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Hi Len. Hi Asami. So to start off this 科学系ポッドキャスト episode, I will start with a very profound
and important question before we get to the episode, and then maybe at the end of the episode
we can see what our answers are. And that is... Viewers, I'm reaching for a notepad. What is
your favorite ice cream flavor? Very profound. It says everything about who you are
and what kind of person you are. It determines how trustworthy you are as a friend, as a human being.
Based on this, we may reconsider our friendship. Didn't you say that about the Soba episode too?
No, after the show. No, after the show. It wasn't in the...
I'm just putting the question right there. All right. Now, so favorite ice cream flavor, right?
Okay. Favorite ice cream flavor. Yeah, think about it. Give me some thoughts.
Careful. This will affect your friendships. Okay. I've made a note. It's now in my notebook.
All right. So alongside this starter question of great philosophical nature,
what else would we like to say about the Kaguya podcast?
So for the month of October, it's hosted by Sonnai Rika no Jikan B,
and he proposed the episode to be generally about aji, which is flavor, taste.
Len shared a couple of interesting topics. He's going to talk one of them, and I'm going to talk
the other one. So do you want to start, Len? Yeah, I can start and take it from there.
So when you first mentioned flavor to me, the thought obviously was like taste buds, right?
And I was thinking about some of the materials I use in a summer course that I still sort of offer,
and this thing I'm about to talk about, actually, I also share in that summer course.
And this is a video by Steve Mould. So for anybody who doesn't know, video by Steve Mould,
does some interesting science communication videos. I recommend checking it out after I sort of...
03:03
I'm about to give away one of the sort of secrets of that video, I guess, by talking about it here.
Okay, okay. So if you want, go check out his thing first and come back, but also...
Yeah, we'll put the link in the show notes. Yeah, yeah. The question he asks is another
philosophical question, or at least it might sound like it, maybe not as friendship-dependent
or dangerous as your favorite ice cream flavor, but it is what do protons taste like?
And so, you know, so what do protons taste like? Okay. Right? Yeah, this is strange,
because we often think about taste, if we're at least maybe a chemist or a biologist,
right? We're thinking about taste and flavor as, at their smallest, compounds, molecules.
Yeah, I was thinking more like sugars, like a few atoms at least, more like a dozen of atoms.
Yeah. You know, you know, not just like one. Yeah. And tiniest one of it all as well. H plus.
Right. That's, that's normal, right? To think of flavor in terms of those instead of single
particles, right? Instead of just like a single atom of something.
Um, yeah, can we even taste them? Yeah. So I mean, people will maybe have arguments about
this. But the, the sort of walkthrough here, that Steve Mould has walk us through then
gets you to the answer of yes, there is a taste. And so like, to start us off, and I think also
prepare our listeners here for your topic that you'll bring up next. It's good to set
the baseline that we're talking about the taste receptors in our tongues at the moment.
It's actually also mentioned in this video and elsewhere, we have taste receptors and other
types of sense receptors elsewhere, which is a whole other philosophical question of whether
these are, you know, the same or related or different, but we have a lot of them on our
tongue, which we think about. And when you zoom in and in and in onto a tongue, you finally get
to these little hairs that are sitting on top of gustatory cells, which are just these cells
sitting on your taste buds, etc, in your tongue. And these cells, like all cells have a nice
phospholipid bilayer, well, all of our cells have a phospholipid bilayer. And that bilayer
has little receptor points, right points that can sense the outside world. So in our saliva,
right, that's yeah, the outside world is our saliva at that point, anything on our tongue.
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Yeah. You have sort of those lock and key type ones, you have these little proteins that
will have a little shape, there's a shape on top of them or around them, or, you know, both
physically and electrically, right, sort of shaped. And things can bind to them, such as
sugar, like you mentioned earlier. And you get a signal that says this is sweet, right? Maybe you
need this for energy, please eat this. That would be like the evolutionary reasoning behind this.
Right, which is discussed, let's say, but the lock and key is one. And then there is another one,
which is for salty and sour flavors. And these are ion channels. So these are actually like
tubes or tunnels, I like to think of them as sort of tunnels through the actual bilayer. And this
is it's like embedded in a membrane, right? Yeah, exactly. It's embedded right between there. So
instead of it being instead of it having a shape on the outside, and when a sugar, for instance,
binds to it, it changes a little bit. And then there's a response inside the cell,
you have a tunnel, which lets, in this case, charged particles travel down the tunnel
and appear on the other side. So you get a basically a difference in charge, right? You're
separating charges in this way. And you get electrical signals that get sent to your brain
for that process. So two major ways. Two major ways. We have the lock and key of a protein,
sort of something binds to a certain shape and then changes. And we have the tunnel, which is
a pathway you can go through if you are of the appropriate size and charge, for instance, to get
through that. Cool. Okay, now if we ask, what is sour? Well, sour is acidic. It's an acid.
