Energy’S UP: Instalment Four. The Mystery of ATP

Friday, August 18, 12023 Human Era (HE)

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1. Continuation Explanation
2. The Mystery of ATP
   1. What Exactly is ATP?
   2. Why ATP
   3. What’s So Special About ATP?
   4. ATP Accounting Annotations
3. Life’s Currency Exchange: Free Energy Sources
4. As a Matter of Fact. And a Simple Question.
   1. A Complicating Asterisk
      1. Corn Maze
      2. Those Damn Hormones
   2. Stardust is Some Strange Shit: A Hint
      1. Contributing to the Carbon Cycle
         1. You Are What You Eat.
5. What About Storage and Access?
   1. Curious Carbohydrates
      1. Specific to Storage
      2. Trade and Transport
      3. Dissing Dietary Carbs
   2. Fabulous Fats
      1. Fat Transport
      2. Fat Store
      3. Dietary Fat Bashing
   3. Preposterous Proteins
      1. Transporting Proteins
      2. Limited True Storage
      3. Pro Protein Propaganda
6. What’s the Difference?
   1. Chemistry: Structure Governs Function
      1. Carbohydrates Versus Fats: Organization of Organics
   2. Physiology: Function Takes Form
      1. A False Dichotomy
7. When someone gains weight, where does the fat come from?
   1. Powered by Plants
8. Addendum

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Continuation Explanation

This post is a continuation of a series on energy and its relationship to stand up paddleboarding (SUP). The impetus for the post came after a conversation with a client on energy systems. We got into some fairly intricate details and I realized that a refresher for myself was in order. I found that writing a few posts on anatomy and biomechanics specific to SUP served as a great review of my anatomical knowledge, and I thought it would be a fun exercise to refresh on some energy metabolism physiology.

The first instalment covered some background basics before branching into a rant on the semantics and sex-typing, and it ended by attempting to define what energy is. The second instalment looked at work, enthalpy and free energy, and carbon as the building block of life. The third instalment focused on photosynthesis, chemical bonds, and the semantics of systems and states. This post continues from where we left off and covers adenosine triphosphate (ATP, the energy currency of biology), macronutrients and their utilization and storage, and the mystery of where fat goes when you lose weight. Allons-y avec ATP.

The Mystery of ATP

Life is work. Both in the physical and metaphysical sense. Cells require energy to perform their daily maintenance tasks.  For example, body movement and/or the synthesis of macromolecules. Chemical equilibria and the direction of energetically favourable reactions are determined by the laws of thermodynamics.

As mentioned in instalment two, Gibbs free energy is the fundamental thermodynamic quantity that regulates the energetics of biochemical reactions. By considering both changes in enthalpy and entropy, the alteration in free energy allows us to foresee the energetic feasibility of a reaction. Consequently, chemical reactions naturally occur in the direction that favours lower energy, leading to a decrease in free energy.

Many of the intracellular reactions required to maintain cellular function are energetically unfavourable. They can only occur at the expense of additional energy input. Energetically unfavourable reactions must be coupled with energetically favourable reactions in order to proceed. Evolution’s solution was the constitution of ATP. The ‘high-energy’ phosphate bonds in ATP allow energy to be stored and transferred within the cell. Energy-yielding reactions within the cell are coupled to ATP synthesis, and energy-requiring reactions are coupled to ATP hydrolysis to take advantage of Gibbs free energy exchanges.

What Exactly is ATP?

Adenosine triphosphate is an organic compound, and structurally, it is a nucleoside triphosphate. This means it is comprised of a nitrogenous base (adenine), a ribose sugar, and three serially bonded phosphate groups. The purine nucleobase of ATP, adenine, may sound familiar since it is of deoxyribonucleic acid (DNA) fame. It is one of the four nucleobases in the nucleic acids of DNA. The other three are guanine (G), cytosine (C), and thymine (T). Adenosine triphosphate appears to be an ancient atomic structure that arose as an antiphon to animation’s activity accounting adversities.

Chemical structure of Adenosine Triphosphate (ATP).
Image Source: https://en.wikipedia.org/wiki/Adenosine_triphosphate

Cells take advantage of the properties of ATP to drive the many energetically unfavourable reactions that must take place in biological systems. Adenosine triphosphate plays a crucial role in this process by serving as a reservoir of free energy within the cell.

