Chapter 18 Amino Acid Oxidation and the Production of Urea in Part II Bioenergetics and Metabolism

Chapter 18 AMINO ACID OXIDATION AND THE PRODUCTION OF UREA

An illustration depicts the chapter opener

We now turn our attention to the amino acids, the final class of biomolecules that, through their oxidative degradation, make a significant contribution to the generation of metabolic energy. The fraction of metabolic energy obtained from amino acids, whether they are derived from dietary protein or from tissue protein, varies greatly with the type of organism and with metabolic conditions. Carnivores consume primarily protein and thus must obtain most of their energy from amino acids, whereas herbivores may fill only a small fraction of their energy needs by this route. Most microorganisms can scavenge amino acids from their environment and use them as fuel when required by metabolic conditions. Plants, however, rarely if ever oxidize amino acids to provide energy; the carbohydrate produced from ${CO}_{2}$ $CO Subscript 2$ and $H_{2} O$ $upper H Subscript 2 Baseline upper O$ in photosynthesis is generally their sole energy source. Amino acid concentrations in plant tissues are carefully regulated to just meet the requirements for biosynthesis of proteins, nucleic acids, and other molecules needed to support growth. Amino acid catabolism does occur in plants, but only to produce metabolites for other biosynthetic pathways.

Amino acid oxidation pathways can seem complex, and they are best understood in the context of five principles:

The many paths for amino acid catabolism have two broad parts, one involving the amino groups and the other involving the carbon skeletons. All of the pathways for amino acid degradation include a key step, always involving a pyridoxal phosphate cofactor, in which the α-amino group is separated from the carbon skeleton and shunted into the pathways of amino group metabolism. The carbon skeletons are broken down to citric acid cycle intermediates (Fig. 18-1).
Four amino acids — alanine, glutamate, glutamine, and aspartate — play key roles in the transport and distribution of amino groups. All are present in relatively high concentrations in one or many mammalian tissues. All are readily converted to key citric acid cycle intermediates.
Metabolic pathways are not distinct. The various pathways for amino acid catabolism are elaborately intertwined with other catabolic and anabolic pathways.
Free ammonia is toxic. Excess amino groups must be safely excreted. In mammals, the urea cycle serves this purpose.
Each amino acid has a different catabolic fate. The varied carbon skeletons of amino acids are broken down via equally varied pathways. All can be oxidized to generate ATP. All but leucine and lysine can contribute to gluconeogenesis when needed.

A figure shows the interactions of major reactions involved in amino acid catabolism in mammals. — FIGURE 18-1 Overview of amino acid catabolism in mammals. The amino groups and the carbon skeleton take separate but interconnected pathways.

Intracellular protein is shown at the top with upward- and downward-pointing arrows beneath, indicating a reversible reaction that yields amino acids. Dietary protein on the left has an arrow pointing right to amino acids. Two arrows point down from amino acids, one that bends left to N H 4 plus and one that bends right to carbon skeletons. N H 4 plus begins reactions that lead to the urea cycle and carbon skeletons begin reactions that lead to the citric acid cycle. From N H 4 plus, an arrow points downward. Just below N H 4 plus, an arrow branches off to the left to point to biosynthesis of amino acids, nucleotides, and biological amines before the main arrow branches slightly left to point to carbamoyl phosphate. An arrow points down from carbamoyl phosphate to join the Urea cycle just before the twelve o’clock position. This arrow ends just past the twelve o’clock position, where it meets an arrow that runs clockwise to the five o’clock position. An arrow runs clockwise from the five o’clock position to just before the twelve o’clock position, where carbamoyl phosphate joins the cycle. Just past the six o’clock position, an arrow branches off and points to urea (nitrogen excretion product). The urea cycle is the left-hand cycle of a horizontal row of three adjacent cycles. The central cycle, labeled aspartate-arginino-succinate shunt of citric acid cycle, has a counterclockwise arrow that runs from the twelve o’clock position to touch the urea cycle at the nine o’clock position and end at the six o’clock position, where it meets a similar counterclockwise arrow that runs from the six o’clock position to touch the citric acid cycle at the three o’clock position before ending at the twelve o’clock position. The citric acid cycle has a clockwise arrow that begins at the one o’clock position, as alpha-keto acids are added to the cycle, and runs clockwise around the entire circle. Two arrows branch off from this cycle: an arrow branches from the three o’clock position to C O 2 plus H 2 O plus A T P and an arrow branches from just past the six o’clock position to oxaloacetate, from which a vertical arrow points down to glucose (synthesized in gluconeogenesis). The alpha-keto acids that enter the citric acid cycle are derived from carbon skeletons produced from amino acids near the top of the figure. The amino acids produced from intracellular protein at the start of the figure yield N H 4 plus and carbon skeletons, and an arrow points down from carbon skeletons to the alpha-keto acids that enter the citric acid cycle. All data are approximate.

In mammals, blood glucose must be supplemented by gluconeogenesis, often just a few hours after a meal. Amino acids, particularly alanine and glutamine, can make a significant contribution to the fuel for gluconeogenesis. Amino acids undergo oxidative degradation in three different metabolic circumstances:

Amino acids released during normal protein turnover are not needed for new protein synthesis.
Ingested amino acids exceed the body’s needs for protein synthesis.
Cellular proteins are used as fuel because carbohydrates are either unavailable or not properly utilized due to starvation or uncontrolled diabetes mellitus.

The pathways of amino acid catabolism are quite similar in most organisms. The focus of this chapter is on the pathways in vertebrates, because these have received the most research attention. As in carbohydrate and fatty acid catabolism, the processes of amino acid degradation converge on the central catabolic pathways, with the carbon skeletons of most amino acids finding their way to the citric acid cycle. In some cases, the reaction pathways of amino acid breakdown closely parallel steps in the catabolism of fatty acids (see Fig. 17-9). We begin with amino group metabolism and nitrogen excretion, before turning to the fate of the carbon skeletons derived from the amino acids; along the way we see how the pathways are interconnected.