conditions, to acetyl CoA. The glucose-derived carbon atoms of acetyl CoA are subsequently oxidized to CO2.
Probably the most important of the reactions, or series of reactions, in metabolism is glycolysis. And that's what we're going to talk about right here. Glucose, at the top, gets turned into pyruvate. And there’s ten steps that occur to make glucose into pyruvate. And then pyruvate can be changed into either lactate or it can be broken down further releasing carbon dioxide. You see the carboxylic acid group there on pyruvate with the minus sign next to it? See how close that is to carbon dioxide? Well, that's what happens, is that, that group breaks off and becomes carbon dioxide, and the coenzyme A comes in and takes over that bond. And then, there's two pathways that pyruvate can be processed into, and that’s the anaerobic which takes it to lactate, and the aerobic which requires oxygen. And that is where you have your acetyl CoA and proceed to metabolize these carbon products further.
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Diagram of Metabolic Pathways
Figure 15.3 Metabolic pathways. [From the Kyoto Encyclopedia of Genes and Genomes (www.genome.ad.jp/kegg).]
And this diagram also shows several of the sources of the energy, starting with complex carbohydrates up at the upper left. There's vitamins and cofactors which get broken down and metabolized. Nucleotides, like adenine, guanine. Complex lipids - long hydrocarbon chains which need to get broken down into smaller hydrocarbon chains and then be processed by lipid metabolism. Then there's amino acid metabolism - amino acids can actually be broken down and metabolized as well. And other substances. And in the lower left hand corner, you see energy metabolism, that would be the processes of photosynthesis that we're not going to be talking about.
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To explore, go to http://biochemical-pathways.com/#/map/1
METABOLISM – MORE COMPLETE
In Depth Look at Metabolism
For a slightly more in depth look at metabolism, you can look at this diagram and you can see how complicated it actually is. There are all of these processes going on in the cell simultaneously and interacting with each other. And for this reason, actually, this is one of the reasons that I think we need computers to study these things because I don't think anybody could fully understand how this all works. But this is just a little peek behind the curtain for you.
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15.2 Metabolism Is Composed of Many Interconnecting Reactions Metabolism Consists of Energy-Yielding Reactions and Energy-Requiring Reactions
Metabolic pathways can be divided into two types:
Catabolic pathways combust carbon fuels to synthesize ATP or ion gradients.
Anabolic pathways use ATP and reducing power to synthesize large biomolecules.
Although anabolic and catabolic pathways may have reactions in common, the regulated, irreversible reactions are always distinct.
So there are energy-requiring reactions in metabolism, and then there are energy-yielding reactions in metabolism. And there are a whole bunch of other reactions which just kind of happen. They don't really require or make {a significant amount of} energy. But generally speaking there are these pathways called catabolic pathways that break down fuels and make ATP, and then there are anabolic pathways that use ATP and other sources of energy to synthesize large biomolecules. So they are distinct pathways. And there are sometimes common elements between the pathways, but the big steps, where you break apart an ATP for example, those are usually considered irreversible because they lose so much energy that it would be very unlikely for that to happen backwards. And since those steps are irreversible they are highly regulated.
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A Thermodynamically Unfavorable Reaction Can Be Driven by a Favorable Reaction
In order to construct a metabolic pathway, two criteria must be met:
The individual reactions must be specific.
The pathway in total must be thermodynamically favorable.
A thermodynamically unfavorable reaction in a pathway can be made to occur by coupling it to a more favorable reaction.
All right - now here is the key concept for all of the stuff that's going to follow. And that is:
A thermodynamically unfavorable reaction can be driven by a favorable reaction.
Now, here's the way to think about this. Let's look at the diagram at the bottom of the slide. A goes to B + C. And that reaction requires 21 kilojoules per mole. B goes to D. And that reaction releases 34 kilojoules per mole. So if you take A and go from A to C + D, then, the overall reaction is -13 kilojoules per mole. And because the overall reaction energy is negative, then, the reaction can proceed.
