Cellular energy production consists of three processes: photosynthesis, glycolysis and cellular respiration. Glycolysis is not included in cellular respiration for two reasons. 1) While cellular respiration requires oxygen, glycolysis is an anaerobic process, requiring no oxygen. 2) Glycolysis occurs in the cytoplasm, the cell's interior soup, while cellular respiration occurs inside mitochondria, one of the cell's organelles.
Glycolysis supplies fuel (pyruvate), bioenergy (ATP), and an electron-charged biomolecule (NAD+) for cellular respiration. However, glycolysis evolved a billion years before cellular respiration came upon the scene. How was glycolysis able to anticipate these future needs? Random molecular collisions? Intelligent design?
While photosynthesis and glycolysis require external energy, the chemical reactions of cellular respiration are all downhill. Rather than external energy, oxygen’s greed for electrons drives cellular respiration. Rather than an uncontrolled oxidation process (a campfire), the cell extracts energy from a glucose molecule in a series of carefully orchestrated controlled burns. As the driver, oxygen is an essential ingredient in cellular respiration. Where does it come from?
Oxygen is a byproduct of hydrolysis (the splitting of a water molecule) which occurs in the most recent form of photosynthesis. The earliest form relied upon hydrogen as an electron donor rather than water. After bacteria shifted from hydrogen to water, oxygen began accumulating in our early atmosphere. After the oxygen concentration became high enough, a certain type of bacteria began employing oxidation to extract more energy from glucose. This new energy-generating process (cellular respiration) charged 32 ATP molecules, a 16-fold increase in cellular biocurrency.
While the meager return (2 ATP) from glycolysis was enough to power most bacteria, nucleated cells (eukaryotes) require the higher energy payoff supplied by cellular respiration to even exist. How were high-energy bacteria able to evolve into eukaryotic cells, such as the 70 billion cells in our body?
According to the current model, a larger prokaryote (an archaeon) swallowed one of these high-energy bacteria. Over the next billion years, genetic mutation resulted in a mutual dependency between the two prokaryotes. Evolutionary forces then relied upon the extra energy to produce larger cells containing a nucleus and an organelle derived from the swallowed bacterium. Called eukaryotes, these high energy, nucleated cells eventually joined together to become multicellular organisms, such as us.
This new energy strategy, i.e. cellular respiration, consists of three distinct stages. The Krebs cycle (the first stage) is fueled by the byproduct of glycolysis (pyruvate). While charging only 2 more ATP molecules, the Krebs cycle passes electrons and protons to transport molecules that power chemiosmosis, the final stage where the enormous energy payoff occurs. In the second stage, electrons push protons across a membrane to establish an energy gradient. When a threshold is passed, a door opens and the protons rush across a barrier, spinning a molecular turnstile (ATP synthase), which charges 30 ATP molecules, enough to power multicellular being like us.
The cell is incredibly efficient in its use of materials. The three byproducts of the cellular respiration are: 36 charged ATP molecules (cellular energy currency), 10 loaded transport molecules (which are recycled) and 6 carbon dioxide molecules (the only waste product).
Although given off as waste, carbon dioxide is an essential ingredient in the cell’s energy-producing biocycle. After entering the atmosphere and becoming part of the air we breathe, photosynthesis captures the carbon from this molecule to create the extraordinary biomolecule (G3P) that is the fuel for glycolysis and cellular respiration. This final process releases carbon dioxide into the atmosphere. And the carbon biocycle begins anew. In such a way, the cell uses every atom in its energy production cycle.
Ancient Glycolysis supplies Fuel & Electron Carrier for Modern Cellular Respiration?
Oxygen’s Greed for Electrons drives Cellular Respiration
Bacteria develop Better Energy Producing System - enabling Us
Krebs Cycle: Paltry Energy Payoff
Miracle of the Electron Transport Chain & Chemiosmosis
Life’s Parsimonious use of Products from Energy Production
In order to produce bioenergy/biomass, cells rely upon biocycles. In the prior cycle we discussed one the cell’s prime biocycles - the Calvin cycle. However, the cell’s energy production itself is an all-encompassing biocycle that includes the Calvin cycle as one of its mini-biocycles. The cell’s energy-producing biocycle consists of three main processes. Prior chapters discussed two of these – photosynthesis and glycolysis. This chapter focuses upon the third process in this biocycle - cellular respiration.
