Protein Catabolism Biochemistry PDF

# Protein Catabolism ## Introduction Proteins are not the primary source of energy for most organisms because proteins serve important biological roles as enzymes, transport systems, structural units, and more. However, under conditions of starvation an organism may digest its own proteins for ene...

# Protein Catabolism ## Introduction Proteins are not the primary source of energy for most organisms because proteins serve important biological roles as enzymes, transport systems, structural units, and more. However, under conditions of starvation an organism may digest its own proteins for energy, and even under well-fed conditions a basal level of protein digestion and recycling occurs. Proteins obtained through the diet are also broken down into their constituent amino acids to be used for synthesis of other proteins needed by the body. An abundance of protein digestion products in the blood or urine may indicate malnutrition or various disease states. This lesson describes the means by which proteins are digested into individual amino acids, and the mechanisms by which amino acids may be digested for energy or other purposes. ## 13.2.01 Protein Degradation Protein catabolism begins with degradation of proteins into short peptides or individual amino acids. Protein obtained through the diet is digested by various proteases found throughout the digestive tract, including pepsin, trypsin, chymotrypsin, and carboxypeptidase. The amino acids and short peptides produced in the digestive tract are absorbed by intestinal cells (Figure 13.27), and the short peptides are further digested to amino acids and allowed to enter the blood stream. The amino acids are then transported to various tissues throughout the body where they can be incorporated into the proteins needed by those tissues. ## 13.2.02 Transamination, Deamination, and Deamidation The first step in the catabolism of many amino acids is transamination, in which the α-amino group of an amino acid is transferred to another molecule such as α-ketoglutarate. This process converts the amino acid into a form called an α-keto acid, which has a ketone group where the α-amino group previously was. α-Ketoglutarate becomes glutamate when it receives the amino group, as shown in Figure 13.28. ## 13.2.03 The Urea Cycle Once in the liver, both glutamate and glutamine are transported to the mitochondria, where they are deamidated (glutamine) and deaminated (glutamate) to produce ammonium ions (which are in equilibrium with ammonia). In humans and many other terrestrial (i.e., land-dwelling) animals, these ammonium ions and ammonia molecules then enter the urea cycle. The details of the urea cycle (shown in Figure 13.32) are unlikely to be tested on the exam, but study of the urea cycle helps highlight the interplay between different metabolic pathways (e.g., the citric acid cycle). Defects in the urea cycle can lead to severe metabolic disorders with effects ranging from chronic vomiting to impaired brain function to death. ## 13.2.04 Glucogenic and Ketogenic Amino Acids This lesson's discussion of amino acid catabolism has so far been limited to the handling of nitrogen. After an amino acid has lost its nitrogen atoms through deamination or deamidation, the carbon skeleton remains. Different amino acids produce different carbon skeletons, which are metabolized by distinct pathways. The pathways of degradation for most amino acids are unlikely to be tested on the exam, but a few trends are noteworthy. Specifically, amino acids may be glucogenic (i.e., precursors to gluconeogenesis), ketogenic (i.e., precursors to acetyl-CoA and ketone body formation), or both. Table 13.2 summarizes these amino acid groups. | Glucogenic only | Both glucogenic and ketogenic | Ketogenic only | |---|---|---| | Alanine, A | Phenylalanine, F | Leucine, L | | Cysteine, C | Isoleucine, I | Lysine, K | | Aspartate, D | Threonine, T | | | Glutamate, E | Tryptophan, W | | | Glycine, G | Tyrosine Y | | | Histidine, H | | | | Methionine, M | | | | Asparagine, N | | | | Proline, P | | | | Glutamine, Q | | | | Arginine, R | | | | Serine, S | | | | Valine, V | | | Glucogenic amino acids are those whose carbon skeletons can be converted to pyruvate or a citric acid cycle intermediate. Pyruvate can be converted directly to oxaloacetate as part of the gluconeogenesis pathway, and citric acid cycle intermediates can also be converted to oxaloacetate through the cycle. Oxaloacetate can then be converted to phosphoenolpyruvate by the enzyme PEPCK, which can continue through gluconeogenesis to generate glucose. Most of the proteinogenic amino acids are glucogenic only. Note that although pyruvate theoretically can become acetyl-CoA, protein and amino acid catabolism primarily occurs during fasting. Under this condition, gluconeogenesis in the liver is generally upregulated and pyruvate dehydrogenase is downregulated. Consequently, pyruvate is primarily used for gluconeogenesis during protein catabolism, and alanine, serine, glycine, and cysteine (each of which can become pyruvate) are not considered ketogenic. Although the specific pathways of glucogenic amino acid catabolism do not need to be memorized, an overview is provided in Figure 13.34. Ketogenic amino acids are those whose carbon skeletons can be converted to acetyl-CoA or to acetoacetyl-CoA. Under fasting conditions, these generate ketone bodies. This pathway is not glucogenic because, as described elsewhere, acetyl-CoA can be converted to oxaloacetate only by first reacting with oxaloacetate, and therefore no net increase in oxaloacetate occurs. Two amino acids, lysine and leucine, are ketogenic only. The remaining amino acids are both glucogenic and ketogenic because their carbon skeletons are split during catabolism. Some portions of the skeleton are glucogenic while others are ketogenic. These amino acids are tryptophan, phenylalanine, tyrosine, isoleucine, and threonine. These amino acids may be remembered using the mnemonic "FITTT" because "F"-enylalanine, isoleucine, and all of the amino acids that start with T are in this category. Figure 13.35 shows an overview of ketogenic amino acid catabolism, including amino acids that are also glucogenic.