Why ATP

Interestingly, it may be that the primordial origins of the utility of ATP may not stem from its use as an energy carrier (currency), but rather may be related to its ability to prevent proteins from aggregating.

What’s So Special About ATP?

Adenosine triphosphate is somewhat special in that it contains a series of so-called ‘high-energy’ phosphate bonds. There is “nothing special about the chemical bonds themselves” besides their capacity to liberate large amounts of free energy when hydrolyzed. With the help of enzymes (i.e., ATPases) in the presence of water, ATP can hydrolyze into adenosine diphosphate (ADP) and a phosphate ion (P_i). For an explanation of why ATP can store so much potential energy, see this video by Andrey K., “Energy Storage in Chemical Bonds.”

The image below depicts how ATP is synthesized and degraded from ADP with (1) representing an output of energy, and (2) an input. For a more in-depth explanation see this video, “Hydrolysis of ATP,” by Easy Peasy for an account of the physiochemistry of why ATP hydrolysis can release more energy than the activation energy required to break the phosphoanhydride bond. Or just take it at face value that the cleavage of the phosphate group from ATP releases more energy than it takes to separate the bond, resulting in the availability of free energy.

ATP Accounting Annotations

At rest, each muscle cell contains roughly one billion ATP molecules (i.e., 1,000,000,000 little ATPs)! Those billion ATP molecules will all be used and replaced every one to two minutes! To put that into some perspective of how big a billion (and a trillion) looks like in currency, click here. During intense exercise, muscle ATP production can increase 1000-fold to meet the demands of intense muscle contraction. That means our resting one billion two-minute consumption skyrockets to an astounding one trillion ATP molecules biminutely (i.e., 1,000,000,000,000)!

Looked at differently, the total quantity of ATP in an adult is approximately 0.10 mol/L. The average adult requires approximately 100 to 150 mol/L of ATP daily, which means that each ATP molecule is recycled some 1000 to 1500 times per day. Approximately 65 kilograms of ATP are recycled per day in a normal resting adult. You essentially turn over your body weight in ATP daily!

Life’s Currency Exchange: Free Energy Sources

Living organisms obtain their free energy in different ways. Three broad categories can be drawn, organotrophs, lithotrophs, and phototrophs. Organotrophic organisms get their energy by feeding on other living things or the organic chemicals they produce. For example, animals, fungi, and bacteria that live in the human gut are all organotrophic organisms. The other two classifications get their energy by feeding on non-living things. Lithotrophic organisms get their energy by feeding on rock, which is an inorganic substance. And phototrophic organisms feed on sunlight.

Humans are chemo-organo-heterotrophs. We are chemotrophs in that we obtain energy by the oxidation of electron donors from our environment. Organotrophs in that we feed on organic matter for our electrons. And we are heterotrophs since we can not produce our own food and source carbon (C) from plant and animal matter.

As chemoorganoheterotrophs, we can not exist without lithotrophs and phototrophs as primary energy converters. Presently, we rely on phototrophs to harvest the energy of sunlight so that we can then prey on them. But we are indebted to the lithotrophs of history that expedited the liberation of inorganic materials paving the way for later lifeforms. Physics to chemistry to biology.

As a Matter of Fact. And a Simple Question.

Here is an elegantly simple question that, for many, has a surprising answer. When somebody loses weight, where does the fat go? Pause for a moment and think about that. Something has to leave the body. And a word of warning, do not confuse weight with energy, since the latter has been much of the focus of this series of posts. In an excellent paper on the topic, the authors highlight that most people think that fat is converted into heat. But this would violate the conservation of mass. This is true at the macroscopic level. However, things get strange at the quantum level where mass is energy. Or better stated, mass is energy confined to an arbitrary system. In our human world at the macroscopic level, in the context of weight loss, the human body is more of an open system than a closed one, so the mass is lost to the wider environment. So, there is no violation of the conservation of mass law. But in other contexts, mass is energy, so the desire to equate weight loss with the dissipation of heat is not outlandishly off the mark.

Putting the quirks of the quantum world aside, it seems that many professionals and laypeople are unable to explicitly identify where fat goes during weight loss. During my undergraduate degree in Human Kinetics, I don’t think the mass component of the answer was explicitly stated. The trend was to take the calories in/calories out approach and deal with the energy, but as a matter of course, not the matter. The answer was always there in the biochemical equations of cellular respiration, but students needed to make that connection on their own. I suspect now the trend has shifted to explicitly highlight this distinction.

