Urea cycle; oxidative phosphorylation 1

Published on April 19, 2020 Reviewed on November 27, 2022   28 min

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0:00
Greetings. Welcome to this Principles of Biochemistry lecture series. I am Jerry Feigenson, a Professor in the Department of Molecular Biology and Genetics at Cornell University in the USA. In the 17th lecture, you learned that the pyruvate end product from glycolysis has several possible fates, including in the mitochondrial matrix where it can form acetyl-CoA that enters the citric acid cycle. Then we discussed fats in the diet and metabolism of fatty acids and ketone bodies.
0:42
In this 18th lesson, you will learn that amino acids as fuel behave differently from carbohydrates or fatty acids as fuel. The nitrogen from amino acid breakdown must be converted to a non-toxic form, which is urea. You will see the mitochondrial electron transport chain, where the various fuels create a gradient of protons and voltage across the inner mitochondrial membrane. In the second part, you will see four different protein complexes that make up the mitochondrial electron transport chain. And finally, we will look at the ATP synthase enzyme which uses this gradient to catalyze ATP synthesis.
1:32
Let's look at amino acid breakdown. Amino acids can be used as fuel, but we have to pay attention to that Alpha-amino group. So amino acids as the last type of fuel to consider, they're about 10 percent of the fuel in our diet. We can compare amino acids to other fuel molecules. For example, fatty acids in excess of the need for energy or synthesis they have a special storage form, and that is as fat. And then sugar. Sugar in excess of our need for energy or synthesis has its own special storage form, that is as glycogen. But amino acids are different. Amino acids in excess of our need for fuel or synthesis, there is no storage form as either amino acids or as protein. And instead, when amino acids break down, first, the Alpha-amino group is removed. We get rid of it as urea, and what's left over, we call the carbon skeleton, and that becomes a useful metabolite. Let's see how this works. The overall general form of amino acid break down, and we'll use a green R to indicate the residue for any amino acid. So we have on the left a generic amino acid, that reacts with Alpha-ketoglutarate in the active site of an enzyme called an amino transferase. So here, the amino transferase is clearly shown to be an enzyme, and that yields an Alpha-keto acid and glutamate. So this is the general form for amino acid break down. Let me show you two specific examples. The first one is with amino acid aspartate, so aspartate breakdown. Aspartate in the active site of an amino transferase reacts with Alpha-ketoglutarate. It's an amino transferase. In effect, the amino group is switched for a ketone group. In the case of aspartic acid, the amine group leaves, a ketone group replaces it, this makes oxaloacetate, and a glutamate is the other product. Let's look at one other case. Here is alanine. The amino acid alanine reacts in the active site of another amino transferase with Alpha-ketoglutarate. That reaction yields, well, the switch between a ketone and an amino, that yields pyruvate and glutamate. So we see that there's a special role for Alpha-ketoglutarate. It's reacting with these amino acids, and there's a key role for glutamate, this is a product of these amino transferase reactions. Now, these occur for 18 of the 20 amino acids and proteins. The two exceptions form ammonia more directly. Serine breaks down, there is actually another step not shown here, breaks down to pyruvate and an ammonium ion, and threonine breaks down to Alpha-ketoglutarate and an ammonium ion. What happens to that ammonia?