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So many, many proteins inside our body are actually synthesized in their inactive form.
Modification of Amino Acids .txt
And some examples include digestive enzymes, for example, chimotrypsin, we have blood clotting enzymes.
Modification of Amino Acids .txt
Fibrin, we have hormones, for example, adrenal, corticotropic hormone, ACTH.
Modification of Amino Acids .txt
All these different types of hormones in our body are synthesized initially in their inactive state and to activate them, some type of enzyme, some type of catalyst basically cleaves a peptide bond.
Modification of Amino Acids .txt
And once we cleave that bond, we produce the active form of that protein.
Modification of Amino Acids .txt
So not only can we modify the amino acids of our proteins and thereby modify their functionality, we can also actually cleave specific peptide bonds within many different types of proteins, thereby activating those proteins.
Modification of Amino Acids .txt
And we'll see that in much more detail when we'll focus on these different types of enzymes and these different types of cellular processes.
Modification of Amino Acids .txt
Although our liver is responsible for the majority of the metabolism of amino acids that occurs inside our body, other organs and tissues can also break down amino acids and then use the carbon skeleton byproducts for energy.
Glucose-alanine cycle .txt
And one example of such a tissue is our muscle tissue.
Glucose-alanine cycle .txt
So if we're undergoing prolonged exercise or if we're fasting, our skeleton muscle tissue tissue can actually begin to break down branch chain amino acids such as valine, isolucine and leucine.
Glucose-alanine cycle .txt
And then we form carbon skeleton intermediates, and then those are used for energy purposes.
Glucose-alanine cycle .txt
But of course, every time we metabolize amino acids, we form nitrogen as a byproduct.
Glucose-alanine cycle .txt
More specifically, we form ammonium.
Glucose-alanine cycle .txt
And as this process continually takes place, we build up the amount of ammonia that is present inside our skeleton muscle cells.
Glucose-alanine cycle .txt
Now, ammonium is toxic, and so what the skeleton muscle cells must do is they must be able to dispose of that ammonium.
Glucose-alanine cycle .txt
Now, unlike in the liver, and to a smaller extent in the kidney, where we have the urea cycle to basically dispose of that ammonium inside the skeleton muscle cells, we don't actually have a way to dispose of ammonium directly.
Glucose-alanine cycle .txt
And that's because the urea cycle does not take place inside the muscle.
Glucose-alanine cycle .txt
And so our body actually has two ways by which it can get rid of this ammonium from our skeletal muscle.
Glucose-alanine cycle .txt
But ultimately, what the skeleton muscle cell must do is it must be able to transport that ammonium back to the liver, where that ammonium can be fed into the urea cycle.
Glucose-alanine cycle .txt
And one of these pathways is known as the glucose alanine cycle.
Glucose-alanine cycle .txt
And this will be the focus of this lecture.
Glucose-alanine cycle .txt
So let's suppose we are fasting.
Glucose-alanine cycle .txt
Eventually, we begin to break down the branch chain amino acids into the carbon scale intermediates, and then we form ammonium as a byproduct.
Glucose-alanine cycle .txt
Now, ammonium must be transformed into some other molecules.
Glucose-alanine cycle .txt
So we must have some type of carrier molecule that ultimately transports through the blood to the liver.
Glucose-alanine cycle .txt
So ammonium must be combined with Pyruvate.
Glucose-alanine cycle .txt
Now, where do we get the Pyruvate from?
Glucose-alanine cycle .txt
Well, inside our muscle, we have glycogen storages.
Glucose-alanine cycle .txt
We break down the glycogen to glucose, and we break down glucose into Pyruvate via glycolysis.
Glucose-alanine cycle .txt
So we generate ATP.
Glucose-alanine cycle .txt
That ATP can be used by the cell, and the Pyruvate can also be used to actually combine with ammonium to form glutamate, and then glutamate is transformed into aluminium.
Glucose-alanine cycle .txt
And actually, this is the reverse pathway that we discussed in the previous lecture.
Glucose-alanine cycle .txt
So previously we discussed how we can break down alanine into ammonium, but now we see how, under other conditions, we can actually do the reverse.
Glucose-alanine cycle .txt
We can take the ammonium combined with Pyruvate to ultimately form that alanine, and it's the alanine that is transported out of the cell into our bloodstream and that ultimately is absorbed by hepaticides, our liver cells.
