Copperheads 4: Copper metabolism and Wilson’s disease [CC]

Copperheads 4: Copper metabolism and Wilson’s disease [CC]

Hello Copperheads! My name is Cupri and I’m so glad you’re
back! Today is Wednesday, February 28th, and also
Rare Disease Day 2018! On Monday two days ago I released an Augmented
Reality effect for Facebook camera, which you can use if you or someone you love has
Wilson’s disease. I made a post about how to find it and use
it, so if you’re interested go check out the Facebook page. Anyways, let’s get started. Last week we learned that pathogenic mutations
in gene ATP7B cause this gene to not make protein ATP7B in the right way. You can watch that video by clicking up here. And today, today, today we are gonna learn
about about how problems with protein ATP7B, also called copper-transporting ATPase 2,
affect your copper metabolism and cause Wilson’s disease. In order to do this, first I need to tell
you about healthy copper metabolism, in other words, what happens if you don’t have Wilson’s
disease or any other condition affecting how copper is processed in your body. But in order to do that, I need to tell you
a little bit about chemistry. Now, even if you don’t like chemistry, please
bear with me, I will keep it really simple, and this is only gonna take 3 minutes, I promise. Let’s do this! Your body, your house, the street, the Earth,
the stars you see on the sky… all the physical objects you see and interact with every day
are made of different kinds of atoms. Atoms are so small we cannot see them with
the naked eye or even with normal light microscopes. The different kinds of atoms are called the
chemical elements. This is the periodic table. It shows all the chemical elements that exist
and have been observed by humans. If the last time you studied chemistry was
years ago, this periodic table probably looks a little bit different from what you remember,
because we are still discovering new chemical elements nowadays. Each language has its own names for the chemical
elements, and in order for everyone to understand each other, in science we refer to them with
symbols that are either 1 or 2 letters long. And right here is copper. This Cu in the middle is the symbol for copper,
and this 29 is the atomic number. But why 29? Well, here is a diagram of a copper atom. In the middle we have the nucleus, which is
made of protons and neutrons. Protons are particles with positive charge,
and copper has 29 of those; that’s why it has an atomic number of 29. If it had 30 protons, it wouldn’t be an
atom of copper anymore, it would be an atom of zinc. On the other hand, neutrons are particles
with a neutral charge; the number of neutrons can change a little bit, and copper is still
copper. So that’s it for the nucleus. Then, going around the nucleus, we have the
electrons, which are particles with a negative charge. If a copper atom is in a neutral state, it
has 29 electrons, which balance out the 29 protons in the nucleus. But atoms can exchange electrons with other
atoms and groups of atoms around them. For example, if an atom of copper gains one
electron, it becomes a Cu− ion, and it has more negative than positive charge; similarly,
if an atom of copper loses two electrons, it becomes Cu++, and it has more positive
than negative charge; and so on. Copper is everywhere; inside many cables,
in the soil, in your food, in your body, etc. When talking about human nutrition, we say
that copper is a mineral essential micronutrient. Mineral in this context means that it’s
a simple chemical element; not all chemical elements are minerals nutrients, but all mineral
nutrients are chemical elements. Essential means that if you don’t have enough
copper in your body, you will die, because it’s absolutely necessary for human life. And micronutrient means it’s only needed
in small quantities. The average human only needs to eat about
900 micrograms of copper per day. That’s like, the weight of a small mosquito. Compare that to how much food you eat every
day. It’s a tiny amount! Copper in foods is usally not just floating
around as free copper atoms. Instead, copper atoms bind (in other words,
“connect”) to other atoms and form molecules, and often molecules bind to other molecules
and form chemical compounds. Ok, that’s it for chemistry 101. See? I promised you it was gonna be fast. Now let’s talk about healthy copper metabolism. Keep in mind that the human body is very complex
and I cannot explain right now every single thing about it. One, because there are many things the scientific
community doesn’t know for sure yet. And two, because if I told you everything
that we do know, this video would be like, days long. But I do wanna give you a simplified overview
so you can understand Wilson’s disease a little bit better. Anwyays, so first, you put the food in your
mouth, and in your mouth three things happen: 1, you use your teeth to chew on the food
to break it into smaller pieces; 2, you use your tongue to move the food around; and 3,
your salivary glands release saliva, which makes the food easier to swallow, and also
contains some enzymes that begin to break down large food chemical compounds into smaller
food molecules. Enzymes, by the way, are protein molecules
that kind of do stuff to other compounds and molecules in your body, like for example in
this case, breaking them into smaller pieces. Ok, so second, you swallow the food, it goes
down your esophagus to the stomach, and in your stomach two things happen: 1, the walls
of the stomach, which are made of muscle, contract and relax many times to move the
food around; and 2, your stomach releases gastric acid and more enzymes, to continue
to break down food compounds and molecules into smaller, more manageable pieces. A small amount of copper is absorbed in the
stomach. But let’s continue. Third, the food, which by now is very liquidy,
goes from the stomach to the small intestine, and in your small intestine three things happen:
1, the walls of the intestine contract and relax to keep mixing your food as it goes
down; 2, the gallbladder releases bile, which was originally made in the liver but got stored
in the gallbladder until it was needed for digestion; and 3, the pancreas releases pancreatic
juice. With the help of the bile and the pancreatic
juice, which have cool stuff like acids and even more enzymes, the food compounds and
molecules keep breaking down into smaller pieces. It is here in the small intestine where most
