Quantum Biology [Part 2] – Enzymes, the Engines of Life

This is Hell Creek, Montana. 68 million years ago, a small T rex died somewhere
around here, and over time, minerals replaced its bones which turned its body into a T rex
fossil. In the year 2000, scientists dug it out of
the ground, and shipped some of it to a museum, and some of it to a paleontologist named Mary
Schweitzer. When she first saw those bone samples, she
noticed that they looked a little different than normal bone.

So she put the sample in an acidic solution
hoping to reveal some of the deeper bony structures. After a few days, the sample had completely
demineralized. But it left something interesting, a bendable,
fibrous substance that looked like blood vessels and a tough connective tissue called collagen
— some of the kinds of soft tissues you’d see in normal bones.. /That/ was not supposed to be possible. Up until this point, we’d only seen /evidence/
of soft tissue, not intact soft tissue.

It was thought that this kind of tissue would
get disintegrated really quickly after the organism died, but here they were millions
of years later. Naturally, the paleontology community was
a little skeptical, so to prove her point. Shweitzer dipped her vintage collagen in a
very specific enzyme called collagenase, and the collagen that stayed strong for 68 million
years dissolved in half an hour. And some scientists think enzymes like collagenase
might work because of quantum physics. But how do they know that? First some background. Left by itself, collagen will break down eventually. But adding an enzyme makes that breakdown
process happen over a trillion times faster. And that’s enzymes’ whole thing. They speed up chemical processes by a lot. Look at one process that we do all the time:
our cells consume oxygen and produce carbon dioxide as a byproduct,
A little bit of that CO2 dissolves in the blood, some attaches to the hemoglobin in
our red blood cells, but most of it gets converted into carbonic acid so it can be transported
to the lungs and breathed out.

Again, that conversion can happen unassisted,
but we have a lot of these CO2 molecules to get rid of, so we need to find a way to do
a lot of it and do it fast. Without a catalyst, this reaction happens
about once every ten seconds. But add an enzyme called carbonic anhydrase,
and now it happens a hundred thousand times every second, that’s about a million times
faster than without the enzyme.

Enzymes are so useful because they can speed
up chemical reactions, from the ones we use in our day to day physiology to the ones we
try to manipulate through pharmaceuticals. ACE inhibitors like benazepril or lisinopril
are common blood pressure medications. ACE stands for angiotensin converting enzyme,
angio for vessel, tensin for tension, or pressure. So when angiotensin is converted via this
enzyme, it tightens up blood vessels. By inhibiting this enzyme, you’re encouraging
the blood vessels to dilate and lower blood pressure and that’s what these drugs do.

There ya go. They’re not just useful for dinosaur tissues. Enzymes are everywhere! And you can usually spot enzymes because they
end in -ase. Lipase, helicase, maltase. All are enzymes and end in -ase. And those prefixes usually tells you what
they do. Lipase breaks down lipids. Helicase unravels the DNA helix. And Maltase breaks maltose into glucose. No matter what enzyme in the human body you’re
looking at, they all make biological processes happen faster. And for decades, classical mechanics has offered
a totally reasonable explanation for how they work. Big picture here — some of our physiology
requires energy to go from reactants to products. We often use this graph with energy on the
y axis and the completion of the reaction on the x axis. Without the energy to get over this hill,
the reaction won’t happen. In 1948, an American scientist named Linus
Pauling had the idea that enzymes can lower the energy hill because of how they fit together
in something called transition state binding.

See, each enzyme is specially built to bind
to one particular reactant, or substrate, kind of like puzzle pieces. But enzymes aren’t a perfect fit until the
enzyme and the substrate tweak their shape a little bit to fit really tightly together. When they do, the enzyme-substrate combo is
said to be in transition state which lets it break the chemical bonds of that substrate,
ultimately speeding up the reaction.

Afterwards, the substrate turns into the products
and the enzyme can go on to catalyze more reactions. This general concept still holds to modern
day — enzymes lower the activation energy so the reaction happens faster. No quantum chemistry needed, classic chemistry
still applies. Fast forward to 1966, researchers at the University
of Pennsylvania saw a reaction that defied classical models, so they explained it with
quantum physics. They observed a photosynthetic bacteria that
uses light to oxidize a protein called cytochrome. When it’s exposed to light, it photosynthesizes
— the cytochrome donates an electron to the molecules around it.

This reaction was shown to be temperature
dependent. Hotter conditions increased reaction speeds,
colder temperatures slowed them down. Adding an enzyme into the mix still increased
reaction speed, but ultimately the whole thing could be influenced by temperature. Here’s where things get interesting, that
reaction had been demonstrated even at extremely low temperatures. Like way below zero Celsius. To figure out how this worked, they came up
with a machine that would let them shine a super fast, high energy laser at these bacteria
and trigger their enzymes to make the reaction happen. They fired their laser at the bacteria and
measured the reaction speed.

They found that as they dropped the temperature,
the reaction speed dropped…until they hit -173oc at which point the reaction speed hit
a plateau and didn’t drop with temperature anymore. This plateau happened all the way down to
-238oc. So the reaction still had to climb over some
kind of hill but according to classical mechanics, the enzyme shouldn’t be able to lower the
hill as much as they saw in those extremely cold temperatures. In their paper, they proposed that enzymes
weren’t helping the reaction to “lower” the hill, maybe they were burrowing through
it. This was the first experimental evidence that
maybe quantum tunneling could explain this temperature dependent biological phenomenon. Now I’m not even going to pretend to be
an expert on quantum tunneling, so I’m going to hand it over to Jade from the youtube channel
Up and Atom to let her explain it. Take an every day classical scenario, like,
trying to roll an object over a hill.

