Amino Acid Degradation


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.


Amelio I, Cutrozzolá F, Antonov A, et al. (2014) Serine and glycine metabolism in cancer. Trends in Biochemical Sciences 39: 191–198.

Andreesen JR (2004) Glycine reductase mechanism. Current Opinion in Chemical Biology 8: 454–461.

Aquaron R (2013) Alkaptonuria: a very rare metabolic disease. Indian Journal of Biochemistry and Biophysics 50: 339–344.

Avila A, Nguyen L and Rigo JM (2013) Glycine receptors and brain development. Frontiers in Cellular Neuroscience 7: 1–11.

Awasthy D, Bharath B, Subbulakshmi V, et al. (2012) Alanine racemase mutants of Mycobacterium tuberculosis require D‐alanine for growth and are defective for survival in macrophages and mice. Microbiology 158: 319–327.

Bao A, Zhao Z, Din G, et al. (2014) Accumulated expression level of cytosolic glutamine synthetase 1 gene (OsGS1;1 or OsGS1;2) alter plant development and the carbon‐nitrogen metabolic status in rice. PLoS One 9: e95581.

Bisht S, Rajaram V, Bharath SR, et al. (2012) Crystal structure of Escherichia coli diaminopropionate ammonia‐lyase reveals mechanism of enzyme activation and catalysis. Journal of Biological Chemistry 287: 20369–20381.

Burman J, Harris RL, Hauton KA, et al. (2004) The iron‐sulfur cluster in the L‐serine dehydratase TdcG from Escherichia coli is required for enzyme activity. FEBS Letters 576: 442–444.

Chen S, Xu XL and Grant GA (2012) Allosteric activation and contrasting properties of L‐serine dehydratase types 1 and 2. Biochemistry 51: 5320–5328.

Chou HT, Kwon DH, Hegazy M, et al. (2008) Transcriptime analysis of agmatine and putrescine catabolism in Pseudomonas aeruginosa PAO1. Journal of Bacteriology 190: 1966–1975.

Chuang DT, Chuang JL and Wynn RM (2006) Lessons from genetic disorders of branched‐chain amino acid metabolism. Journal of Nutrition 136: 243S–249S.

Commichau FM, Gunka K, Landmann JJ, et al. (2008) Glutamate metabolism in Bacillus subtilis: gene expression and enzyme activities evolved to avoid futile cycles and to allow rapid responses to perturbations in the system. Journal of Bacteriology 190: 3557–3564.

De Koning TJ, Snell K, Duran M, et al. (2003) L‐serine in disease and development. Biochemical Journal 371: 653–661.

Deodato F, Boenzi S, Santorelli FM, et al. (2006) Methylmalonic and propionic aciduria. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 142C: 104–112.

Eylert E, Schär J, Merins S, et al. (2008) Carbon metabolism of Listeria monocytogenes growing inside macrophages. Molecular Microbiology 69: 1008–1017.

Fait A, Nesi AN, Angelovici R, et al. (2011) Targeted enhancement of glutamate‐to‐γ‐aminobutyrate conversion in Arabidopsis seeds affects carbon‐nitrogen balance and storage reserves in a development‐dependent manner. Plant Physiology 157: 1026–1042.

Florio R, di Salvo ML, Vivoli M, et al. (2011) Serine hydroxymethyltransferase: a model enzyme for mechanistic, structural, and evolutionary studies. Biochimica et Biophysica Acta 1814: 1489–1496.

Grabowski R, Hofmeister AEM and Buckel W (1993) Bacterial l‐serine dehydratases: a new family of enzymes containing iron–sulfur clusters. Trends in Biochemical Sciences 18: 297–300.

Ip YK and Chew SF (2010) Ammonia production, excretion, toxicity, and defense in fish: a review. Frontiers in Physiology 4 article 134: 1–20.

Kikuchi G, Motokawa Y, Yoshida T, et al. (2008) Glycine cleavage system: reaction mechanism, physiological significance and hyperglycinemia. Proceedings of the Japan Academy, Series B. Physical and Biological Sciences 84: 246–263.

Krzycki JA (2013) The path of lysine to pyrrolysine. Current Opinion in Chemical Biology 17: 619–625.

Márquez J, de la Oliva AR, Matés JM, et al. (2006) Glutaminase: a multifaceted protein not only involved in generating glutamate. Neurochemistry International 48: 465–471.

Matés JM, Segura JA, Martin‐Rufián M, et al. (2013) Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer. Current Molecular Medicine 13: 514–534.

McPhalen CA, Vincent MG, Picot D, et al. (1992) Domain closure in mitochondrial aspartate aminotransferases. Journal of Molecular Biology 227: 197–213.

Melo DR, Kowaltowski AJ, Wajner M, et al. (2011) Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic aciduria. Journal of Bioenergetics and Biomembranes 43: 39–46.

Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine metabolism. Annual Review of Nutrition 22: 87–105.

Nagamani SC, Erez A and Lee B (2012) Arginosccinate lyase deficiency. Genetics in Medicine 14: 501–507.

Ohtsu H (2010) Histamine synthesis and lessons learned from histidine decarboxylase deficient mice. Advances in Experimental Medicine and Biology 709: 21–31.

Rajagopalan KN and DeBernardinis RJ (2011) Role of glutamine in cancer: therapeutic and imaging implications. Journal of Nuclear Medicine 52: 1005–1008.

Roche B, Aussel L, Ezraty B, et al. (2013) Iron/sulphur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochimica et Biophysica Acta 1827: 455–469.

Scriver CR (2001) Garrod's foresight; our hindsight. Journal of Inherited Metabolic Diseases 24: 93–116.

Shanware NP, Mullen AR, DeBernardinis RJ, et al. (2011) Glutamine: pleiotropic roles in tumour growth and stress resistance. Journal of Molecular Medicine 89: 229–236.

Uvardi M and Poole PS (2013) Transport and metabolism in legume‐rhizobia symbioses. Annual Reviews in Plant Biology 64: 781–805.

White JP, Prell J, Ramachandran VK, et al. (2009) Characterization of a (gamma)‐aminobutyric acid transport system of Rhizobium leguminosarum bv. viciae 3841. Journal of Bacteriology 191: 1547–1555.

Wu G (2009) Amino acids: metabolism, functions and nutrition. Amino Acids (Epub. 1438–2199).

Further Reading

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

Lengler JW, Drews G and Schlegel HG (eds) (1998) Biology of the Prokaryotes. Oxford, UK: Blackwell Science.

Meister A (1965) Biochemistry of the Amino Acids. London, UK: Academic Press.

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. [doi: 10.1002/9780470015902.a0001388.pub3]