ATP molecules are the storage batteries for our body and every other organism including single cell bacteria – the simplest life form. Glycolysis produces just enough ATP to fuel prokaryotes (cells that don’t have a nucleus, such as bacteria). While sufficient for bacteria, this is not enough fuel to power eukaryotes (the more complex nucleated cells that are the basis of multi-cellular organisms, such as plants and animals). To obtain the necessary amount of charged ATP molecules to satisfy their energy needs, eukaryotes (nucleated cells) require one other meta-process in addition to glycolysis – cellular respiration.
Cellular respiration consists of three more processes. They are in order: 1) the Krebs cycle, 2) the electron transport chain and 3) chemiosmosis. Each process is unique - totally unlike the other.
Before examining these final processes that our cells use to charge ATP molecules, let us first examine why the trio of processes is called cellular respiration and then why glycolysis is not technically part of the group.
Cellular respiration gives off carbon dioxide as a waste product of its chemical reactions. This carbon dioxide is why the term respiration is applied to the entire process.
Supplying the fuel (pyruvate) for cellular respiration, glycolysis is an essential stage in cellular energy production. However, this ancient process is not included as a stage in cellular respiration for at least two reasons.
Glycolysis is an anaerobic process, as it doesn’t require oxygen. As one of the earliest energy producing methods, this property was crucial, as oxygen was not readily available in Earth’s original atmosphere. It was only with the advent of photosynthesis that our planet’s atmosphere became oxygen rich.
Besides being anaerobic, glycolysis, as a primitive energy source for all living systems, occurs within the cell’s cytoplasm. The 10 enzymes required to catalyze the 10 steps of the glycolytic process are free-floating in this interior soup. In contrast, cellular respiration occurs inside special organelles called mitochondria. The enzymes required to catalyze the more complex processes of cellular respiration are tightly bound in ordered fashion in the organelle’s membrane. This physical separation alone justifies the exclusion of glycolysis from cellular respiration.
Every cell continues to employ the relative simplicity of anaerobic glycolysis to supply a small amount of energy. In addition to this energy, eukaryotic cells and some single celled prokaryotes take advantage of the waste products of glycolysis. The end-product (pyruvate) supplies the fuel for the major energy producer - cellular respiration (CR). What an incredible coincidence! Glycolysis just happened to have a useful energy-rich molecule as an end-product.
Perhaps more amazing, this primitive energy producing method also places an electron in a NAD molecule. This special molecule transports this electron from outside to inside the mitochondria. Here in this new location the electron’s energy is a key component in chemiosmosis, the final stage of cellular respiration.
As cellular respiration didn’t exist in the early days, how did the bacterium know to charge this molecule for future use a billion years later? And who was responsible for the intelligent design and construction of the first NAD molecule? What ancient research team and factory designed and synthesized these functionally perfect objects? And who assembled the electron transport chain? Aliens? Truly miraculous!
If this were the end of the story, it would be pretty boring - interesting but without drama. However, the relationship between these two distinct processes is actually quite exciting as it led to multi-cellular organisms, such as ourselves.
Glycolysis is a cellular universal, as it doesn’t require any atmospheric gases to run. It only needs a few ATP molecules to push its initial chemical transformations uphill and then a string of 10 enzymes to bring these reactions up to the speed of Life. These enzymes are just floating around the cytoplasm of the cell waiting for the call. While certainly requiring biochemicals, glycolysis does not need any environmental assistance.
As such, the energy creating process is independent of environment. It can operate almost anywhere. Due to this versatility, glycolysis was one of the first metabolic pathways that Life employed to recharge ATP molecules – to create useful bioenergy.