Glucose-alanine cycle .txt
Now, once the alanine moves into the liver, the alanine basically undergoes this pathway.
Glucose-alanine cycle .txt
But in reverse.
Glucose-alanine cycle .txt
So we begin with Alanine.
Glucose-alanine cycle .txt
Alanine then is formed into glutamate, and then that breaks down into pyruvate and ammonium.
Glucose-alanine cycle .txt
So ultimately, what happened is the ammonium that we used here or that we formed here, eventually made its way to the liver.
Glucose-alanine cycle .txt
And it's the liver that uses the urea cycle to basically help our body dispose of this toxic substance.
Glucose-alanine cycle .txt
Also notice, though, that we form pyruvate and it's in the liver that we undergo gluconeogenesis.
Glucose-alanine cycle .txt
It's in the liver where we undergo gluconeogenesis.
Glucose-alanine cycle .txt
And so pyruvate is used to form glucose.
Glucose-alanine cycle .txt
And the glucose that we essentially used here is then transported back into the skeleton muscle via the bloodstream.
Glucose-alanine cycle .txt
So ultimately, even though we used a glucose here to form that pyruvate, and we used that to essentially attach that ammonium and then transported via the bloodstream via Alanine, the glucose is ultimately returned back to the skeleton muscle tissue.
Glucose-alanine cycle .txt
So all that happened here is we ultimately transported this ammonium to our liver.
Glucose-alanine cycle .txt
Now, this is known as the glucose Allenine cycle.
Glucose-alanine cycle .txt
We call it glucose Allenine because we utilize a glucose here to form pyruvate, to use it to actually attach that ammonium and form that alanine.
Glucose-alanine cycle .txt
That's why we call it the glucose Alanine cycle.
Glucose-alanine cycle .txt
It cycles between glucose and Alanine, but it's also returned back to its source, the skeleton muscle cell.
Glucose-alanine cycle .txt
But the ammonium is transported into the skeletal, into the liver.
Glucose-alanine cycle .txt
It's not returned back to the skeleton muscle.
Glucose-alanine cycle .txt
Now, so the glucose Alanine cycle is one pathway by which we can transport the ammonium from our target tissue, our skeletal muscle tissue, to our liver.
Glucose-alanine cycle .txt
But there is another method and that utilizes an enzyme known as glutamine synthetase.
Glucose-alanine cycle .txt
So glutamine synthetase is an ATP driven enzyme.
Glucose-alanine cycle .txt
It uses ATP to basically attach the ammonium that we formed here onto glutamate to form glutamine.
Glucose-alanine cycle .txt
And glutamine, just like Alanine, can move into the bloodstream, ultimately move into the hepatocytes, our liver cells, and then the glutamine can be broken down into glutamate releasing ammonium, and the ammonium can be fed into the urea cycle in the same exact way.
Glucose-alanine cycle .txt
So these are the two pathways, the methods by which, once we form the ammonium inside our skeletal muscle tissue, we can transport that ammonium into the liver, where the liver uses the urea cycle to basically dispose of that toxic substance.
Glucose-alanine cycle .txt
Before we discuss the process of translation in which we synthesize our proteins from RNA molecules we have to discuss a concept known as the genetic code.
The Genetic Code.txt
Now, as we'll see in just a moment, the genetic code is basically a system that is used by the cells specifically by the ribosomes to translate the language used by the RNA molecules molecules the language that is used by our proteins.
The Genetic Code.txt
And we'll see what that means in just a moment.
The Genetic Code.txt
First, let's discuss several other important points.
The Genetic Code.txt
So the central dogma of molecular genetics is basically a concept that tells us that the flow of genetic information in any cell goes from the DNA molecule to the RNA molecule to the protein.
The Genetic Code.txt
Now, any given DNA molecule in any given organism consists of genes and genes are basically specific sequences of nucleotides that code for proteins.
The Genetic Code.txt
Now, even though DNA molecules contain genes DNA molecules themselves are not directly used in protein synthesis.
The Genetic Code.txt
What happens is our DNA molecules, the genes in DNA molecules are transcribed into RNA molecules.