A Complicating Asterisk

As a brief aside, it is worth noting that not everyone subscribes to the calories in/calories out doctrine. At the heart of controversy, perhaps, is the commonly asked question, Are all calories equal? The simple answer to that is yes. By definition, a calorie is “a unit of energy equivalent to the heat energy needed to raise the temperature of 1 gram of water by 1 °C (now often defined as equal to 4.1868 joules).” So, by this definition, all calories are equal. But what the question is trying to get at is whether the consumption of equal caloric values from different sources has the same metabolic effect on the body. And here is where things get slightly more complicated.

Corn Maze

I recall reading Gary Taubes‘ 12011 (HE) book, “Why We Get Fat,” where he argues for endocrinological factors mediating energy availability from the foodstuff we eat. While that certainly plays a role, another factor is that the Atwater factors we use to calculate calories from food mass may not be correct. It turns out that burning food and faeces in a bomb calorimeter to determine the energy content of food doesn’t totally correspond to the energy available from digestion and metabolism in vivo (the so-called sweet corn phenomenon for those who want to read between the lines). Not every you eat gets digested to the point at which it can be burned as fuel by the body. A decent portion of what you eat goes straight through from the hole at one end to the hole at the other (e.g., I’m looking at you corn kernels).

Those Damn Hormones

There seems to be more and more mounting evidence to show that while a calorie is a calorie, a calorie consumed in foodstuff does not always translate to a calorie, energetically speaking, available at the cellular respiration level (for more details check out this interview of Robert Lustig, “Dr. Robert Lustig: How Sugar & Processed Foods Impact Your Health,” on the Huberman Lab podcast).

Stardust is Some Strange Shit: A Hint

One way to come to the answer to the query above is to reverse engineer the problem. When someone gains weight, where does the fat come from? Most of us are acutely aware that if we eat too much, we will gain weight. But again, we run the risk here of equating excess energy with weight gain. Arguably, the two are the same but different at the same time. Perhaps a better question is to consider where we get our foodstuff from, the emphasis on “stuff.” As explained above, we are chemoorganotrophs. We eat plants or animals to get our energy and building materials. Whether carnivore, omnivore, pescatarian, pollotarian, vegetarian, or vegan, the human food web eventually leads back to plants. So, how do plants grow? Photosynthesis! Not only does photosynthesis give plants their energy, it is also where botanicals bag the bulk of their building blocks.

The craziest component of the complex chemistry of the Calvin cycle is that plants gain their mass mainly through carbon capture. The carbohydrates created when collated are collectively called cellulose. By and large, the biggest contributor to a plant’s mass is carbon. Contrary to the commonly suggested source of a tree’s mass increase, i.e., how trees get bigger, as serendipitously springing from the soil, as is shown in the 12012 HE Veritasium video, the actual answer is air. It is worth noting that plants do get their nitrogen (N) as a nutrient from the soil despite the irony that it is the most abundant gas in the atmosphere at approximately 78%. The air around us, specifically carbon dioxide, only makes up approximately 0.04% of air, is taken in by plants, and then used to make their material mass. First, as a six-carbon hexose, a simple sugar (monosaccharide), that is called glucose. Then glucose can be polymerised into the long-chain structure of cellulose, which can be simply thought of as a string or stack of sugar molecules. Cellulose is the main stuff found in plant cell walls and gives them their structure and stiffness. Cellulose is indigestible to humans and functions as dietary fibre, keeping us regular. But some animals and bacteria are able to break it down enough to be able to liberate the energy bound within.

Contributing to the Carbon Cycle

We are all loosely aware of the fact that plants are carbon-based given the current chatter around climate change. Nearly everyone knows that the burning of wood releases carbon, mainly in the form of carbon dioxide into the atmosphere. Similarly, the fossil fuels we burn regularly are stores of this carbon that were buried away from past periods, e.g., the Devonian and Carboniferous, the former of which is when trees first appeared, and the latter when they were deposited into the many coal beds formed at that time. What we often fail to connect is how the carbon cycle works and how we are a part of it. There is the geological “slow carbon cycle” and the biological “fast carbon cycle.” Not only do we fail to connect the dots between our industrial practices and anthropogenic climate change, but we also miss the connection between more ‘natural’ effects of biology on climate change. We are not the first organisms to disrupt the climate. Cyanobacteria hold the claim to be the original biogenic climate change catalyst. Around 2.4 – 2.1 billion years ago cyanobacteria that developed the ability to do photosynthesis and release oxygen (O) into the environment some 300 million years earlier caused the Great Oxygenation Event, possibly wiping out large swathes of anaerobic organisms and likely causing the period known as Snowball Earth. Today we not only affect the climate through our industrial decisions, but we also continue to contribute to the carbon cycle as the offspring of lifeforms that were able to resist the poison of increasing oxygen levels and survive via aerobic metabolism.