In contrast, cellular respiration was a latecomer to the game. It requires oxygen to operate. Oxygen drives the process – pulling the many chemical reactions along. Due to this dependency, cellular respiration could only evolve after there was sufficient oxygen in the atmosphere or the ocean. Where did the oxygen come from?
As we saw in a previous section, oxygen is a byproduct of cyanobacteria-originated photosynthesis. Recall that this form of photosynthesis grabs a carbon atom from a carbon dioxide molecule to produce 6-carbon glucose. In so doing, the reaction releases oxygen from molecular bondage with carbon. While carbon is forced to serve the life force, the liberated oxygen is free to soar in the atmosphere, .
However, oxygen is ever greedy for electrons. This greed is what causes fires. With appropriate heat and combustible fuel, epitomized by wood with all its organic, high-energy molecules, the oxygen in the air we breathe strips molecules of their electrons. The oxidation process transforms complex organic materials into inorganic, low energy molecules. Oxygen’s greed for electrons breaks complex mega-molecules into their basic components - simpler molecules like carbon dioxide.
Fire, rust and rot are all oxidation processes. Greedy oxygen steals electrons from neighboring molecules. Loss of electrons frequently results in the molecule’s degradation into a simpler, low energy form – charcoal, fragile metal or stale food.
This destructive capacity is why the oxygenation of our atmosphere is called the ‘oxygen catastrophe’. The increasing amount of atmospheric oxygen destroyed established food chains and anaerobic ecosystems. This destruction of complex living networks that had developed over billions of years ultimately resulted in mass extinctions of the dependent living systems that could not adapt to the new order.
As oxidation degrades complex molecules into a simpler form, energy is given off – frequently heat. All the energy that was stored in the chemical bonds of the complex molecules is released. The scorching heat from a campfire is a good example of this released energy.
Many, if not most, oxidation processes are uncontrolled burns, such as fire, rust and rot. The burst of energy provides some temporary heat, perhaps warmth, that is almost instantly released into the atmosphere. The heat is absorbed and dissipated into the greater volume of the surrounding air. Witness the rapid cooling of a heated home when the door is left open on a frigid winter’s day.
In contrast, the oxidation process associated with cellular respiration is a controlled burn. The cell, or more precisely the cell’s mitochondria is able to extract and store up to 40% of the energy given off when a glucose molecule is oxidized into 6 carbon dioxide molecules.
How does the cell’s energy-producing organelle, the mitochondria achieve this miraculous result?
Rather than allowing oxygen to meet up with glucose immediately – this chance meeting would have unpredictable results – the cell demands an elaborate courtship ritual.
Oxygen’s desire for glucose’s electrons definitely drives the chemical reactions (no external energy required). Indeed oxygen is one of the best electron acceptors. For this reason, aerobic cellular respiration was a huge evolutionary step.
However, the mitochondria will not allow the oxygen to dissipate all the energy in a burst of passion. Rather mitochondria draw off the released energy in a series of controlled burns that are regulated by enzymes (8 enzymes in the Kreb’s cycle alone). The required specificity of the chemical reactions is so high that the enzymes are bound closely together in the mitochondria’s membrane. Contrast this tight enzymatic regulation of cellular respiration with the free-floating enzymes of glycolysis – just hanging out, rather than ordered.
As a latecomer to cellular energy production, when and how did cellular respiration arise? As with every other metabolic pathway, bacteria were the first to develop a more powerful method of generating energy – cellular respiration.
Let us review. All cells via glycolysis employ 2 ATP molecules to generate/charge 4 ATP molecules. Specifically, the energy derived from the controlled breakdown of glucose does the work of adding a phosphate group to an ADP molecule. This doubling of the initial investment provided(s) enough usable energy to power the life force of prokaryotes, i.e. single cells without a nucleus, e.g. bacteria, for billions of years. Still does.