The Genetic Code.txt
So we basically transfer the genetic information from our DNA to our RNA and then those RNA molecules are used by ribosomes to basically form our proteins by using the genetic code as we'll see in just a moment.
The Genetic Code.txt
So it's not the DNA but it's the RNA molecules that is directly involved in the process of translation in the process of protein synthesis.
The Genetic Code.txt
Now, the entire sequence of DNA of any organism including the genes as well as the non coding regions of our DNA is known as the genome.
The Genetic Code.txt
And only a small percentage of the genome actually consists of the coding regions of the regions of nucleotides that code for proteins.
The Genetic Code.txt
And that's exactly why we have to use these RNA molecules because the DNA molecules consist predominantly of non coding regions.
The Genetic Code.txt
So one reason why we use the process of transcription is to basically only transcribe the genes into our RNA molecules so that we don't have to worry about the non coding regions about the non coding regions that basically do not code for any protein.
The Genetic Code.txt
Now let's recall what the process of transcription is.
The Genetic Code.txt
So as we mentioned earlier, the process of transcription is pretty simple and that's because both RNA and DNA molecules are polymers of the same exact units of the same exact molecule known as the nucleotide.
The Genetic Code.txt
The only difference between the nucleotides of RNA and DNA molecules is that in DNA the sugar is the deoxyribose and in RNA the sugar is the ribose and in RNA the thymine are replaced with the uracil nitrogenous bases.
The Genetic Code.txt
So let's take a look at the following diagram.
The Genetic Code.txt
So let's suppose we have the following DNA molecule that we want to use as the template for transcription.
The Genetic Code.txt
And this DNA molecule is commonly known as the antisense strand or the antisense strand.
The Genetic Code.txt
So basically the antisense strand consists of our adenine cytosine adenine and thymine nucleotides.
The Genetic Code.txt
So when transcription takes place our cell transcribes beginning on the three end and ending at the five end, so that we transcribe the new RNA beginning at the five and ending at the three end.
The Genetic Code.txt
And the method by which we actually transcribe is pretty simple, because the language that is used by RNA and DNA is exactly the same.
The Genetic Code.txt
That is, both of these molecules use nucleotides.
The Genetic Code.txt
So when transcribing from DNA to RNA, we synthesize RNA by using the nucleotides that are complementary to the nucleotides on the antisense DNA strands.
The Genetic Code.txt
So basically, if this is A, then we know this must be you.
The Genetic Code.txt
If this is cytositosine, this must be guanine.
The Genetic Code.txt
If this is adenine, this must be uracil.
The Genetic Code.txt
And if this is thymine, then this must be adenine, and so forth.
The Genetic Code.txt
So basically, when in the nucleus transcription takes place, the cell has no problem transcribing from our DNA to our RNA, because all it has to do is find the complementary nucleotide.
The Genetic Code.txt
But during the process of translation, when we synthesize our proteins from RNA molecules, things aren't that simple.
The Genetic Code.txt
And that's because our mRNA consists of nucleotides.
The Genetic Code.txt
So the language of RNA is the language of nucleotides, but proteins use the language of amino acids.
The Genetic Code.txt
And as we know, nucleotides and amino acids are not the same type of molecules.
The Genetic Code.txt
So the question is, how exactly does the cell know what sequence of nucleotides corresponds to a sequence of amino acids?
The Genetic Code.txt
So once again, things become a bit more complicated when we synthesize proteins during the process of translation, which we'll discuss in much more detail in the next several lectures.
The Genetic Code.txt
So, in translation, the mRNA molecule, which itself is composed of nucleotides, is used as a template to synthesize our proteins that consist of amino acids.
The Genetic Code.txt
And here lies our problem.
The Genetic Code.txt
Nucleotides are different from amino acids, so we cannot use this complementary method.
The Genetic Code.txt
So how exactly does the cell know what sequence of nucleotides corresponds to what sequence of amino acids?
The Genetic Code.txt
So what the cell actually does is it translates the language of our nucleotides, our mRNA molecule, to the language of our proteins, our amino acids, by using a system known as the genetic code.
The Genetic Code.txt
So basically, the ribosomes of the cell use our RNA molecule, use our genetic code to translate the sequence of nucleotides in the mRNA molecule to the sequence of amino acids.
The Genetic Code.txt