What is acid? How do we define acid? In the simplest way, you think about it as having
H plus, right? And at least a water-based solution. Chemically speaking, it's the most
generic definition of acid is, yeah, like, does it have a free-floating H plus or something that
can become a free-floating H plus. And so of course, yeah, then you have all these molecules
and compounds, right, that release H plus to a certain extent in water or other substances, right?
It gets complicated. Right. And we're basically water, human beings. Yeah, you can think of us
as a water system. Yeah, yeah, yeah. And so if you have a bunch of H plus floating around,
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and it turns out that H plus is in fact the thing passing through the ion channel for sour taste,
acidic sour taste, and H plus is just a proton. So... I see what you did there. Yeah, well,
you see what Steve Mould did there, but that was... Exactly, exactly, that guy did. Yeah.
Yeah. Okay, okay. Yeah. So this is, it's kind of like a logic game of, you know, deducing
acid to proton and therefore proton tastes like sour, which is like, I guess it's all,
is it always true or is it only partially true? So I think it helps to think about it like,
for instance, the other ones we mentioned that are lock and key related, that are like shape
dependent, the shape, for instance, of like malic acid is important for the amount of H plus that
goes through. So the intensity of like a sourness perhaps would vary based on how much is being
released, right? Okay. I think... So whether it's detectable level of acidity or not might be
different. Yeah. I mean, if you were to like... The type of acid... If you were to lick a single
proton, which is saying a strange sentence that I would not have said. Right, right, right. You
probably need like several million ion channels with H pluses passing through to like, let your
brain recognize that you're eating something sour. You can think about it as the collection of these
things, right? It's a, if you want to use the evolutionary reasoning or not, there is a
decision, biologically speaking, that said, we need to know when this type of molecule is around,
when it is something that can generally sort of freely float protons into that space. And so
knowing that is useful. And to a certain extent it's useful. I can't just take one single... I
mean, I can't even take, I think, one sugar molecule and be like, ah, yes, sweet, right?
There's not enough... Yeah, we're probably not single molecule sensitive. No, absolutely not.
But in the essence of, well, if you dumped a bunch of protons on my tongue, which is essentially the
same thing as taking any sort of acidic compound and dissolving it, now you have a bunch of those
floating around. One of the signals you'll get is from the ion entering the channel and like
signaling your sour taste. So yeah, so short answer, right? What protons taste like? Sour.
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Is it a little quirky? Is it a little like sort of meant to make you think and then go, ah, that was
the answer, you know, at the end? Yes, that is what it's looking to have you do. And so it was
fun. It's a nice way to, I think, introduce taste and to make you sort of remember this, right?
It's shocking to think that single sort of like, even in the case of salt, right? So NaCl separates,
the sodium passes through that channel, right? The sodium has other things on it. It's not just
a proton, but like it's still just one atom, right? Like passing through and having a certain
charge. And so, yeah. It's really fascinating how something as simple as single ion or single type
of ion rather, can be responsible for so many things that happen in our brain and our bodies
in general. Yep, absolutely. And I will then now talk about my half of this stuff, where
this is also procured by land, by the way. So thanks for bringing this up in the radar.