You Are What You Eat.

Many people are familiar with the fact that the human body is made up mostly of water, as much as 60% by weight. A division less commonly known or considered is the elemental makeup of the human body. The human body is composed of around 20 different elements. However, approximately 96% of the mass of the human body is made up of just four elements: oxygen, carbon, hydrogen (H), and nitrogen. Not surprisingly, oxygen is the most abundant element in the body by mass given the water composition of the body and the relative size of oxygen versus hydrogen. Carbon is the next most abundant element in the body. By number, hydrogen is the most common atom in the body.

The addition of two more elements to the calculus, calcium and phosphorus, accounts for nearly 99% of the body’s mass with a total of just six elements. Five other elements: potassium, sulphur, sodium, chlorine, and magnesium makeup, another approximately 0.85%. The remaining balance, around 0.15%, is made up of other trace elements.

We get these elements through our diet, and along with the chemicals we consume comes the energy that connects them together. It is the breaking and reconstituting of these bond systems that allows us to liberate the stored energy of the Sun and power our metabolism. But we depend on the macronutrients we consume to provide us with the building blocks for our bodies. The age-old adage you are what you eat is a truism.

For a great listen on this topic, check out the BBC‘s Infinite Monkey Cage episode “Are we what we eat?“

What About Storage and Access?

Carbohydrates, fats, and proteins are the source of stores of energy and building materials, but they are cumbersome to use. Your body breaks down the macronutrients into their constituent building blocks in order to transport and utilize them.

Curious Carbohydrates

Carbohydrates are a class of biomolecules, that are organic compounds consisting of carbon, hydrogen and oxygen atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (e.g., water). Carbohydrates come in a complete array of category classes. But simply, they can be conceived of as a carbon atom attached to a water molecule, that is, carbon hydrates. Typically, carbohydrates have the empirical formula C_m(H₂O)_n, where the m value may or may not be different from the n value.

Carbohydrates are broken down into glucose and can be stored as glycogen in many cells, but the bulk of glycogen is stored in muscle and liver cells. Glycogen is like the animal equivalent of plant sugar storage that we saw above, i.e., cellulose. Just as we conceptualized collections of collated carbohydrates (i.e., sugars) in plants as cellulose, glycogen can be conceived of as stacks of glucose molecules in animals.

Specific to Storage

The burdensome side of carbohydrate storage is weight. Every gram of glycogen stored requires at least three grams of water, making it costly to carry as storage in large amounts. Even with this portly property, an average adult human has enough glycogen stored for about a day’s worth of normal activity.

Trade and Transport

Cellular stores of glycogen can be converted to glucose, which is the carbohydrate form that is primarily transported through the blood as blood glucose or sugar. As we will see in installment five, another pertinent form of close to carbohydrate compound is lactate. Despite not technically being a carbohydrate, lactate is an anion by-product of the breakdown of glucose (i.e., glycolysis), that is now recognized as a transferrable form of metabolic substrate in the body via the various lactate shuttles. The chemical formula for lactate is C₃H₅O₃^–, which is essentially a halved glucose molecule (C₆H₁₂O₆) minus a hydrogen, i.e., a proton.

Dissing Dietary Carbs

Despite the bad rap of carbohydrates in popular dietary lore (i.e., carb bashing), when consumed in their less processed and refined form, they can be part of a balanced and nutritious diet. A true critique of carbs needs to consider both the quantity and quality of consumption. Humans can endogenously synthesize carbohydrates, so they technically are not an essential nutrient. Although, the jury is out on how reduced carbohydrate diets affect dietary fibre intake and overall health.

