Amino Acid Degradation

Abstract

Amino acids are valuable metabolic fuels, providing a supply of both nitrogen and carbon for intermediary metabolism and energy for growth. Controlled degradation of amino acids is important in the maintenance of the carbon–nitrogen balance. It is becoming increasingly apparent that imbalance in amino acid degradation can have important consequences for both development and disease. Generally, the first step in degradation of amino acids results in the amino group either being incorporated into other nitrogenous compounds or being excreted as ammonia or urea, while the carbon skeleton is catabolised to one of a few common metabolic intermediates. Thus, an understanding of amino acid degradation provides knowledge of the interrelationships between metabolic pathways and helps explain some of the clinical features when deficiencies in amino acid metabolism occur.

Key Concepts

  • Amino acids are important growth substrates for microorganisms.

  • Tight control of amino acid degradation and cycling maintains the C–N balance.

  • Glutamate is a key central amino acid in maintenance of the C–N balance.

  • The first step in amino acid degradation is removal of the α‐amino group.

  • Key steps in amino acid degradation include deamination, catalysed by pyridoxal‐phosphate‐dependent transaminases, oxidoreductases or carbon–oxygen lyases, decarboxylase reactions and carbon skeleton rearrangements catalysed by isomerases.

  • Carbon skeletons arising from amino acid breakdown are channelled into central metabolism.

  • Production and excretion of urea and uric acid by animals and birds and reptiles, respectively, avoids the accumulation of toxic levels of ammonia in blood and tissues.

  • Metabolic products derived from l‐serine are essential for cell proliferation and a functional nervous system.

  • Absence of key enzymes, or imbalance in amino acid degradation, leads to severe disease states, such as phenylketonuria and methylmalonic aciduria.

Keywords: amino acids; metabolism; urea cycle; pyridoxal phosphate; inborn errors in metabolism

Figure 1. Overview of the metabolic fate of amino acids during degradation.
Figure 2. Summary of the reactions involved in removal of the α‐amino group from amino acids. Each reaction is depicted using a generic amino acid, with the exception of elimination, where the amino acid can be either serine or threonine.
Figure 3. Mechanism of action of pyridoxal phosphate in enzyme catalysis. The first half of a transamination reaction is depicted. In the first part of the reaction, pyridoxal phosphate is shown to be linked via Schiff base (internal aldimine) to a lysine residue on the polypeptide backbone. The arrows directed towards the three bonds of the α‐carbon of the amino acid linked to PLP (external aldimine) indicate the cleavages that can occur in different enzymes. Examples of enzymes catalysing these reactions include, for aldol cleavage, serine hydroxymethyltransferase; for transamination, aspartate aminotransferase and for decarboxylation, arginine decarboxylase.
Figure 4. Mechanism of the glycine reductase complex. The glycine reductase (GR) complex comprises proteins A, B and C. Glycine forms a Schiff's base with enzyme B, allowing nucleophilic attack by the Se anion forming a carboxymethylselenocysteine directly linked to protein A. Thiotransfer to a cysteinyl of protein C results in acetylcysteine and subsequent cleavage in the presence of inorganic phosphate release acetyl phosphate. Thioredoxin (Trx) re‐reduced the Se–S on protein A.
Figure 5. The urea cycle. The link between the urea cycle and intermediary metabolism through the TCA cycle is shown. Enzymes: (1) transaminases; (2) glutamate dehydrogenase; (3) carbamoyl phosphate synthetase; (4) ornithine carbamoyltransferase; (5) argininosuccinate synthetase; (6) argininosuccinase; (7) arginase; (8) fumarase and (9) malate dehydrogenase.
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Further Reading

Berg JM, Tymoczko JL and Stryer L (2010) Biochemistry, 7th edn. New York: Freeman.

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Schauder P, Wahren J, Paoletti R, Bernardi R and Rinetti M (eds) (1992) Branched‐Chain Amino Acids: Biochemistry, Physiopathology and Clinical Sciences. New York: Raven Press.

Valle D, Beaudet AL, Vogelstein B, et al. (eds) (2006) The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw‐Hill.

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Sawers, R Gary(Jan 2015) Amino Acid Degradation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001388.pub3]