So another way of thinking about this would be, alright, let’s look at the A, the A train has a bunch of wood in it, and it wants to get up the hill to point C. So A wants to get to a Bunch of wood and C {B + C}. That is not going to happen because there's a large hill there in front of the train. And it takes a lot of energy to get that train up the hill. But if you take that Bundle of wood and burn it, then you're releasing a lot of energy {B goes to D + 34 kJ/mol}. And if you release enough energy to get that train up the hill, then you get your A train up on top of the hill {C} with a bunch of burnt wood {D}. And that's the overall reaction: A goes to C + D. {Actually, I don’t like this analogy any more. Please ignore it completely.}
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Section 15.3 ATP Is the Universal Currency of Free Energy
Learning objective 3: Identify the factors that make ATP an energy-rich molecule.
Learning objective 4: Explain how ATP can power reactions that would otherwise not take place.
Energy derived from fuels or light is converted into adenosine triphosphate (ATP), the cellular energy currency.
Now, the wood in most of these reactions will be ATP. And that is the common form of energy that we use to power these unfavorable reactions in the cell.
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ATP Hydrolysis Is Exergonic
The hydrolysis of ATP is exergonic because the triphosphate unit contains two phosphoanhydride bonds that are unstable.
The energy released on ATP hydrolysis is used to power a host of cellular functions.
ATP + H2O ⇌ ADP + Pi
ΔG°ʹ = –30.5 kJ/mol (–7.3 kcal/mol)
ATP + H2O ⇌ AMP + PPi
ΔG°ʹ = –45.6 kJ/mol (–10.9 kcal/mol)
Now, when ATP is broken apart - and the process of breaking it apart is hydrolysis, using a water molecule to break off phosphate groups - that is exergonic; it releases energy because there's a lot of energy stored up in that ATP molecule. And therefore when you break those bonds, that energy gets released, and quite a bit of energy gets released. Hydrolysis of ATP to ADP releases 30.5 kilojoules per mole of energy. And the hydrolysis of ATP to AMP (which is adenosine monophosphate) releases 45.6 kilojoules per mole. Although this is not an extraordinary amount of energy, it's enough to power most of the reactions, all of the reactions of glycolysis for example. So it's a very useful amount of energy.
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Structures of ATP, ADP, and AMP
Figure 15.4 Structures of ATP, ADP, and AMP. These adenylates consist of adenine (blue); a ribose (black); and a tri-, di-, or monophosphate unit (red). The innermost phosphorus atom of ATP is designated Pα, the middle one Pβ, and the outermost one Pγ.
Just taking a quick look here at the structure of ATP. You see the phosphate groups on the left hand side, is the alpha, beta, and gamma phosphates, labeled as they go away from the ribose sugar. And when you break it down into ADP, you see there's only two phosphates. AMP, monophosphate, has one phosphate. That's where all this energy is. It's in those phosphates. The rest of the molecule is really just a handle so that the cell can pass this energy around. That structure, the ribose and the adenine residue, is one of the most common structures in the cell. That's what our DNA is made of and proteins can recognize that structure very easily. So it makes a very convenient handle for passing around the phosphates.
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ATP Hydrolysis Drives Metabolism by Shifting the Equilibrium of Coupled Reactions
Consider the following endergonic reaction:
Coupling this reaction with ATP hydrolysis renders the formation of B exergonic.
I'm just going to walk you through an example here of how this might work. So the reaction at the top, look at it closely, you see A goes to B. And B goes back to A. But for A to go to B, it requires an input of 16.7 kilojoules per mole of energy. So the equilibrium constant for this is 1.15 x 10^-3. So that is, the ratio at equilibrium of the product, B, to the reactants, A, will be about one to a thousand. So there'll be about a thousand times as much reactant as there is product.
Now let’s look what happens if we couple this to ATP hydrolysis. So instead of just A going to B, we have A + ATP + H2O goes to B + ADP + inorganic phosphate (and that’s what the Pi stands for, is phosphate {P} with an “i” for inorganic which means it's not connected to any carbon - that's all that “organic” means is that it's got carbon in it, basically). So THAT overall reaction has a release of energy of 13.8 kilojoules per mole. So overall, that reaction is favorable and the equilibrium constant for that ends up being 2.67 x 10^2, which is about 200 - ten {actually 23.2} thousand times more than it was without the ATP. So by simultaneously breaking apart an ATP molecule you are able to vastly increase the amount of product that you create.
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The High Phosphoryl-Transfer Potential of ATP Results from Structural Differences Between ATP and Its Hydrolysis Products (1/2)
Phosphoryl-transfer potential―the standard free energy of hydrolysis―is a means of comparing the tendency of organic molecules to transfer a phosphoryl group to an acceptor molecule.