Fabulous Fats

Fats are a subgroup of lipids commonly called triglycerides (or triacylglycerols). Like carbohydrates, they are organic compounds comprised of carbon, hydrogen, and oxygen, with the additional inclusion of nitrogen and sulphur (S). Lipids are a broad group of organic compounds that include fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, and other molecules. Triacylglycerols are the main former of fat in the human body. Triacylglycerols are an ester derived from glycerol and three fatty acids.

If you picture a triacylglycerol as an “E,” then you can conceptualize the vertical line as the three-carbon chain backbone of glycerol and the three horizontal lines representing the free fatty acid chains (obviously, it is not so simply structured but it serves as a simple mental heuristic; see below or click here for three-dimensional model). The fatty acid chains are carboxylic acids with an aliphatic chain, i.e., a string of carbons and hydrogens. Depending on how many hydrogens each carbon atom is attached to, the chain can either be saturated or unsaturated, which in turn governs the structure and properties of the fat.

Fat Transport

Fats must be transported as lipoproteins since fat and water (or blood) don’t mix and too high concentrations of free fatty acids in the blood can be harmful (i.e., cause lipotoxicity and insulin resistance). Thankfully, lipotoxicity can be avoided by detoxification of free fatty acids by their three-fold esterification (i.e., reconstitution) to the trivalent alcohol glycerol to form triacylglycerols (a.k.a. triglycerides) again.

Fat Store

Fats are an efficient store of energy as they are calorically dense. Fats have about nine calories per gram, whereas proteins and carbohydrates have just four calories per gram (this is based on the Atwater factors mentioned, so bear in mind those calories when consumed may not translate into energy available for cellular respiration, but it is a close estimate). Fats can be stored with minimal water, reducing their storage weight by approximately six-fold compared to the same energy equivalent of glycogen. So our waistlines and scales can thank the biochemistry of fat for its efficiency. An average adult human has enough fat stored for about one month’s worth of normal daily activity. In order to be transported into the cell, fats (a.k.a. triacylglycerols or triglycerides) are broken down into glycerol and free fatty acids.

Dietary Fat Bashing

Similar to carbohydrates, fats underwent a negative propaganda campaign. Essentially, the sugar industry funded a smear campaign against fat to cover up the problems with the consumption of simple sugars. It is worth explicitly stating that dietary fats are essential nutrients. Your body needs fats to function. But like many things in life, too much of anything can kill you.

Preposterous Proteins

Proteins are large biomolecules (i.e., macromolecules) that comprise one or more long chains of amino acid residues. Amino acid molecules have a carboxylic acid group and an amine group that are each attached to a carbon atom called the alpha (α) carbon. Each amino acids has a specific side chain, known as an R group (or substituent), that is also attached to the α carbon. The R groups have a variety of shapes, sizes, charges, and reactivities giving the amino acid its characteristics. In turn, the specific protein type is determined by the array of the amino acid sequence. Proteins perform a vast array of functions within organisms.

Transporting Proteins

The constituent components of proteins are amino acids. In order to be transported in the blood, proteins must be broken down into amino acids. They can then travel in the blood as free amino acids or bound to carrier proteins.

There are hundreds of different amino acids in nature, with only about 20 of these being used to create the proteins of the human body. Proteins are so essential to biological function that they are mostly put directly to use postprandially in a sort of amino acid recycling system.

Limited True Storage

However, unlike carbohydrates and fat, proteins are not stored in the body to any substantial degree. That is, amino acids, apart from their active functional state as assembled proteins (e.g., muscle) are not accumulated in an archive. Though, that is not to say that carbohydrates and fats in their stored state are non-functional, far from it.

Proteins are often too big and heavy for efficient transport and storage. For example, muscle, the closest thing to a storage form of protein, is nearly 80% water. In 100 grams of 95% lean ground beef, there are just 21 grams of protein. Amino acids are also relatively reactive and, in excess, are oxidized. Furthermore, there are so many different amino acids in the human body that storage would require a retinue of specialized cells for selective storage.

Pro Protein Propaganda

There appear to be fewer negative popular views of protein. If anything, presently, we are in the process of a protein propaganda push to consume more protein products, perhaps even more than necessary for most people. In any case, protein consumption is non-negotiable, as a subset of amino acids are essential since they can only be obtained via dietary consumption.

What’s the Difference?