However, for eukaryotes, i.e. cells with a nucleus, 2 additional ATP molecules per glucose molecule is simply not enough energy to power the more complex functions associated with their metabolic pathways and organelles. Eukaryotes are significant as the building blocks of multi-cellular organisms, such as yours truly. Bacteria are just simply too independent to join together in these rigid cellular societies.
While there is a net gain of 2 ATP molecules from glycolysis, there is a net gain of between 32 to 34 charged ATP from cellular respiration. This is a huge increase (16-fold) in the amount of discretionary income that the cell has at its disposal from the reduction of one glucose molecule into carbon dioxide.
While bacteria developed the process, eukaryotes, i.e. our type of cells, took it to a new level. Somewhere along the evolutionary pathway, a clever single celled archaea swallowed a bacterium that was employing this new energy-producing method. Trapped inside, the bacteria then began producing energy for the host cell.
Gradually over upwards of a billion years, the two formed a symbiotic relationship. This significant partnership eventually resulted in cells with a nucleus combined with organelles, i.e. eukaryotes. This evolutionary surprise ultimately gave rise to multicellular organisms and finally us. While never sharing the same DNA, the inner and outer cells provided each other with complementary services. The inner, an organelle named mitochondria, supply an abundant amount of energy to the outer, while the outer supplies nutrients et al to the inner.
Evolution: Prokaryotes > Eukaryotes > Multi-cellular > Us
Maintaining his integrity, the inner being keeps his secrets hidden within his permeable membrane that separates him from his host or jailor, depending upon perspective. The host continues to employ glycolysis to produce a paltry net benefit of 2 ATP molecules. In order to take advantage of the trapped bacterium’s talents, the host supplies his servant cell with fuel. Conveniently, the fuel for cellular respiration is the end product of glycolysis – 2 three carbon molecules – pyruvate by name. Derived from the splitting of glucose (glycolysis), these special biomolecules still have plenty of energy stored within their chemical bonds.
How did our mitochondria, now a servant, previously an independent operator, tap into the latent energy in a glucose molecule? What techniques had his ancestors acquired that allowed them to transform the energy stored in pyruvate’s chemical bonds into a useable, discretionary biological energy source? What are the mitochondria’s proprietary secrets?
There are 3 stages to this alchemical process. As a group, they are called cellular respiration. It is an aerobic process, as oxygen drives the chemical reactions and carbon dioxide is the end result. Further the entire process occurs within the mitochondria.
Now we are inside the mitochondria, an organelle inside the cell, along with some extraordinary molecules (pyruvate and NAD) that have been produced by hydrolysis. The stage has been set for the energy production system that enables the very existence of us and every other organism, e.g. plant, animal or mycelium – cellular respiration.
Cellular respiration consists of three unique stages – each with individual steps: 1) the Krebs cycle, 2) the electron transport chain and 3) chemiosmosis. The 8 steps of the first stage (the Krebs cycle) carefully extracts energy from pyruvate, the end-product of glycolysis. Rather than recklessly burning through the energy, this unique stage utilizes the remaining energy in a variety of ways.
The Krebs cycle does charge a few more ATP molecules. However, the real energy payoff comes in the final stage, chemiosmosis, also called phosphorylation. The primary importance of the Krebs cycle and the electron transport chain is setting up the necessary conditions for the final stage which can yield up to 32 ATP molecules. Now that is significant!
As an endless loop and one of the cell’s primary biocycles, the Krebs cycle is amazing in and of itself. The end product initiates the next cycle. Neither beginning, nor end. No cause-effect. No hierarchy. Not wanting to violate the conservation of energy, the cycle does require the addition of some outside help. Without a beginning, how and where was the cycle initiated? Indeed the cyclical nature impeded its discovery.
Other than its astonishing cyclical nature, the Krebs cycle is fairly traditional. It employs the same basic method as glycolysis – enzyme coupling – to produce bio-energy. A phosphate chain is added to an ADP molecule via the energy released when an enzyme catalyzes a chemical reaction. However, this ancient procedure only produces a few ATP molecules – and just one at a time – not nearly sufficient for the growing energy demands of Life’s evolving family.
