Amino Acid Oxidation 1 - Online Tutor, Practice Problems & Exam Prep

Amino acid oxidation involves the conversion of amino acid carbon skeletons into energy via the citric acid cycle. Before this, nitrogen must be processed through the urea cycle in the liver, which consumes 3 ATP and produces urea. The cycle begins with the formation of carbamoyl phosphate from bicarbonate and ammonium, followed by the synthesis of citrulline and argininosuccinate. Ultimately, arginine is converted to urea and ornithine, which re-enters the mitochondria, allowing the cycle to repeat. This process is crucial for maintaining nitrogen balance and energy production in cells.

Amino Acid Oxidation 1

Let's begin by talking about amino acid oxidation, which is how the body uses the carbon skeletons from amino acids to fuel the citric acid cycle. Now, before it can use those amino acid carbon skeletons, it needs to do something about the nitrogens. It needs to get rid of them, but it can't just cut them off and release them as ammonia to the cell because that would really mess with the cell's pH and also it could be toxic to the cell. It's a reactive species. Anyhow, what the cell is going to do is it's going to take those nitrogens and it's going to put them through the urea cycle, which is a cycle that occurs in the liver, so it's going to export this stuff to the liver, and the cycle takes in 2 nitrogens and puts out 1 urea, and it costs 3 ATP to do this. So we're going to take a look at the cycle right here, and the first step, or what you could think of as the first step, which is right here, is going to occur inside the mitochondria. So this here is inside the mitochondria matrix. And out here, we have the cytosol. And what's going to happen is Carbamoyl Phosphatesynthetase, this enzyme right here, is going to take bicarbonate and this should be an ammonium because it's dissolved in the cell. So this figure is a little mistake. But you can see that up here that it's ammonium. And it's going to take bicarbonate and ammonium and at the cost of 2 ATP form this molecule right here, which is carbamoyl phosphate. I'm just going to write carbamoyl P. It's carbamoyl phosphate. Now, ornithine is going to enter the mitochondria. And ornithine is this molecule right here. That's ornithine. It's going to enter the mitochondria and it is going to combine with carbamoyl phosphate, and that phosphate group is going to leave. You can see it's inorganic phosphate, and they're going to combine to form this molecule right here, citrulline. Now, citrulline is actually going to then exit the mitochondria. So a little back and forth in here. It's going to exit the mitochondria, and then things get a little interesting. What's going to happen is ATP is going to be broken down to pyrophosphate. Of course, pyrophosphatase is going to break this down to 2 inorganic phosphates. And citrulline is going to be combined with aspartate. What's actually happening, you see this AMP let me jump out of the image here. My head is blocking it. You see this AMP right here. Basically, the AMP gets attached to the enzymatic intermediate. The aspartate is added, and the AMP leaves. So that's why you see the AMP coming off, a little later here before that pyrophosphate. So these come together and they form this molecule right here, argininosuccinate. Alright. Oh, I'm sorry, I'm not labeling my steps. So, we had step 1, this here was step 2 and this was step 3. Okay. So argininosuccinate is then cleaved into fumarate right here, and arginine right here. That is step 4. From there, arginine has urea removed from it, right? So basically, these nitrogens right here are coming off as urea and what we're left with is ornithine again right here. So that is our final step of the cycle, Step 6. And then, of course, that ornithine will reenter the mitochondria combined with carbamoyl phosphate, and the cycle will repeat itself. So, let's turn the page.

Here’s what students ask on this topic:

What is the role of the urea cycle in amino acid oxidation?

The urea cycle plays a crucial role in amino acid oxidation by removing excess nitrogen from amino acids. When amino acids are broken down for energy, their nitrogen atoms must be safely excreted to avoid toxicity. The urea cycle, occurring in the liver, converts these nitrogen atoms into urea, which is then excreted in urine. This cycle consumes 3 ATP molecules and involves several steps, including the formation of carbamoyl phosphate, citrulline, and argininosuccinate. Ultimately, arginine is converted to urea and ornithine, allowing the cycle to repeat. This process is essential for maintaining nitrogen balance and preventing the accumulation of toxic ammonia in the body.

How does the urea cycle start and what are its key steps?

The urea cycle starts with the formation of carbamoyl phosphate from bicarbonate and ammonium, catalyzed by carbamoyl phosphate synthetase I, consuming 2 ATP. This occurs in the mitochondrial matrix. Carbamoyl phosphate then combines with ornithine to form citrulline, which exits the mitochondria. Citrulline combines with aspartate, forming argininosuccinate, which is then cleaved into fumarate and arginine. Arginine is subsequently converted to urea and ornithine. The ornithine re-enters the mitochondria to continue the cycle. This process is vital for detoxifying ammonia and maintaining nitrogen balance in the body.

Why is ammonia toxic to cells, and how does the urea cycle mitigate this toxicity?

Ammonia is toxic to cells because it can disrupt cellular pH and interfere with metabolic processes. High levels of ammonia can lead to alkalosis and damage cellular structures. The urea cycle mitigates this toxicity by converting ammonia into urea, a less toxic compound that can be safely excreted in urine. This conversion occurs in the liver and involves several enzymatic steps, ensuring that ammonia is efficiently removed from the bloodstream and preventing its accumulation in tissues.

What is the energy cost of the urea cycle, and why is it necessary?

The urea cycle consumes 3 ATP molecules per cycle. This energy cost is necessary to drive the biochemical reactions that convert toxic ammonia into urea. The initial formation of carbamoyl phosphate from bicarbonate and ammonium requires 2 ATP, and the subsequent steps involve additional ATP consumption. Despite the energy expenditure, the urea cycle is essential for detoxifying ammonia, maintaining nitrogen balance, and preventing the harmful effects of ammonia accumulation in the body.

How are the carbon skeletons of amino acids used in the citric acid cycle?

After the removal of nitrogen via the urea cycle, the carbon skeletons of amino acids can be used in the citric acid cycle for energy production. These carbon skeletons are converted into intermediates such as pyruvate, acetyl-CoA, or other citric acid cycle intermediates. Once integrated into the cycle, they undergo oxidation to produce ATP, NADH, and FADH₂, which are essential for cellular energy. This process allows the body to utilize amino acids as an energy source, especially during periods of fasting or intense exercise.