ATP has a high phosphoryl-transfer potential because of three key factors (we are ignoring the contribution of entropy):
Charge repulsion
Resonance stabilization
Stabilization by hydration
Why does ATP have so much energy in it? Well, we call the energy that is stored in ATP “phosphoryl-transfer potential” - so it's the potential energy of transferring that phosphate group to something else. And something else would also include water, so hydroxide {making Pi}. So let's compare ATP breaking down into ADP plus inorganic phosphate. The energy released there is -30.5 kilojoules per mole. Another phospho-structure, glycerol-3-phosphate, that's just a glycerol with a phosphate group attached to it, can break down but it only releases -9.2 kilojoules per mole of energy. So why is so much more energy released when you break down ATP? Well, there's three main reasons:
1. Charge repulsion
2. Resonance stabilization
3. Stabilization by hydration
So let's talk about these in turn.
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CHARGE REPULSION
Charge Repulsion
Charge repulsion is the most obvious one. Take a look at that adenosine triphosphate there on the left. And you see how many charges there are on it. There's four negative charges. Well, negative charges repel each other. So basically those phosphate groups are stuck on there but they're “spring loaded” - so that as soon as that bond breaks they'll pop off with a lot of force. That force can then be used to drive other reactions. Compare that to the glycerol-3-phosphate. It has a phosphate group on there, but there are only two negative charges, and there are some other oxygens, but not nearly as much charge repulsion as you see in the adenosine triphosphate. So some energy will be released when you pop off that phosphate, but not as much. So if you break that bond, the phosphate and the remaining glycerol will fly apart but not nearly as fast.
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Resonance Stabilization
Figure 15.5 Resonance structures of orthophosphate.
Resonance stabilization is a little bit more difficult to understand, but it's basically the ability of the electrons to spread out over the molecule. An inorganic phosphate just sitting there, the electrons can spread out more or less evenly amongst all the oxygens that are on the phosphate.
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Improbable Resonance Structure
Figure 15.6 Improbable resonance structure. There are fewer resonance structures available to the γ-phosphate of ATP than to free orthophosphate.
With ATP however, (which is represented in this diagram as an AMP, a monophosphate with two additional phosphates attached to it, for a total of three) there are fewer resonance structures available. So there's three resonance structures that can be seen, but the fourth one on the right is highly unlikely because you have a positive charge on the oxygen. And so that means that the electrons have to spend their time on basically three oxygens instead of four, which constrains them to a smaller space. And that gives them - you know, they repel each other, so that's where the energy comes from due to resonance stabilization.
And quickly mention in passing - hydration. When you break apart ATP, you have more interaction of the ADP and phosphate with water, and therefore that actually is more favorable than if we have all three phosphates attached to each other. However, I think the difference that you would find between glycerol and the ADP as far as the hydration goes is probably minimal.
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Phosphoryl-Transfer Potential Is an Important Form of Cellular Energy Transformation
ATP has a phosphoryl-transfer potential that is intermediate among the biologically important phosphorylated molecules. This intermediate position enables ATP to function efficiently as a carrier of phosphoryl groups.
Now, ATP has good phosphoryl-transfer potential, there's a lot of energy in it, but it's not the most. It doesn't have the highest phosphoryl-transfer potential out of all the things in the body.
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Diagram Showing ATP Has a Central Position in Phosphoryl-transfer Reactions
Figure 15.7 ATP has a central position in phosphoryl-transfer reactions. The role of ATP as the cellular energy currency is illustrated by its relation to other phosphorylated compounds. ATP has a phosphoryl-transfer potential that is intermediate among the biologically important phosphorylated molecules. High-phosphoryl-transfer-potential compounds (1,3-BPG, PEP, and creatine phosphate derived from the metabolism of fuel molecules are used to power ATP synthesis. In turn, ATP donates a phosphoryl group to other biomolecules to facilitate their metabolism. [After D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry, 5th ed. (W. H. Freeman and Company, 2009), Fig. 13-19.]