Chemistry: Structure Governs Function

As described above, the secret sauce of amino acids is that they are organic compounds that contain both amino and carboxylic acid functional groups. The amino group contains nitrogen. Generally speaking, carbohydrates and fats do not contain nitrogen (but they can, e.g., glucosamine, which is classified as a carbohydrate). The increased chemical diversity of amino acids beyond carbon, hydrogen, and oxygen gives them unique characteristics. When connected together in chains, the 20-plus amino acids can be organized in a variety of patterns, giving rise to 20,000 to over 100,000 proteins in a single human cell.

The other superpower of amino acids is that when they polymerize into proteins, they fold due to the “hydrophobic effect and conventional hydrogen bonding, along with Coulombic interactions and van der Waals interactions.” This gives rise to unique shapes that dictate their function. The most commonly known example of this concept is the lock-and-key model. Remember this from high school biology? In this model, enzyme-substrate complexes are created when complementary geometric contours come together. While this concept is generally true, it fails to consider the complete view of the changeable constitution of proteins. As this video from SubAnima, “How NOT To Think About Cells,” explains, the complete view of proteins is more complex. While we tend to conceptualize proteins as rigid and static, the reality is that they are much more malleable and dynamic. Thus, a more nuanced and complete view of the lock-and-key model is that the enzyme-substrate complex is much more malleable than previously believed. This level of added complexity explains the ability of proteins to work at multiple receptors and under a myriad of physiological conditions.

The nitrogen of amino acids is a defining characteristic, and it is nitrogen balance that determines amino acid metabolism. Amino acids can have several fates in the human body. During amino acid synthesis, the nitrogen remains on the molecule and is incorporated into a polypeptide or protein. During transamination, the amino group is transferred to another carbon skeleton to form a new amino acid. And, during deamination, the amino group is removed from the amino acid and converted into ammonia. Ammonia is toxic to humans and must be excreted, so it is converted to urea or uric acid and excreted via various routes. The remaining carbon skeleton is recycled or oxidized to release energy.

Carbohydrates Versus Fats: Organization of Organics

Carbohydrates and fats are organic compounds, like proteins. Proteins are in a class of their own due to their unique functional groups. So what mainly differentiates fats from carbs? The answer, of course, is their chemical composition.

As stated, carbohydrates are hydrates of carbon. More simply stated, they are carbons with water attached. Thus, the general formula for carbohydrates is C_x(H₂O)_y. But there is a wide array of additional complexities that can arise from this chemistry, collectively called saccharides (from the Ancient Greek σάκχαρον (sákkharon) meaning ‘sugar’). The group includes sugars, starch, and cellulose. Saccharides can be divided into four chemical groups: monosaccharides, disaccharides, oligosaccharides, and polysaccharides.

Lipids (or fats) have a more diverse chemistry (as we saw above). In 11960 HE, Hirsch and colleagues published data that yielded an “average fatty acid” with the formula C_17.4H_33.1O₂. Despite now being over 60 years old, their result remain in remarkable agreement with more recent data. Three “average fatty acids” esterified to the glycerol backbone (i.e., +3C, +6H) give an “average triacylglycerol” with the formula C_54.8H_104.4O₆ (i.e., 3 × (C_17.4H_33.1O₂) + 3C + 6H).

In addition, generally, lipids have a polar, or hydrophilic region (that attracts water), and a substantial non-polar, or hydrophobic, hydrocarbon region (that repels water). This property makes lipids insoluble in water, and that is why fats form globules in water. Fats clump together to prevent the hydrocarbon region from interacting with water.

For a full run-down on the differences between carbohydrates and lipids, check out this article, “Difference Between Carbohydrates and Lipids,” from geeksforgeeks.org.

Physiology: Function Takes Form

As mentioned above, amino acids are not really stored in the body. There are no official protein reserves for use as fuel. Amino acids are put in to function as proteins to build, maintain, and repair body tissues, as well as to synthesize important enzymes and hormones. Under specific conditions, proteins can be degraded and mobilized en masse, but under adequate nutrition, net protein synthesis occurs. From an energy metabolism perspective, under normal circumstances, protein only accounts for approximately five percent of the body’s energy needs. In situations of inadequate nutrition or prolonged endurance-exercise protein in the form of skeletal muscles is broken down to be used as fuel. When glycogen stores are depleted during prolonged intense physical exertion, the body can degrade protein from skeletal muscles into amino acids and convert that into glucose to supply as much as 15 percent of the body’s energy needs.