This paper that I'm going to talk about is all about the taste of bitterness. And not in a
metaphorical bitterness, but an actual bitter flavor, like what you would feel when you drink
coffee or I don't know what other bitter things like goya. Yeah, probably. Yeah. Yeah. Something
like that. Sorry, I was thinking a question like, where does natto fall? Natto is largely umami,
I think. Okay. All right. I'm not gonna I'm not gonna lay any of my opinion on that. But I think
it's more complex than that. I think some some elements can be bitter. Who knows? I don't have
the sophisticated taste buds. Sure. It's complicated, just like bitter is. So yes,
please continue. Apologies. So we talked earlier in the episode how there are two major modes of
detecting taste, or flavor responsible molecules. One of them is through ions, as we described just
now. And the others like sweet, umami and bitter flavor. The second one where it's there's some
specific shape outside of the cell. And when those taste molecules, they they're calling
tastants, when they bind to these outside structure of the cell, it changes the structure
15:00
of the shape on the outside of the cell ever so slightly. And that cascades into signaling
inside the cell, and starts the whole process of transmitting other information and firing
electrical signals. What makes bitter taste, especially complicated, is unlike this very
simplified mechanism of sweet and umami g-protein coupled receptor pathways,
they are finding that that's not the only thing that happens. Because this class of taste receptor
that's responsible for bitter taste is not only present in on your taste buds, but it's also
appearing in your lungs, smooth muscle cells, like intestine surfaces and stuff like that,
and brain and elsewhere. So one could say that you're feeling and perceiving the bitter taste
all over your body, just crazy to think about. Wow. What they don't know at the beginning of
this study is that they know that this bitter taste are, you know, coupling with particular
taste receptors, but they don't know how biological pathways, like how biological
mechanism by which this receptor can be activated fully by cholesterols and the bile acids that's in
the body in general. So that's the unknown, that's what they set out to try and find out.
And they use, among other things, cryo-EM, cryo-electron microscopy. So this is one of the
most highest resolution microscope you can use. You can see electrons, so that's saying something.
And they found two unexpected things out of the studies. So unexpected findings. One is that
there's a cholesterol molecule in what was thought to be an orthosteric binding site,
and by orthosteric binding site, you can just think of it as like the primary site for binding.
All of these G proteins have sort of known structures, and they typically have a site
where it's like especially welcoming for the outside molecules to bind to.
But they found, instead of it being a binding site, they found some cholesterol there, instead of
the tastant molecules. So that's one. And number two, so where did they find this bitter tastant
molecules? They found it in an allosteric modulator site, which is other parts of the site,
which is primarily not the top place where you would expect the tastant compounds to be at.
So two unexpected findings. They wanted to find out why such oddity, right? Right, yeah.
18:04
And they did a bunch of molecular dynamics, other biochemical simulations and experiments,
which none of which I'm going to go through here, but they did a bunch of experiments.
But all in all, they found out that basically they need both the cholesterol and this additional
ligand to fully activate this receptor, to begin this cascading signal of electrical signals.
And they get cholesterol on the orthosteric site, they already found one, and then they're finding
that this additional ligand, where they're procuring this ligand from, is the tastant
molecule. So the tastant molecules are acting like an accessory ligand in combination with the
cholesterol to fully activate the receptor. So it's rather than this host-guest chemistry of
one-to-one reaction of one key into one host and then one signal, it's more like two
things that happen at once or sub-sequentially, I think they don't know yet.
But there needs to be two sort of conditions that needs to be satisfied before this taste
receptor can be fully activated to start this bitter taste perception cascade.
So finding that out was a big deal, because it's not as simple as something go in,
something comes out. So yeah, that was the gist of this paper, Nature paper, by the
School of Medicine in North Carolina, Chapel Hill.
Oh, nice. I hadn't actually looked at, I saw the names, but I didn't know who had done it. So,
cool. I, as you were describing this in much greater depth than I had explored this paper,
I'm starting to think like, why, I don't know enough about biology to make any type of conjecture
here, but I'm curious why cholesterol is involved at all. I imagine that's their next question,
right? Like, why is it cholesterol? I think so. They want to know why this
bitter taste receptor is participating in cholesterol metabolism pathways, because it
does seem like it's partaking in the cholesterol metabolism. And I also don't know when they say
cholesterol, what kind of cholesterol they're talking about, because it seems like based on
21:04
this paper I read, they're referring to cholesterol as cholesterol, and maybe I missed a few sentences
where they are talking or specifying about the cholesterol, but maybe it's like a general
cholesterol that exists in our bodies. That's another, yeah, that's another good question.
I'm like, I wonder as well, you've got, okay, so we assume cholesterol is just part of this
process, we see it, and we're like, okay, it must be part of the cholesterol mechanism. So
somehow in this case, at least, bitter molecules are helping to activate
the receptor, I guess, TAS2 receptors, what are they called? Type 2 taste receptors.
They call TAS2R14. Okay, awesome. Just longer acronyms.