Phosphoenolpyruvate actually has quite a bit more phosphoryl-transfer potential {than ATP}, as does 1,3-biphosphoglycerate, and creatine phosphate - so these actually are compounds that have higher energy. But those compounds can then be used to make ATP, and then that ATP can be used to phosphorylate glucose and glycerol to create glucose 6-phosphate and glycerol 3-phosphate. You wouldn't necessarily usually want to release all of that energy at once, because if you broke a phosphoenolpyruvate, you would have so much energy that a lot of it would probably go to waste. ATP is a nice intermediate-level energy storage molecule that is able to have broad effects in the cell.
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Clinical Insight: Exercise Depends on Various Means of Generating ATP
CLINICAL INSIGHT
Exercise Depends on Various Means of Generating ATP
Muscle contains only enough ATP to power muscle contraction for less than a second.
Creatine phosphate can regenerate ATP from ADP, allowing a short burst of activity as in a sprint.
Once the creatine phosphate stores are depleted, ATP must be generated by metabolic pathways.
Now this one is kind of a mind blower. You need ATP to run your muscles, but your muscles actually, at any given time, only have enough ATP to power their contraction for less than a second. So that means they must be making ATP continuously in order to support any kind of exercise or movement, and very rapidly. One of the ways that it makes ATP is using creatine phosphate. It has creatine phosphate stores in the muscle cells, and as you saw on the previous slide, creatine phosphate has a higher phosphoryl-transfer potential than ATP. So you can very rapidly make ATP from creatine phosphate. That reaction is mediated by the enzyme creatine kinase. But once the creatine phosphate is all gone, you need to get your ATP in other ways.
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Section 15.4 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Learning objective 5: Describe the relation between the oxidation state of a carbon molecule and its usefulness as a fuel.
ATP is the immediate donor of free energy for biological activities.
However, the amount of ATP is limited.
Consequently, ATP must be constantly recycled to provide energy to power the cell.
ATP is usually made out of ADP and inorganic phosphate, so those ADP molecules are being constantly recycled.
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Diagram of the ATP–ADP Cycle
Figure 15.10 The ATP–ADP cycle. This cycle is the fundamental mode of energy exchange in biological systems.
As you can see here, the breakdown of ATP to ADP powers motion and active transport, biosynthesis, and signal amplification, and to get back to ATP requires the oxidation of fuel molecules or, in the case of plants, photosynthesis.
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Carbon Oxidation Is Paired with a Reduction
Oxidation reactions involve loss of electrons. Such reactions must be coupled with reactions that gain electrons. The paired reactions are called oxidation–reduction reactions, or redox reactions.
The carbon atoms in fuels are oxidized to yield CO2, and the electrons are ultimately accepted by oxygen to form H2O.
The more reduced a carbon atom is, the more free energy is released upon oxidation.
Fats are a more efficient food source than glucose because fats are more reduced.
So carbon {oxidation} is paired with a reduction. And oxidation is the loss of electrons. The most common way to lose electrons is to attach an oxygen to things, because oxygens are so electronegative that the electrons become attached/associated with the oxygens. And that's why we call it oxidation. But there are many oxidation reactions which involve the transfer of electrons from one compound to another. And so the transfer or loss of electrons from one compound is called oxidation, and the gain of those electrons by the other compound is called reduction. And these are oxidation-reduction reactions. You might think of reductions as reducing the charge by making it more negative, by giving it electrons, I don't know if that would be helpful or not. The carbon atoms, when they are completely oxidized, make carbon dioxide. And the electrons from the carbon atoms go to the oxygen, to O2, and then the O2 {with a negative charge} will absorb hydrogens from the mix and create water. So the more reduced a carbon atom is, in other words, the more electrons it has associated with it, the more free energy can be released when it's oxidized. Fats are extremely reduced because they have a great deal of carbon-carbon and carbon-hydrogen bonds, whereas glucose has a lot of oxygen in it already, and therefore is partially oxidized already. Those oxygens on the glucose, though, make it easier to oxidize the glucose completely, and so a faster method of getting energy.
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Diagram of the Free Energy of Oxidation of Single-carbon Compounds
YIELD: 117
180
238
285
Figure 15.11 Free energy of oxidation of single-carbon compounds.
So here is a chart showing the free energy of oxidation of methane, and that means that if you were to completely oxidize methane to carbon dioxide, you would get 820 kilojoules per mole, which is a lot. Remember ATP is just 30 kilojoules per mole to make ADP. If you go from methane to methanol then you can get 117 kilojoules per mole. Go from methanol to formaldehyde you get 180 kilojoules per mole. Formaldehyde to formic acid is even more, 238. And then, formic acid to carbon dioxide is 285. And that is a lot of energy that you can get by oxidizing carbon.