Carbohydrates in their simple form (e.g., sugar, glucose, fructose, etc.) are the main source of immediate energy. They are quick and easy to metabolize since the body requires less oxygen to burn them. Carbohydrates are often considered the body’s most efficient fuel source. During high-intensity exercise, carbohydrates become the primary fuel source, when the body can not immediately process enough oxygen to meet its energy needs aerobically.

All of our cells can use glucose for energy, but the brain and nervous system are particularly dependent on glucose. Glycogen is a ubiquitous fuel source stored in the cytosol of cells but can also be liberated as glucose for transport in the bloodstream. Glycogen occupies approximately 2% of the volume of cardiac cells, 1%–2% of the volume of skeletal muscle cells, and 5%–6% of the volume of liver cells. In an adult, the liver, which is approximately 1.5 kilograms, can store roughly 100–120 grams of glycogen. The 1–2% of glycogen in skeletal muscle mass translates to roughly 400-500 grams of glycogen in a 70-kilogram adult. Total body glycogen is estimated to be around 600 grams but is dependent on individual factors. Thus, the capacity of your body to store muscle and liver glycogen is limited to approximately 1,800 to 2,000 calories worth of energy. That is enough to fuel 90 to 120 minutes of continuous, vigorous activity or supply the average human with the baseline daily energy requirements, i.e., basal metabolic rate (roughly 1,000-to-1,200 calories for women and 1,200-to-1,600 calories for men).

Despite the body’s need for carbohydrates to fuel the central nervous system, fats are the body’s preferred fuel source at rest and at lower intensities of exertion. Fats are a concentrated source of energy providing more than twice the potential energy of protein and carbohydrate. Lipids are suited for storage since they are insoluble in water. More energy can be stored for less weight compared to their generally hydrophilic macronutrient counterparts of carbohydrates and protein. Some fat is stored in muscle cells, where it can be readily accessible during physical exertion. But fat is mostly stored in the body in the form of triacylglycerols in adipose or fat tissue. Triacylglycerols in adipose tissue must be broken down into fatty acids to be transported through the blood to muscles for fuel. This process is relatively slow compared to the mobilization of carbohydrates for fuel. However, the metabolism of fats at rest, as well as in low- to moderate-intensity physical activity (i.e., at or below 65 percent of aerobic capacity), contributes 50 percent or more of the fuel that muscles need. The percentage decreases as exercise intensity increases. Despite this, the human body has a virtually limitless supply of energy from fat stores. Even in lean individuals, there are over 100,000 calories of energy available from muscle fibre and fat cell stores, enough for over 100 hours of marathon running!

While all the mechanisms behind metabolism are not fully understood, some general conclusions can be drawn. Protein, fat, and carbohydrate all serve as energy sources, but to varying degrees depending on the energy requirement. Fat is the predominant fuel source at rest and workloads below approximately 60% of VO₂max. Somewhere above this ‘threshold’, carbohydrates become the dominant fuel source, and if the duration is sufficient, the relative contribution of proteins will increase from nearly negligible to a meaningful proportion (in the realm of Canadian sales tax rates). Carbohydrates can be quickly metabolized in the absence of oxygen, i.e., anaerobically, but ultimately, all human metabolism is eventually aerobic.

A False Dichotomy

It is worth pointing out that the dichotomy often made between aerobic and anaerobic metabolism is physiologically a false one. While it may serve a purpose for communication and pedagogy, it is not a biological dichotomy. At any given time, metabolism is made up of both aerobic and anaerobic processes. While I would contend that even locally, both processes occur in parallel, systemically, they most certainly cannot operate in isolation. The bioenergetics of metabolism are much more of a spectral or parallel process. As exercise intensity increases, the baseline level of predominantly aerobic metabolism cannot be met by ever increasing aerobic, or mainly oxidative, pathways. Eventually, the contribution to high-intensity exercise is supplemented by larger anaerobic contributions to ATP synthesis. A more accurate depiction of higher-intensity exercise is depicted in the graph on the left below, where increased energy (ATP) demand is met by anaerobic metabolism beyond the theoretical anaerobic threshold.