So, okay, out of these receptors, they're, I guess, sensing, they're at least interacting
with the bitter molecules, right? And so that's somehow involved in cholesterol bouncing around
our system. I'm wondering which one is more at play. Like, is it that the bitter molecules
are just tagging along with cholesterol's overall process? Why would they need to bind to that
receptor? So many questions about this that I don't think-
Yeah, or maybe, we don't know, I think, the actual function and what kind of role it plays
in this cholesterol metabolism pathways, which is extremely complicated. But what they found out
is that the two things, which is the binding of cholesterol and the binding of the taste and
the bitter taste molecule, both needs to happen for deactivation. So my wild, wild guess is that
somehow, this is playing a key role in cholesterol metabolism, because like everything that we
produce or take in from our mouth, like, you know, things need to be metabolized and then, you know,
flushed out one way or the other. And cholesterol being fairly, you know, dense and fatty and
dense and fatty and difficult ones to metabolize, typically, like speaking chemically,
maybe requires an additional help. And that might explain why, even though,
you know, we typically associate bitter things with unpleasant sensation, like, you know,
24:10
medicine tastes bitter, or things like that. Because if you were to go with the evolutional
sort of explanations, it doesn't make sense that we want all of the bitter things,
because some bitter things are downright toxic to us. Yeah. But we learned to enjoy some
bitter things, like a very, very dark chocolate, or coffee, or I don't know what other bitter things.
Two things you said, and I'm like, yeah, people definitely like those things.
Oh, which I don't. Yeah. Well, most people do. Yeah.
So, you know, the fact that there's a little bit of gray room there, right? Because like,
you know, medicines that are good for us could also taste really bitter. Yeah. Yep. And maybe,
maybe this is our explanation. Maybe we need a certain amount of bitter things to metabolize
cholesterol efficiently. And maybe this is not the main pathways of cholesterol metabolism.
Maybe cholesterol has other, maybe ones that play sort of the dominant role in metabolizing the
different pathways that does it. But maybe this bitter molecule mediated cholesterol metabolism
is, is one some, you know, important pathways, which might explain why we haven't given up
the perception of bitterness as flavor. Yeah, I mean, we certainly don't want to get rid of it,
right? Like there. Apparently, of all these millions of evolution, we have not removed it.
Right. And it, maybe this goes to show that it's like you were saying, sort of been worked more
into the developmental process, right? Because that evolutionary reasoning is usually
poisoned. Right. And at some point there had to be an awareness that was like, not all bitter
things are poison. Some of them tend to be good. A lot of, right. A lot of people will also be
thinking about like greens, vegetables. Like there are, there are many that tend to come with
a type of bitterness, at least they're not just fruit. That's true. If we don't soften it or if
we don't mask it in some other ways by seasoning it, it will be very bitter. Right. Exactly. And
so there is, tea is bitter on its own. Yeah. Yeah. I think. Yep. A variety of teas probably are,
right? Like, I don't know. I mean, different, different teas and you can certainly mask the
bitterness by putting milk, by putting sugar in it, something. But the fact that it's bitter
27:04
doesn't change. Tannin is a bitter flavor. And yeah. You have so many people drinking alcohol.
That's not good for us. But I mean, here we are enjoying it because we like, you know,
dancing with death. I feel like that's not necessarily evolutionary.
I think that's just an awareness that like, we are able to like, change our perception of the
bitter flavor, right? We, wow, this one, it's a complex bitter flavor, you know? Yeah. Even if
this is not the most dominant pathway of cholesterol metabolism. Sure. Yeah. Dominant
doesn't mean it's not important. Sorry, not dominant. Being a minor mechanism doesn't mean
it's not important. Sometimes those minor pathways definitely critically need to happen. And we don't
know that. We're just at the beginning of finding out that these two things are coupled and they're
going to do more studies on, you know, what are the exact sequence in which this, you know, binding
site and structural changes happen. You know, me coming from a molecular dynamics background,
I'll be really curious to know sort of like the speed at which this structural change takes place,
or which one comes first. And maybe they alluded to it in a simulation, which one is like,
starts the cascade, and then it primes the other location. But,
and maybe they have, and I haven't, like, you know, I kind of skimmed through and forgot to
see carefully. But, you know, they're kind of like, is it sequential? Or is it kind of all at once?
You know, is it kind of like a simultaneous process? But so that was it. And I thought
that was interesting. I'm usually not the one to read biochemistry papers. So thank you for
sharing this. It was interesting. It's fun to read sometimes things outside of your immediate
interest. You know, that sometimes things that you take it for granted, like I can taste the
bitter flavor. What more do I need to know? You know, like sometimes things like that,
we still, turns out we still don't know why. Yeah. Yep. It's a, that's pretty exciting. A bit of a
surprising reveal, which can, yeah, exactly. It can be really exciting. We can share, maybe link
wise, we can share the link to that article, the link to maybe the chemical engineering news one,
just because it's easier for some people to probably read. Yeah, yeah. Easy highlights.