of the copper and other nutrients get absorbed into the bloodstream. And finally, fourth, the leftover stuff goes
to the large intestine, some more things happen, you go to the toilet, and you poop it out. I told you a minute ago that copper gets absorbed
a little bit in the stomach, but mainly in the small intestine. Absorption in this context means that it gets
taken from the digestive tract and brought into to the bloodstream. But how does it actually happen? Let’s zoom into this section of the small
intestine. These are the intestinal walls, and this is
the space where the food being digested travels towards its ultimate demise in the toilet
bowl. Let’s zoom in even further into this section
of the intestinal wall. The walls of your intestine, like most of
your body, are made of many cells. The top layer of cells is call the epithelium,
and epithelial cells are the only ones in your intestine that actually, physically touch
the food that’s being digested. And let’s zoom in one last time into one,
single epithelial cell. This upper side of its cellular membrane is
the one that actually comes in contact with the food. And here are several kinds of proteins that
transport copper ions across the cellular membrane to the inside of the cell. And I’m not talking about protein ATP7B,
these are different proteins encoded in different genes. So now that copper ions are inside these epithelial
cells, most of them have to travel from cell to cell until they make it to the small blood
vessels that are within the intestinal wall. The copper ions make this trip with the help
of, again, several types of proteins When the copper ions finally make it to the
blood, they get transferred to different molecules, including transcuprein and albumin, which
will carry them while they’re in the bloodstream. The blood in the tiny vessels all over your
small intestine gets collected into a large vein called the portal vein. The portal vein goes pretty much directly
to the liver, and there it branches out again into many smaller blood vessels. Here in the liver, copper gets transferred
from the carrier molecules in the blood to the liver cells that are touching the blood
vessels. And then it travels from liver cell to liver
cell, once again with the help of several types of proteins. So let’s now focus on protein ATP7B, which
is very important in the liver, and of course it’s very important to us when we’re talking
about Wilson’s disease. Let’s zoom in into one single hepatocyte,
which is the main type of cell in the liver. Even though hepatocypes are very small, usually
smaller than the thickness of a human hair, they have a lot going on inside. I don’t need to tell you right now about
all the parts of a hepatocyte, but I want to draw your attention to this structure over
here, called the Golgi apparatus, and specifically to this part of the Golgi apparatus called
the TGN, the trans-Golgi network. Many important things happen here at the TGN. One of them is that protein ATP7B loads copper
ions onto another protein called ceruloplasmin. Ceruloplasmin is the number one copper-carrying
molecule in human blood serum. Serum is the portion of blood that is neither
red blood cells nor the stuff that makes your blood clot. In healthy people, about 90% of serum copper
is being carried by ceruloplasmin, and the rest is floating around as free copper ions. So, as the blood circulates around the body,
ceruloplasmin molecules deliver it everywhere else. I will tell you more about ceruloplasmin when
we learn about the blood tests that are involved in diagnosing Wilson’s disease, but this
is enough for now. So going back to the hepatocytes in the liver. If the concentration of copper ions inside
a hepatocyte becomes too high, ATP7B protein molecules migrate from the TGN to the cellular
membrane and transport copper ions into liver bile. The bile gets collected and concentrated in
the gallbladder, and the next time you eat something, it will get released into the small
intestine. I told you earlier that bile helps digest
food in the small intestines, but what I didn’t tell you is that bile also carries some waste
products to the small intestine, and this includes the excess copper your body doesn’t
need. This way, most of your excess copper leaves
your body when you poop. Additionally, if you have some excess copper
in the blood, the kidneys can collect it and put it in the urine, so a small amount of
copper can leave your body when you pee. Phew! So that’s an overview of healthy copper
metabolism. Thankfully, now that you know all that, it
will be very easy for you to understand what happens if you have Wilson’s disease. So in this case most of the process is basically
the same. The big difference is that your ATP7B protein
molecules are not built in the right way, therefore they don’t work properly, therefore
they’re not able to transfer copper ions from hepatocytes to ceruloplasmin or bile
very well. As a result, copper ions are going into hepatocytes,
but they’re not leaving fast enough, so over time the concentration of copper ions
in the hepatocytes gets higher and higher and higher. When we have too many copper ions hanging
around inside a cell, the copper ions cause damage, and eventually the cell breaks apart. The broken cell releases a bunch of free copper
ions, which end up in the blood, which carries them all over the body. So these free copper ions end up accumulating
and causing damage in other places. And this is why Wilson’s disease patients
can have problems in many different organs, and not just the liver. See? That last part went really fast! And in any case I think you’ve had enough
for today. Next week I will continue the story by telling
you more about the symptoms of Wilson’s disease. If you learned something new today please
give me a thumbs up, and if you have any questions or comments you can find me on Facebook, Instagram,
Youtube, or by e-mail. My name is Cupri. See you there, Copperheads!


  1. hello my dear Cupri! This video was a little bit hard to understan, but I will ask my biology teacher to explain me and if i still have doubts i will ask you.Thank you!

  2. can you post the sources you used to make this video? i am doing a research on this topic and i used some information that was in the video and i would appreciate if you tell me about useful
    books you used to educate your self on this topic

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