01.08 Protein Metabolism

Hey there today. We’re going to talk about protein metabolism. The basic idea we’re going to talk about is how proteins get broken down into amino acids and then how they get built back up into proteins. Proteins can get broken down and they get broken down into amino acids. Now some amino acids can get synthesized, so we’re not just using amino acids that we get from our diet, but we can also make some--we’ll talk about those. And then in the end, amino acids are going to get used to create new proteins. Let’s talk a little bit about what proteins are. I often like to draw proteins as being kind of like a little blob. They’ve got an N-terminus and a C-terminus. Where that comes from is if we were to look at the chemical structure inside the middle of the protein, it would have this pattern: it goes nitrogen to what we call the alpha carbon, then carbonyl. And then that gets repeated over and over again: nitrogen alpha carbon, carbonyl. And then we have to put a little H’s off of our nitrogens. We’re just looking in the middle here, so this would just, continue on and on. Off of those alpha carbons, that’s where we have the side chains. So that’s where the R groups are. And remember, those can really vary a lot. You can have different sizes and shapes and charges and that sort of thing. So here’s the protein with its N-terminus and its C-terminus, and then here’s our peptide in the middle. That’s got an N-side to it and a C-side to it. So the carbonyl over here is what we refer to as the C. And if we were to look at just an individual amino acid--that’s what’s going to happen when this protein gets broken down--an amino acid looks like this: it has an NH3+ at one end and then would have an acid group (COO-) at the other end of it. And again, here’s that alpha carbon with the side chain coming off of it. So that nitrogen, in this case, we’ve got four bonds around it and that’s why it’s got a + (charge). And so it is a zwitterion...with a + and a -, with the amino (NH3+) on this side and this is the acid (COO-) on that side. That’s why it’s called an amino acid. Proteins are going to get unraveled and then broken down into amino acids. And then amino acids are going to be the building blocks then for synthesis of bigger proteins that our bodies need to function. The breakdown of dietary protein happens in our stomachs and it does this because we have a super acidic environment in there. There’s lots of HCl in the stomach. And so it’s got a very low pH and what that does is it helps to take that wound-up protein and unravel it into just a big, long strand like that. And then, in addition, there are things called proteases. Proteases are going to come along and break that protein up into chunks. Some of the proteases have very specific sequences that they will do the chopping after. For example, one you may have heard of trypsin. Trypsin cuts after positive residues, so if you’ve got a lysine or an arginine...those guys are positively charged, even at neutral pH they would be. Trypsin is going to cut right after those, and it breaks the protein up into little chunks. There are lots of other proteases. Chemotrypsin is another one that cleaves after a big bulky residues. But then there’s going to be other proteases that come along and just kind of chew up the protein so that you can get to that point that you just have those little single amino acids. The amino acids are then used to create new proteins and that happens through a process called translation. We will talk about that in a little bit. Before doing that, though, I’d like to talk a bit about amino acids and put them into some categories. The categories that we normally put amino acids into would be based on their size, shape, charge, if they’re neutral, positive, negative, that sort of thing. But what I’ve done is something a little bit different here. Here’s the 20 amino acids and I’ve got them with their three-letter codes and their one letter codes. And I put them into categories called 'essential', 'conditional', and 'non-essential'. Now it’s a little bit of a misnomer here because all amino acids are essential...we need all 20 of them. However, what a nonessential means...we can make them. Our bodies can synthesize the non-essential. And the truth is actually we can make the conditional ones, but only under certain conditions. Not everybody makes these amino acids here to a level that they would need to, so they would need to get them from their diet instead...or maybe you’re under a certain circumstances like during famine or something, or under certain health conditions...you might not be able to make these as well as you could. So there are reasons why these guys are considered conditional. But we should be able to make them we have the genes to make the enzymes to make these things. Now essential over here is what we need to eat. These guys: Need to Eat. That’s what the definition of essential is. You cannot make it so you need to eat it...you have to get it from your diet. Let’s talk about the ones that we can synthesize in our body. So remember, these are going to be the non-essential and the conditional ones...we can make these guys in our bodies. One of the things I want you to notice is that they come from familiar pathways: pentose phosphate pathway--maybe not super familiar--but this is the pathway that can take a glucose and make a ribose from it, and it also generates NADPH (it’s a totally nice bonafide metabolic pathway). Similarly, glycolysis...we’ve got glucose getting split in order to create pyruvate, and then that pyruvate can turn into acetylCoA as it goes into the citric acid cycle. These things are color coded in this diagram, showing that metabolites can get siphoned off from these pathways in order to create amino acids. Let’s say for example, pyruvate here can be used to create alanine, valine, isoleucins and leucine. Similarly there’s metabolites around the citric acid cycle. Those can get pulled out and then turned into things like glutamate, glutamine, proline, arginine. These are those different conditional and non-essential amino acids that can get made through metabolic processes in our body. And just remember, the other ones are the essential ones, and those are the ones that we need to eat. Now let’s look at how protein synthesis happens. So protein synthesis....that’s what translation is. So we’ve got this awesome, beautiful structure here. Let’s focus in first on the messenger RNA down here. That’s what this strand is. This messenger RNA is going to come from reading genes. The DNA is going to get transcribed into RNA, and then RNA is going to get turned into protein. This is the 'central dogma' right here. This is called transcription and I’ll abbreviate that as just TXN. This one down here is translation. That’s what this is a picture of. TNL is my way of abbreviating translation. If you need to express a certain gene and turn it into protein, then this is the process that your body is going to go through. It would first make a transcript of the gene, and that’s what this messenger RNA is here.

This big green thing here...this is the ribosome, and it is mostly made of ribosomal RNA. That ribosomal RNA also comes from expression of ribosomal DNA genes. So it makes a ribosomal RNA. There are proteins in here, but interestingly enough, it is the RNA that is the catalytic part of it. So here where the actual chemistry takes place, there aren’t even any proteins close to this place. It is all catalyzed by the RNA sequences--which I think is super cool. Also really neat are these little molecules here tRNAs....tRNAs are adapter molecules. If you notice down at this end here, you can imagine here that there are three nucleotides...three bases are actually reaching out into the air here. Those are going to pair with the three letter code in the messenger RNA. You’ll notice these things are put in threes...three pinks, three pinks, three blues, et cetera. Well, these three things here are an anticodon and these three here are a codon. They’re going to match with each other. They’re going to just base pair, same base pairing that you would see in a DNA double helix. And the cool part is that there is an amino acid that is going to be coordinated to the particular anticodon that’s down here. And so what that does...is it allows the messenger RNA to indicate what amino acid should be coming in here into the active site. These three bases down here that are the codon match with these of the anticodon because it said, "Hey, bring this particular amino acid into the active site and get it linked onto the growing peptide that’s coming out of the ribosome". So that’s pretty much how translation works. We create this protein based on those individual amino acids that are dictated by the sequence of the messenger RNA.

Alright, let’s summarize. Dietary protein is going to get unraveled and broken up by the action of the HCl and the proteases that are in your stomach. If you’re not eating all of the different amino acids that you need, some of them could be made through biochemical reactions that would evolve metabolites from pentose phosphate pathway, glycolysis, or citric acid cycle--you could create new amino acids that way. And then these amino acids together are going to come and get attached to a tRNA. Then the code that’s dictated by the DNA...getting transcribed into a messenger RNA...all of that catalysis this can take place in the ribosome to link those little amino acids together to create a new protein that could go on and do neat things in your body. Alright, we love you guys! Go out and be your best self today, and as always happy nursing!