[Like New Horizons waking up for its arrival with Pluto, this blog is blinking back to life after a long hiatus.]
Our bodies are not in equilibrium with their surroundings, but energy and matter flux through them in a steady state, maintaining the structures and reactions that give us our form and movement. The human body keeps up a carefully controlled internal environment, watery and full of many dissolved compounds such as phosphate, chloride, and ions. It’s amazing how fundamental and far-reaching this idea of maintaining an internal environment (called homeostasis) is—it’s essential to life as we know it today and raises deep questions about the origins of life.
Some ions, like sodium, potassium, and many metals, come from ingesting common salts. Another type of ion in our body fluids is H+, the nucleus of hydrogen, also known as a proton. It’s an intrinsic component of watery environments and the chemical reactions that take place in those environments; its concentration is denoted by pH, a number scale where lower values signify higher H+ concentration, which means greater acidity.
pH is controlled very sensitively throughout the body because the right acid-base balance is essential for the structures, stabilities, and interactions of proteins, which comprise many structures of our bodies and control chemical reactions. From the scale of whole organ systems down to the scale of subcellular compartments, pH is regulated by robust and sophisticated mechanisms. Incidentally, appreciating this goes a long way toward explaining why the “alkaline diet” and other diets or products claiming to fix acid-base imbalances in our bodies are pseudoscience and wrong.
What are some of these mechanisms? As H+ levels in cells and in fluids outside of cells, including blood and interstitial fluid (tissue fluid), increase as a normal byproduct of metabolism, molecules such as carbonate can buffer, or “soak up”, the extra H+. Carbonate supply in the blood can be adjusted by changing breathing rate, metabolic rates, and by the filtering of carbonic acid (the product of carbonate soaking up H+) in the kidneys. The kidneys adjust H+ levels during other filtering steps, too, which are coupled with pumping sodium and other ions and compounds. In addition to the work done by kidneys, blood, and cell fluids, the body’s fluid volumes, ion concentrations, osmotic pressures, and pH are also being tightly controlled by the liver, endocrine system, and gut. The body keeps all these intertwined rates and processes calibrated constantly and automatically.
The turnover of H+ through normal metabolism is actually a huge quantity that dwarfs what could supposedly (in the pseudoscience claims) come in through diet. Those claims already seem to neglect that the stomach contents are extremely acidic (to facilitate digestion of proteins) and then get balanced by base in the small intestine. The point is that body pH is controlled internally and without interference from your diet. Your arterial blood will stay steady at pH 7.4; venous blood at 7.35.
According to biochemists’ and cell biologists’ best measurements to date, the pH of the bulk fluid in cells is about 6.85 (this, not pH 7, is neutral pH at body temperature). Not just kidney cells but all cells have ion transporter proteins to control the flow of H+. It’s vital for the integrity and function of proteins, for regulating the cell life cycle, and for establishing a chemical environment conducive to metabolism. In particular, the mitochondria, which are the cell’s subcompartments in which most metabolic reactions take place, have a double-membrane structure: very high pH (alkalinity) is maintained in the core of the mitochondria and low pH (acidity) is maintained between the membranes. This difference in H+ concentration is a form of energy and is the essence of metabolism: food energy is used to pump H+ into the intermembrane space, and then the gated flow of H+ back in powers the creation of ATP, which is the cell’s energy currency for many other reactions.
If this is so essential to life as we know it, did early cells also depend on pH control? Did they convert and store energy by coupling chemical reactions with proton pumping? There are good reasons to think they did.
This mechanism of energy transduction, called the chemiosmotic theory, seems to be the best solution to the problem of how to get the energy of certain chemical reactions (eg breaking down sugar) to drive other reactions (eg building proteins). It would actually be very difficult to meet the thermodynamic requirements of all sorts of biological reactions if all you had were a “primordial soup” and energy input from light; compartmentalization and ion (especially H+) flow are needed to get the thermodynamics right. The chemiosmotic solution to this problem is ubiquitous across the domains of life: all organisms on earth use an ATP synthase protein for energy transduction, meaning that they share a common ancestor that performed energy transduction with largely the same proteins and compounds we use today, with an overall architecture like that of the mitochondria described above—alkaline inside, acidic outside.
Oceanographers and geochemists discovered a geochemical analog to this architecture about a decade ago in the Lost City hydrothermal vent system at the Mid-Atlantic Ridge. Strongly alkaline and warm fluid, generated by reactions in the rock below, circulates through intricate pores in 60-meter towers made of calcium carbonate. The alkaline fluids, rich in hydrogen (H2 not H+) and methane, are separated from acidic ocean water by thin inorganic membranes around the pores, a natural setting for the chemiosmotic architecture required for life. The ATP synthase protein could have originated and evolved to take advantage of this geochemistry, with lipid membranes arising soon after to augment the inorganic membranes—it has been shown that hydrocarbons similar to those in our cells’ lipid membranes are formed by the hydrothermal vent chemistry.
It would be poetic to learn that our biology is the legacy of such a place—that our cells mirror the geology and chemistry at the bottom of Earth’s oceans. We would be “of this earth”.
Cockerill, G., and Reed, S. (2011). Essential Fluid, Electrolyte and pH Homeostasis (Hoboken: Wiley).
Lane, N., Allen, J.F., and Martin, W. (2010). How did LUCA make a living? Chemiosmosis in the origin of life. Bioessays 32, 271–280.
Madshus, I.H. (1988). Regulation of intracellular pH in eukaryotic cells. Biochem J 250, 1–8.