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Structures of Prominent Fuels
GET MORE ENERGY FROM FATS
Figure 15.12 Prominent fuels. Fats are a more efficient fuel source than carbohydrates such as glucose because the carbon in fats is more reduced.
So remember we had glucose which is already partially oxidized. Fatty acids, though, the carbons are not oxidized at all, so you can get more energy from fats than you can from sugars.
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Compounds with High Phosphoryl-Transfer Potential Can Couple Carbon Oxidation to ATP Synthesis
The essence of catabolism is capturing the energy of carbon oxidation as ATP.
Oxidation of the carbon atom may form a compound with high phosphoryl-transfer potential that can then be used to synthesize ATP.
So you can use this energy from the oxidation of carbon to make ATP. And that's basically the whole process of metabolism, is that you need to take these carbon compounds which have carbon bonds, oxidize the carbons, and then harness that energy to make ATP.
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Section 15.5 Metabolic Pathways Contain Many Recurring Motifs
Activated Carriers Exemplify the Modular Design and Economy of Metabolism
ATP is an activated carrier of phosphoryl groups. Other activated carriers are common in biochemistry, and often they are derived from vitamins.
Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) carry activated electrons derived from the oxidation of fuels.
So we'll talk about activated carriers of energy. And ATP is an activated carrier but there are some other activated carriers that we'll talk about in quite a lot of detail. One of these is nicotinamide adenine dinucleotide (NAD+). Once again, it's got an adenine in it, surprise, surprise - a very good molecule for passing things around. And flavin adenine dinucleotide. These are used to carry high energy electrons that you get from the oxidation of carbon and take them to where they can make ATP.
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Structure of a NAD+
Figure 15.13 A nicotinamide-derived electron carrier. (A) Nicotinamide adenine dinucleotide (NAD+) is a prominent carrier of high-energy electrons derived from the vitamin niacin (nicotinamide) shown in red. (B) NAD+ is reduced to NADH.
Here's the structure of NAD+. And you can see the bottom portion looks almost like an ATP. It's like an ADP, but it's got a ribose and then that's a nicotinamide group attached to it. That nicotinamide can have two electrons attached to it and create NADH. Of course, there’s protons that get associated with it as well - but the high energy electrons are the important energy-carrying parts of this process.
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A Redox Dehydrogenation Reaction
So you can take a carbon that's got one oxygen on it, and an NAD+ with only 2 electrons, and you can oxidize that carbon further and create NADH, which has the extra electrons on it.
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The Structure of the Oxidized Form of Flavin Adenine Dinucleotide (FAD)
Figure 15.14 The structure of the oxidized form of flavin adenine dinucleotide (FAD). This electron carrier consists of the vitamin riboflavin (shown in blue) and an ADP unit (shown in black).
Flavin adenine dinucleotide, very similar also to ATP - it's like ADP but with this flavin group on it, derived from the vitamin riboflavin. FAD has two reactive sites. These reactive sites are next to double bonded nitrogens, so that those double bonds can come up and join the incoming electrons to create new bonds.
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FAD as an Electron Acceptor
So you can take a carbon bond and oxidize it by removing two electrons, making it into a double bond, and then add those two electrons to FAD to form FADH2.
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Structures of the Reactive Parts of FAD and FADH2
Figure 15.15 Structures of the reactive parts of FAD and FADH2. The electrons and protons are carried by the isoalloxazine ring component of FAD and FADH2.
...and here we can see the oxidized and reduced forms of FAD.
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Nicotinamide Adenine Dinucleotide Phosphate
Activated Carriers Exemplify the Modular Design and
Economy of Metabolism
Nicotinamide adenine dinucleotide phosphate (NADP+) is an activated carrier of electrons for reductive biosyntheses.
Another similar carrier is nicotinamide adenine dinucleotide phosphate (NADP+), which is often used to carry electrons for biosynthesis. That's opposed to NAD+ and FAD which generally carry electrons during metabolism to generate ATP.
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Keto Group of a Two-carbon Unit Being Reduced to a Methylene Group
Reductive biosynthesis – the making of fats
In biosynthesis you can take a carbonyl bond and turn it into a CH2 by adding four electrons, and that would be something that would be mediated by NADPH.
