A hallmark of living organisms is that they depend on gradients in order to develop properly, to organize themselves, to identify predators and - most importantly - to fuel the cellular processes that make all of these things possible. Finding ways to turn food into fuel is the central task of all living beings - and it turns out that most of them agree on the most efficient way of doing so. From single celled bacteria to the most complicated multi-celluar beast, cells use fundamentally similar mechanisms to transfer motion from the food they eat to the work they need to do. Cells have evolved ways to let things fall apart in such a way that the disorder can be harnessed for orderly work - movement, growth, and reproduction.

What is food?

In the simplest possible way, food is a substance that an organism consumes to power anabolic processes - those that build things. For humans, the realm of “what is food” is pretty constrained. It takes only to look back through history to realize that famine has almost always been around the corner, mostly because we can’t eat too many different things. The food and water we consume has to be free of contaminants that make us sick, and our slate of nutrients is limited to fat, protein, and carbohydrates. Plants, those peaceful sun-harvesters, get most of their nutrients out of the soils in which they grow, usually through collaboration with fungi and bacteria. Bacteria, on the other hand, present an astounding collection of metabolic flexibility. They can eat everything from plastic, to metal, to rocks, to radioactive waste. In the next weeks we’ll spend some time figuring out the metabolic complexity of those other systems, but before we get there, I’d like to take a look at the human biology of how we come to be what we eat.

Back to Basics

In high school biology, we were taught that ATP, adenosine triphosphate, is a highly energetic molecule that is used by cells to pay for costly activities. It was said that the energy was stored in the bonds of the molecule, that there was something special about releasing that third phosphate from it’s tenuous position on the end of the chain - but the reality is a little bit more interesting. The fuel that ATP provides for all of these activities does not actually come from the molecule itself - it comes from the food that you eat, and ATP is simply a convenient way to carry it through the body. Let me try to illustrate it:

Section A of the figure above is nutrient intake - eat a big meal, or even a little one - and you’ll take in nutrients, probably with some vitamins, maybe even some minerals. The main three - fat, protein, and carbohydrates are what’s called macronutrients. The vitamins and minerals, micronutrients.

Once you ingest food, the physical and chemical processes of digestion begin. Chewing tears the food into smaller chunks, amylases in the mouth start to break down carbohydrates, acids in the stomach break up the proteins. The churning of the walls of the stomach produces a homogenous mixture, chyme, that’s released into the small intestines. In the small intestines, liver enzymes come onto the scene to help process the fat, and the peristaltic motion of the intestines themselves mixes and moves the food through the body.

The mixture of broken down food and enzymes flows over the walls of the small intestines, where the massive surface area allows for maximal reabsorption of nutrients into the blood. These nutrients are in their elemental form at this point - they circulate in their more simplified forms so that they can easily be absorbed by the cells that need them for continued function as quickly as possible.

Microvili of the small intestines. They increase surface area to ensure maximal nutrient absorption.

Section B represents the fate of these nutrients once they get inside the cell. Macronutrient inputs are broken down into smaller parts, some of which become part of the reservoir of raw material that can be used to build new cells. The rest of the nutrient input, however, is processed rigorously and then shunted into the main show - the cyclic process that are happening inside of the mitochondrion.

Section C represents the fate of macronutrients once they’ve been processed in the cytosol, and brought into the lumen, the internal cavity of the mitochondrion.

Sliced open mitochondria, showing the convoluted inner membrane. The darker green space is the lumen, where the cyclic reactions of metabolism occur

Inside the lumen of the mitochondrion, there’s a collection of enzymes that repeat the same set of motions, over and over again, for the entire lifetime of the cell. The mitochondrion has only one job, to transform the diverse nutrients that we consume into a single molecule that can be used by all organisms to power the reactions of life.

Each turn of the cycle starts and ends in the same place. An enzyme takes macronutrient freshly imported into the lumen, and attaches it to a molecule of oxaloacetate. This creates a third compound, citric acid, for which the whole process is named.