In contrast, the commonly conceptualized condition on the right where the so-called anaerobic threshold is represented by a cut-off of contributions is incorrect. While I do not dispute the observation that there are changes in metabolism across intensity levels, the classic half-century old contention of an ‘anaerobic threshold‘ no longer fits our current understanding of physiology, as the basic tenant of an anaerobic threshold (i.e., oxygen-limited metabolism) is no longer tenable. However, this observation does not necessarily discount the functional utility of attempting to quantify bioenergetic workload transitions within exercise sciences. There is a level beyond which higher rates of metabolism require obligatory glycolytic contributions. I would almost suggest the introduction of a new term, the _____ transition (or threshold), though there are already too many terms for this phenomenon already. A more accurately descriptive term does not necessarily lend itself to any more insight to the phenomenon. In any case, I still prefer the word “transition” since I think the concept of a threshold can be misleading. For many, the term threshold connotes “a level or point at which something would happen.” While I suppose the semantics as to what a level or point mean can be debated, I prefer to think of the transition as more of a zone or gradient area as I think many fluctuating factors affect the precision of the transition (e.g., hydration, sleep, inflammation, nutrition, etc.) all of which are stochastically diurnal.

This brings us to the conversion conundrum…

The Curious Case of Chemical Conversions

One last comment is on the curiosity of macronutrient chemical conversion. As discussed, the body lacks a mechanism for storing amino acids besides their functional form as polypeptides or proteins. Carbohydrates and fats can both be stored as glycogen and triacylglycerols, respectively. When any of these nutrients are consumed in excess, the extra matter and energy can be stored as fat. Not all of it will be stored, but over time and under poor health practices, the probability of excess calories being converted into excess adipose tissue increases.

In the case of protein, the carbon skeleton of deaminated amino acids can be converted into tricarboxylic cycle (TCA, a.k.a. citric acid cycle or Krebs Cycle) intermediates that can be used either to generate ATP (via oxidative phosphorylation) or provide the precursors for fatty acid synthesis and gluconeogenesis. All but two amino acids are glucogenic amino acids and can be converted into glucose through gluconeogenesis. Thus, protein can be converted to carbohydrates and/or fat. However, humans lack the genetic material required to synthesize the enzymes found in the biosynthesis pathways for essential amino acids. We can only synthesize about half of the two-denary amino acid building blocks. We can not convert fat (or carbohydrates) into protein despite what gym-lore broscience might have you believe (or wish).

However, as humans, we do have the capacity to interconvert carbohydrates and fats. De novo lipogenesis (DNL) is a tightly controlled and intricate metabolic pathway where circulating carbohydrates are transformed into fatty acids for the synthesis of triacylglycerols or other lipid molecules. Fatty acids, specifically odd-chain fatty acids, can be converted into a TCA gluconeogenic intermediary by way of a series of biochemical reactions.

So, your body can definitely convert extra nutrients into fat to be stored. And, with the exception of synthesizing protein anew, can interconvert macronutrients. Which brings us back to our converse question…

When someone gains weight, where does the fat come from?

Many members of modern metropolises have been made aware of the calories in calories out mantra. If you continually consume too many calories, eventually, that excess matter and energy will be stored as fat in adipose tissue. So the fat comes from your diet. Duh. But where then does your diet come from?

Powered by Plants

As chemoorganoheterotrophs, our diet comes from photosynthesis. Whether vegan, vegetarian, pescatarian, omnivore, or carnivore, if you trace what you eat back through the food chain, you ultimately end up with plants.

So the carbon creating the clumps that bulk up your body’s adipocytes comes from the same stuff we are breathing every day, carbon dioxide. And, as we will see as we move into metabolism, it is the cutting up of carbon-based organic compounds that powers cellular respiration. Thus, when somebody loses weight, the fat exits the body via the lungs as carbon dioxide. In fact, a fun and informative paper by Meerman and Brown (2014) concludes that their “results show that the lungs are the primary excretory organ for weight loss.” While the water formed during fat oxidation “may be excreted in the urine, faeces, sweat, breath, tears, or other bodily fluids.” A fun fact for flabbergasting friends.

The next instalment will look at the methods of metabolism (i.e., the three stages of ATP production), anaerobic versus aerobic pathways, and the myth of lactic acid and the truth about lactate.

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Addendum

After writing this post, I came across these two Tedx Talks by one of the authors, Rueben Meerman, of the paper referenced above, “When somebody loses weight, where does the fat go?” If the question fascinated you, and you wanted a more in-depth explanation with an incredible visual of freezing your breeze so that you can see the liquid oxygen and solid carbon dioxide a person exhales, check it out!

The second video gives more of a molecular model of metabolism and is also marvelous!