We can imagine the early bacterial scientists and engineers being a mite frustrated with this paltry reward from their ingenious cyclical process. They needed something even more imaginative to tap into all that energy stored in the chemical bonds of pyruvate. They needed a paradigm shift. What the new breed of bacteria came up with was and is mindboggling!
In addition to charging ATP molecules, both glycolysis and the Krebs cycle also charge some special molecules by simply adding an electron and a proton. With the addition of these fundamental subatomic particles, NAD+ becomes NADH and FAD becomes FADH2. The most important feature of these molecules is that the electrons lose relatively little energy in the transfer. Plus these electrons represent a considerable amount of energy that can be harnessed by the cell. However, this stored energy is not in a form that is readily useable by the cell1.
This is where the electron transport chain comes in. The two charged molecules first transport the electrons they were given in these other processes to another location. The stored potential energy in the electron is then used to do work. These exceptional molecules employ their extra electron to push a proton across a membrane.
Once the positive charge from these accumulating protons passes a threshold, they rush through a molecular turn-style – like fans at a soccer match – impelled by diffusion (entropy). The tremendous enthusiasm of the protons spins the turn-style, i.e. ATP Synthase, so fast that it charges 32 ATP molecules. Compared with the one-by-one enzymatic approach, this is an enormous yield! This is a great example of the sophisticated metabolic strategy that is the specialty of every cell – ‘the alternation energy and entropy’.
The molecules of the electron transport chain and ATP have a symmetric logic. Just as ATP is responsible for the orderly transfer of energy in the cell, NAD and FAD are responsible for the orderly transfer of electrons and protons. The random collisions of inanimate matter, while sufficient for the creation of enormous galaxies, are simply not enough to ensure the survival of a single microscopic cell.
Wow! Cells employ photons, electrons and protons, the fundamental building blocks of atoms to produce useable energy. I must bow before the Marvel. In addition to bulky elements like oxygen and carbon, cells use these three fundamental particles to generate and store bioenergy and create biosubstance. Whoa!
The energy from a single photon is captured in a chloroplast’s photo system. The photon’s energy excites an electron. After being transported by special molecules to another location, the energized electron pushes some protons across a membrane. In their rush to get back across the membrane, they charge enough ATP molecules to enable multi-cellular life. Wow again!
Each of our Cells employ:
Photons, Electrons & Protons to create & store Bioenergy & Biomass
Hallelujah! Praise be to whoever is responsible for this Divine Mystery.
Let’s summarize the cell’s energy producing processes and products in some equation-like statements.
Glycolysis > 2ATP + 2NADH
Krebs > 2ATP + 8NADH + 2FADH2 + 6CO2
Chemiosmosis > 32ATP
Summing up the molecular products of the 3 stages: 36 ATP, 10 NADH, 2 FADH2 and 6 CO2. Let us examine the fate of each of these molecules. Foreshadowing, recall that the cell is exceptionally parsimonious in its use of atoms.
Cellular respiration et al carefully, methodically, step-by-step extracts the potential energy stored in a single glucose molecule to power 36 ATP molecules. Put another way, cells digest glucose – transforming it into a usable form. Cells can then readily employ this ‘digested’ potential energy to do work, e.g. push reactions uphill, as in glycolysis or contract muscles.
While ATP molecules are the primary product, the transport molecules (10NADH + 2 FADH2)are essential to the cellular energy production process. Infused with potential energy during glycolysis and the Krebs cycle, these special biomolecules give up their energy to fuel chemiosmosis. Recall that nucleated cells such as ours require the enormous energy payoff from chemiosmosis to survive.
As with ATP molecules, these electron transport molecules are not lost, but rather are recharged for use over and over and over again. Rather than created or wasted, these biomolecules merely alternate between forms – from charged with potential bioenergy to inert. While biochemists have different symbols to differentiate between the 2 states, the underlying structure never changes. In similar fashion, a cell phone looks the same whether charged or dead. Yet we all know there is world of difference between the two states – operable or not. Neither created nor wasted, these products of cellular respiration are more akin to storage batteries that are regularly recharged for use over and over again.
