Enzymes are the toolmakers of life: protein molecules that accelerate chemical reactions by factors of millions to trillions, often at mild body temperature and in water. How they do it is explained classically in the textbook – they lower the energy barrier that a reactant must "climb" over. But in transferring the lightest building block of all, hydrogen, a second, deeply quantum-mechanical option comes into play: the particle does not go over the barrier at all – it goes through it. It tunnels. This is the most broadly accepted example of quantum biology – and here too it is worth looking closely at what is established and what remains contested.
What "tunnelling" means
In classical physics, to roll over a hill a ball needs at least the energy corresponding to the hill's height. If it lacks that, it stays put. In quantum mechanics, however, a particle is at the same time a wave: its probability of being somewhere reaches a little way into the barrier – and, for a thin barrier, even through it. With a certain probability the particle appears on the other side without ever having had the energy to reach the top.
How strong this effect is depends sensitively on mass: the lighter the particle, the more pronounced the tunnelling. Electrons tunnel effortlessly (the first step of photosynthesis and of the respiratory chain relies on it). The hydrogen nucleus – a single proton – is about 1,800 times heavier than an electron, yet still the lightest of all atoms. Just light enough for its tunnelling to become measurable in biochemistry.
The detective: kinetic isotope effects
How do you detect something so invisible? With an elegant trick. Hydrogen has two heavier siblings: deuterium (D, twice the mass) and tritium (T, three times) – chemically almost identical, only heavier. Replace the migrating H in the substrate with D, and the reaction runs more slowly. This ratio of rates is called the kinetic isotope effect (KIE).
The decisive point: purely classically (that is, if the H went "over" the barrier), the KIE at room temperature is at most around 7. Tunnelling, by contrast, depends exponentially on mass – and so produces two tell-tale signatures: unusually large KIE values far beyond this classical ceiling, and a striking temperature dependence. Find these fingerprints and you have caught tunnelling in the act.
Three key findings
Yeast alcohol dehydrogenase (Cha, Murray & Klinman 1989). Judith Klinman and colleagues provided in Science the first clear evidence of significant hydrogen tunnelling at room temperature in an enzyme. By comparing H/T and D/T effects they showed deviations that cannot be explained classically – the hydrogen particle took the shortcut through the barrier.
Soybean lipoxygenase-1 (Knapp, Rickert & Klinman 2002). This enzyme is the showcase. It transfers a hydrogen atom with a KIE of about 81 near room temperature – eleven times the classical ceiling – and does so with a surprisingly weak temperature dependence. The two together are the textbook signal for a reaction that proceeds essentially entirely by tunnelling. There is hardly a clearer example of a quantum effect right in the middle of metabolism.
Aromatic amine dehydrogenase (Masgrau et al. 2006). Here a group around Nigel Scrutton combined crystal structures with simulations and delivered in Science an atom-level picture of a reaction "dominated by proton tunnelling" – the transfer happens over a tiny distance of about 0.6 ångström. Tunnelling was thus not merely inferred from rates but traced down to the level of individual atoms.
The real dispute: does the protein actively help?
That hydrogen tunnels in many enzymes is now broad consensus. What is fiercely debated is something else – and here care is needed. Researchers such as Klinman and Scrutton hold that the protein is not mere scenery: certain fast vibrations of the protein scaffold ("promoting vibrations" or "gating") press donor and acceptor atoms close together for a fraction of a second and so narrow the barrier – the protein dynamics would thus deliberately favour the tunnelling. On this reading, the enzyme's precise internal motion is part of its catalytic power (Klinman & Kohen 2013).
Others, around Arieh Warshel for instance, push back: tunnelling is real, but does not explain the lion's share of the enormous acceleration. That comes mostly from classical electrostatic preorganisation – the enzyme arranges its charged groups to stabilise the transition state. An independent, catalytically "useful" dynamics that drives the tunnelling is, they argue, unproven. The debate is therefore not about whether tunnelling occurs, but about its weight and whether the protein's motion steers it.
What is established – and what is not
Let us separate cleanly. Established is: hydrogen tunnelling occurs in numerous enzymes, well evidenced by large, anomalously temperature-dependent isotope effects and, in individual cases, modelled atom by atom. It is not a laboratory stunt at minus 200 degrees but runs at body temperature, in the thick of metabolism.
Open is: how much tunnelling contributes quantitatively to the fabulous acceleration, and whether the protein actively promotes it through targeted vibrations. Here serious camps face off, and the matter is not settled. Anyone who writes "enzymes owe their power to quantum tunnelling" overstates; anyone who writes "tunnelling plays no role" does too. The truth is in between – a real quantum effect whose precise role is still being measured.
The third part of a trilogy
With this a triad closes. For the magnetic compass of migratory birds the quantum explanation has strengthened over the years; for photosynthesis it has weakened; for enzyme tunnelling it is broadly accepted, and the argument is only about degree. Three stories, one pattern: the quantum world is no exotic add-on to life but is woven into its basic chemistry – and honest science here follows the evidence, not the lure of the catchy thesis.
That same discipline is also the measure when the field reaches its speculative edges – the question, say, whether quantum processes play a role in the brain, as Penrose and Hameroff's Orch-OR model assumes. That a proton tunnels through an enzyme barrier is well established; that consciousness follows from it is not. The real quantum effect in metabolism makes the larger question more interesting – but does not answer it.
Sources:
• Cha Y., Murray C. J. & Klinman J. P. (1989), Hydrogen Tunneling in Enzyme Reactions, Science 243(4896):1325–1330 (doi).
• Knapp M. J., Rickert K. & Klinman J. P. (2002), Temperature-Dependent Isotope Effects in Soybean Lipoxygenase-1: Correlating Hydrogen Tunneling with Protein Dynamics, J. Am. Chem. Soc. 124(15):3865–3874 (doi).
• Masgrau L. et al. (2006), Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling, Science 312(5771):237–241 (doi).
• Klinman J. P. & Kohen A. (2013), Hydrogen Tunneling Links Protein Dynamics to Enzyme Catalysis, Annual Review of Biochemistry 82:471–496 (doi).
Continue in our curated knowledge collection – see also the articles on the quantum compass of migratory birds, on the quantum biology of photosynthesis, on quantum entanglement and on the fundamental question of brain and consciousness.