If the object isn’t given enough energy
to get over the hill, it’ll simply roll back down. It doesn’t matter how many times you try,
or for how long, if it doesn’t have enough energy, it will never get over that hill. Things are different in quantum land. If a particle doesn’t have enough energy
to jump a barrier, sometimes it can still make it through to the other side. This is because of a phenomenon called wave-particle
duality. See in the quantum realm, particles sometimes
act sometimes like particles, but sometimes like waves. This wave represents the probability of them
being in a particular place. So instead of a particle traveling toward
a barrier, imagine a wave of probability.

Now when this wave hits the barrier, unlike
what a particle would do which is get 100% rebounded, a tiny tiny fraction of the wave
seeps through. Now because this wave represents the probability
of an electron being there, there is a tiny tiny probability that the electron will end
up being there. So sometimes, even when a quantum particle
doesn’t have enough energy to jump a barrier, because of its dual wave like nature, we can
find it on the other side. The results of that experiment in the 60s
offered an explanation for how electrons act more like waves than particles, at least at
extremely low temperatures. Now, electrons are really tiny which makes
them more likely to tunnel than bigger particles like protons or neutrons. But about a third of the enzymes out there
work by facilitating the transfer of Hydrogen atoms, which are mostly proton. So the next challenge for quantum biologists
was to figure out if Hydrogen can tunnel too.

In 1989, a team of researchers led by Judith
Klinman out of Berkeley set out to prove that this happens thanks to something called the
kinetic isotope effect. Atoms get their identity based on how many
protons they have. Hydrogen has one proton, carbon has six, neon
has ten. But atoms can have different numbers of neutrons
in their nucleus, which we call isotopes of that atom. Hydrogen atoms usually have one neutron, but
can come in isotopes where they have two or three neutrons. The interesting chemical properties of an
element usually come from its electrons. Changing its neutrons won’t change its reactivity
much, but it will change how heavy it is and how quickly it reacts, hence kinetic in kinetic
isotope effect. Assuming all other conditions stay the same,
substituting a heavier isotope of hydrogen ought to result in a slower reaction rate.. Classical mechanics can predict how much faster
a light isotope will react than a heavier isotope and give it a numerical value.

I’m not gonna confuse you with the calculations
itself, but just know that it’s something that can be predicted. Klinman was interested in an enzyme called
alcohol dehydrogenase, or ADH, which catalyzes this reaction, a hydrogen atom is transferred
from benzyl alcohol to benzaldehyde. Replacing the lightest isotope,with the heavier
isotopes should slow down the reaction. But from a quantum perspective, as soon as
you add another neutron onto that hydrogen atom, the ability for it to tunnel drops significantly. For Klinman, the heavier hydrogen isotopes
should react much more slowly than predicted. Sure enough, that’s exactly what her group
observed. Protium was catalyzed so much faster than
its heavier isotopes that, according to this research group, it had to be acting more like
a wave than a particle and thus, it had to be tunneling. Now, this experiment was conducted at 25oc,
about room temperature, which is kind of the kicker here. Life happens at warm temperatures from a quantum
perspective.

The warmer the temperature, the less likely
quantum mechanics has any effects. It’s something called quantum decoherence. So in follow up experiments published in 2004,
Klinman and colleagues used the same enzyme and reaction and found that above 30oc, the
reaction behaved as predicted by classical mechanics. No quantum mechanics needed. So At the sub zero temperatures where enzyme
quantum tunneling is appreciable, it’s too cold for life to thrive, so is any of this
relevant.? Well, sure, it’s relevant. But instead of simply bestowing my blessing
on the quantum biology model of enzymes, I want to draw a more nuanced conclusion.

If we revisit Mary Schweitzer and the T rex
collagen, we see an enzyme at work. Collagenase catalyzed the separation of chemical
bonds that had held strong for tens of millions of years. For the temperature and enzymes involved quantum
decoherence probably prevented any involvement from tunneling, so our dinosaur model probably
doesn’t use quantum tunneling.. For the temperature and enzyme involved, quantum
decoherence probably prevented any involvement from tunneling, so our dinosaur example probably
doesn’t involve quantum physics. To give this model some credit, there are
a lot of unanswered questions within the study of enzymes. And maybe these initial experiments are the
thin end of the wedge and quantum biology might help us answer them someday. The books and papers that I read to research
this video are obviously going to say that quantum biology is the coolest thing ever,
but hopefully this video shows that it’s more complicated than that.

There is some evidence that some enzymes use
quantum tunneling in some situations. But that’s all we can say. For now. If you’re sitting there thinking “dang,
this is dope, I want to learn more about this” then go check out the video Jade and I made
on her channel and while you’re there, make sure to subscribe to her, she’s really good
at making difficult topics understandable. And thank you to my Patrons on Patreon. I couldn’t do it without ya. To everyone else, like the video, subscribe
if you haven’t and hit the bell so you get notified when I post new videos. Have fun, be good. See you next time!.

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