The only other product, carbon dioxide (6CO2), is considered to be a waste product, as it is released into the atmosphere. However, it is hardly trash. Freed from bondage during the Krebs cycle, carbon dioxide becomes part of the air we breathe. As such, it is readily available to all creatures that live on land, e.g. plants and animals.
Plants suck up the carbon dioxide as one of the necessary ingredients in photosynthesis. Plants extract carbon atoms from carbon dioxide to create biomass and bioenergy. The biomass becomes the substance of Life – the flesh of our bodies and the wood of trees.
Summarizing, there are three products from the metabolic processes that the cell employs to extract the energy from a glucose molecule, ATP molecules, electron transport molecules, and carbon dioxide. The process stores the energy extracted from the glucose in ATP molecules for use at a future time. The transport molecules simply move electrons and protons to where they are needed. Like ATP, these transport molecules are recycled. Rather than used up, they alternate between charged and not. As their name implies, they are akin to a bus that carries passengers from place to place, while never losing its basic structure.
Carbon dioxide is the only product that leaves the system. However, released into atmosphere, it becomes part of the air we breathe and then an essential ingredient of photosynthesis. This process transforms this inorganic molecule into an organic biomolecule. Plants require the carbon atom to create the glucose that becomes the fuel for glycolysis and cellular respiration. In such a way, the cell employs all the atoms in its energy production cycle.
So this leads us to the cell’s mega-biocycle.
The cell employs bioenergy in many ways. One crucial use is synthesizing the cell’s super-complex, high energy biomolecules, such as glucose. Many of these biomolecules include the carbon atom from carbon dioxide that is released into the atmosphere during the Krebs cycle. Some estimates have it that living systems contain over ten million different carbon compounds.
The cell employs ATP molecules to synthesize not just any old configuration, but rather a carbon ring for many of these biomolecules. These super biomolecules that include carbon rings are incredibly complex. Biochemists have devoted an entire field to these special compounds. Called organic chemistry, it is defined as the study of the carbon-based molecules. Actually, organic refers to Life, so it is the chemistry of Life.
So we have another endless biocycle – the carbon cycle. The waste product of cellular respiration (carbon dioxide) is an essential ingredient for photosynthesis. Photosynthesis employs solar energy to convert the waste product of cellular respiration into biomass-energy. Cellular respiration then extracts bioenergy from the end-product of photosynthesis and generates a waste product that photosynthesis employs to generate biomass-energy.
High-energy organic molecules (glucose) become the fuel for cellular respiration, which releases carbon as a waste product, which is transformed into glucose molecules, which are the fuel of cellular respiration. From low energy, inorganic carbon dioxide molecules to high energy, organic (carbon-containing) molecules, and then back again. The end/waste product of one becomes the fuel for the other – over and over and over again.
Low Energy Carbon Dioxide = Waste Product of Cellular Respiration
Low Energy Carbon Dioxide = Fuel of Photosynthesis
High Energy Glucose = End Product of Photosynthesis
High Energy Glucose = Fuel of Cellular Respiration
This carbon-based cycle is holistic. The cyclic processes only make sense when considering the whole organism. The transformation of an inorganic carbon molecule into an organic biomolecule and then back again serves cellular needs. The conversion of solar energy into bioenergy only has meaning to the cell.
Further the processes in the carbon cycle follow one another in a regular and timely fashion. Rather than relying upon the unpredictable random collisions of inanimate molecules, the stages must occur one after another in a specific, timely, ordered sequence.
It is evident that the carbon biocycle, indeed all biocycles, belongs to a holistic system that includes a temporal sense. The product of the carbon biocycle (stored bioenergy) supports a holistic life force over time. As it always reacts immediately to stimuli, Matter has neither of these features. In contrast, a holistic and temporal sense are fundamental features of Life’s Information Digestion system.
1 Great Courses, Lectures in Biology, p. 272