Citric acid is then passed from enzyme to enzyme, and each handoff changes it’s shape and organization slightly. By the end of the cycle, the final enzyme is holding a molecule of oxaloacetate. It then attaches another molecule of the macronutrient, and the cycle begins again.

The intermediate steps of this cycle, the ones between citric acid and it’s return to oxaloacetate, is where the really astounding thing happens.

Every step in this cycle happens spontaneously.

This cycle is a quiet vortex in an otherwise unstoppable orgy of consumption. The shuffle of carbon and hydrogen that happens during these nine steps is a spontaneous process that cells use to produce the molecule, ATP, that powers everything else.

In the figure above in section C, there’s two more cycles next to the carbon cycle. The first of these is the NAD/FAD cycle, and it is the mechanism by which hydrogens can be moved around the cell with purpose. During the carbon cycle shuffle, when hydrogens are pinched off of the carbon compounds at the center of metabolism, they’re handed either to NAD or FAD. Both of these compounds reversibly accepts a hydrogen atom. Once they take a hydrogen away from the carbon cycle, they transfer it to the second half of the main attraction - the inner membrane of the mitochondrion.hydrogen away from the carbon cycle, and brings it over to the main attraction: the inner membrane of the mitochondrion.

The inner membrane contains the last few pieces of cellular machinery necessary to harvest the electrical potential stored in a glucose molecule. There’s an enzyme complex there, complex 1, that’s perfectly happy to take the hydrogen away from NADH. The hydrogen is then moved into the intermembrane space of the mitochondrion, the movement of which is coupled to the splitting of a diatomic molecule of oxygen into two molecules of water. The reservoir of hydrogen ions in the intermembrane space is then allowed to flow through the very last piece of the entire process - ATP synthase. It’s a huge enzyme complex with many moving parts that, with each hydrogen ion that passes through it, is able to take an a molecule of inorganic phosphate and screw it onto the end of a molecule of adenosine di-phosphate.

The many subunit ATP synthase. Hydrogens fall through the center of the complex, which turns like a turbine. With each ratcheted turn, one ATP is regenerated from an ADP.

The ATP that’s produced by this process is then shuttled into the cytoplasm, where it’s used for the processes marked in Section D - the anabolic processes of growth and reproduction, as well as the expensive process of movement.

What’s important to remember is that ATP is not consumed, per-se. It’s simply discharged, and the cell has an excellent mechanism for recharging it as long as macronutrients and oxygen are available.

TL;DR

Humans are constantly preoccupied with the question of how to power our lives. Electricity, which we all depend on, is mostly produced through consumptive processes. The vast majority of our fuel comes from burning things. Studying the various ways that cells harvest power from what’s available in the environment can inform how we design and implement our own power grids.

Human metabolism requires enormous power harvesting in order to provide the motive force for all of the costly processes that are constantly happening inside of our cells - from growth and division down to the costly transfer of compounds and out of cells.

Animal metabolism has addressed this by coupling a set of spontaneous reactions to the breakdown of a narrow selection of nutrients. What we lose in metabolic flexibility we gain in efficiency. The only piece in the process that is entirely consumed is the initial macronutrient molecule, and a single molecule of diatomic oxygen. All other pieces are cyclic and infinitely recyclable.

Life occurs where there are gradients, and cells are magnificent creators of their own gradients, able to create them through complex biofeedback networks that slow down or speed up enzymatic processing in response to changing conditions in the cell. The cyclic nature of it all is exemplified by the astounding statistic that an average person, over the course of the day - consumes something like 50kg of ATP. Since our bodies aren’t mostly ATP, cells get around this by using the process outlined above, that allows them to recycle ADP into ATP at an astounding rate.

This process is fundamental in all organisms that we know of. There literally are no organisms that have ever been discovered that do not use ATP as the mechanism for doing work. The question I have, is how can we use what we know about biology to inform our own processes of harvesting electricity?