And then we'll share the video as well. So yes, so like to close off this episode,
if you listen this far into it, you deserve to know the answer. Then what is your favorite
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ice cream flavor? Why? Why do I have to start first after you set this up with? I mean, I can
start like, if it's if it has anything to do with chocolate, I swear, I'll just close this zoom call
right now. I have no judgment against people who hate chocolate. I only just think that you're
missing out on an easy joy of life. But, you know, easy to live for slightly, I don't know,
miserable life. favorite, favorite ice cream flavor, right?
You can specify like, this flavor in general, or this flavor from this shop or this brand?
Yeah, I was gonna say there's, there's one that I probably wouldn't eat a lot now. But I would
say is the one that I personally enjoyed the most. And it was specifically from
Did you ever go to a friendlies?
No, no, I think they were sort of, I don't know if they were going out of business or sort of
like, you know, disappearing. They were essentially like the family restaurants. Like, okay, right,
like a size area or a pick another one, Jonathan, right? They had that sort of vibe. They
didn't do like the sort of drink bars and stuff that that wasn't totally a US thing. But what
they had was something similar to a blizzard from, you know, Dairy Queen, DQ is also a popular one.
Um, is this like a slurry type drink?
Yes, except I feel like using the word slurry sounds so gross. In terms of like,
I mean, it's pretty gross.
Okay, the the ones from DQ,
you're talking about this like a frappuccino type.
I think that's what I think it's what the Dairy Queen is. I never really had the Dairy Queen one,
but people would like try to compare it to that.
Like the ones in 7-Eleven?
No, no, those are slushies. Not slurries. What are
like the slushies? Yeah, the ones the ones that are okay, no, no problem. That's okay.
Yes, slurry sounds like like, like a clathrate slurry.
Yeah, it's when you said it, I was like, I feel like you have a lot of disdain for this specific
drink. I mean, they're not that far from each other.
Okay, all right. Well, you do have disdain for that drink. But the No, that's not what I'm
talking about. Um, it was, this one is the childhood one. And that'll give you the one
that I kind of usually go for maybe now. Okay, this one was a base of vanilla ice cream.
But it had, it had frosting whipped into it. So like, like sugar frosting, right? Like frosting,
33:04
with little pieces of cake inside of the ice cream. And I think sometimes they'd add some
sprinkles on top or something. It was a very, it was like a very, you know, birthday cakey,
I think it was called like the birthday cake friends frenzy or something, right?
Um, and it was, you know, it was a sugar high on sugar high.
It was like, sounds like a great American invention. Yeah, it was I was like, this thing
is the bomb. This is so good. And you know, because I was like, I was like, sugar is the
best thing ever, right? When you're in high school or younger, you had access to when you're like,
Hey, yeah, yeah. Oh, no, it made it till high school that I was eating this thing. But
like, um, so I think what that left me with is that what I'll usually do when I go to
ice cream places now, and I like I did this in while we were in grad school, is that I'll try
their cake batter ice creams. And so like, because they're always different. Like,
most of the time, they're doing something different. Either they've tried to like flavor
it and kind of blend it into a single ice cream. Or they've tried to add bits of like cake and
things throughout the ice cream and like, like sort of change it up texture wise. So you get
a range of things when you try this flavor. And so I had often tried that one, right? That's like,
I'll test and see what they've done.
Cake ice cream hybrid of some kind. Yeah, it's like a go to for it. I have like safe flavor
ones that I'll do as well. But that's that's like, if I see it, I'm probably gonna I'm probably gonna
try it because I could be really excited if it turns out to be good. So yeah, yeah. All right.
Well, that's your answer.
I Oh my god, that could not have been more.
Wow, that's
I just wanted to start off the episode with a pseudo profound statement by asking this very
philosophical question. All right. That is that is my answer then? Yes. So and we can we can we
can psychoanalyze off mic. What that tells us we can we can let the listeners psychoanalyze if they
want. No, they can. Yeah. So are you gonna you're gonna give us yours? Or is it just me that's
sharing my ice cream flavor? Let's let's psychoanalyze this in the next episode. And I'll
show you what I do with like, and then I'll share in there. What is my go to flavor listeners? I
think I've fallen for a trap. Maybe. That's it for the show today. Thanks for listening and find
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us on x at Ego de Science. That is E I G O T E S C I E N C. See you next time.