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The Structure of Nicotinamide Adenine Dinucleotide Phosphate (NADP+)
Figure 15.16 The structure of nicotinamide adenine dinucleotide phosphate (NADP+). NADP+ provides electrons for biosynthetic purposes. Notice that the reactive site is the same in NADP+ and NAD+.
Here we have a diagram of {NADP+}. It's essentially the same as NAD+ except at the bottom there you can see attached to the ribose there's an extra phosphate group. That I think is probably just there to distinguish it from NAD+ because the two molecules have different roles in the cell and there's got to be a way to tell them apart. The reactive site is the same in both of them, which is up there at the top, and when you add the two electrons and a proton you call it NADPH.
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Coenzyme A
Activated Carriers Exemplify the Modular Design and Economy of Metabolism
Coenzyme A (CoA or CoA-SH) is an activated carrier of acyl groups such as the acetyl group.
The transfer of the acyl group is exergonic because the thioester is unstable.
Ah! Coenzyme A. This is the famous acetyl CoA cofactor. And that is something that can carry around acetyl groups, which are the breakdown products of glucose in the glycolytic cycle. The transfer of this acetyl group is actually exergonic because the bond that's formed between the acetyl group and the coenzyme A is unstable. It's sort of a high energy bond right there.
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The Structure of Coenzyme A
Figure 15.17 The structure of coenzyme A (CoA-SH).
Here's the structure of coenzyme A. And wow - look at that on the right. It is still your old good friend adenine {adenosine}. The adenine {adenosine} diphosphate with an extra phosphate attached to the ribose - just your common motif for passing around energetic molecules. Next to that is a pantothenate unit, whose purpose I really don't know, and then the reactive group at the very end is the sulfur. And that sulfur is the key element that makes this transfer of the acetyl groups possible.
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Oxygen Esters Stabilized by Resonance Structures
Acyl CoA is similar to acetyl CoA except that it can have other things attached to the carbon. Acetyl CoA just has a {methyl} group attached to the carbon making an acetyl group. And this bond, if it were an oxygen would be an ester bond, which is fairly stable because it can create these resonance structures as seen in the middle. But you cannot do the resonance structures with the sulfur, so this sulfur bond is less stable, and therefore higher energy.
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Table 15.2 Some Activated Carriers in Metabolism
Here's just a brief list of some activated carriers in metabolism. And you can see familiar ATP, NADH, NADPH, FADH, coenzyme A. In addition to those you can see several others that we will talk about (some of these), but we'll talk about them in detail when we get to them. And at the very bottom, nucleoside triphosphates. That would be your nucleosides - adenine, guanine, cytosine, and {thymine} - and also uracil. Where you have adenine there's ATP. So for guanine there's GTP. And for {thymine} there's TTP. And for cytosine there's CTP. And UTP for uracil. So they all have triphosphate forms and these triphosphate forms are used for different purposes.
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Section 15.6 Metabolic Processes Are Regulated in Three Principal Ways The Amounts of Enzymes Are Controlled
The quantity of enzyme present can be regulated at the level of gene transcription.
So there are three main ways that you can control the metabolic processes. And all of these metabolic processes are catalyzed by enzymes, so one way of controlling the processes is by controlling the amount of these enzymes that are present. And that can be done by regulating gene transcription in the nucleus. If you need more of an enzyme then you can transcribe that gene more often and therefore produce more of that enzyme.
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Catalytic Activity Is Regulated
Catalytic activity is regulated allosterically or by reversible covalent modification.
Hormones coordinate metabolic activity, often by instigating the covalent modification of allosteric enzymes.
But one of the most common methods of regulating catalytic activity of enzymes is through allosteric or covalent modification. So signal molecules can attach to these enzymes and cause them to change their behavior.
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The Accessibility of Substrates Is Regulated
Opposing reactions such as fatty acid synthesis and degradation may occur in different cellular compartments.
Regulating the flux of substrates between compartments is used to regulate metabolism.
And the third way of regulating the metabolic processes is by keeping them separate. If you have different compartments in the cell such as the endoplasmic reticulum, or the mitochondrion, then you can carry out certain reactions in these separate compartments. And that's an important way of controlling what's going on.
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