Methionine and Cysteine - Nutrition

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What are Methionine and Cysteine?

Methionine and cysteine are sulphur containing amino acids. Cysteine is synthesized endogenously from methionine, and production of cysteine accounts for approximately half of the methionine requirement in the diet[1]. In this pathway methionine is converted to homocysteine, which in turn donates a sulphur group to serine (a non-essential amino acid) to ultimately form cysteine. Although methionine, but not cysteine, is considered an essential amino acid, the addition of dietary cysteine “spares” and reduces the metabolic requirement for methionine.

Methionine is a neutral amino acid, while cysteine is basic; both methionine and cysteine are gluconeogenic. Cysteine readily reacts with itself and other thiols (i.e. sulphur containing compounds) and cystine is formed from a disulphide bond between two cysteine molecules. Most of the plasma cysteine is actually found as cystine.

Dietary methionine is absorbed by a neutral amino acid transporter in the small intestine (particularly the jejunum) and plasma methionine is actively reabsorbed in the proximal tubule of the kidney; dietary cysteine and cystine are absorbed in the small intestine and actively reabsorbed in the proximal tubule of the kidney via a dibasic amino acid transporter.

Why are they Important?

Both methionine and cysteine are incorporated into structural protein and are required for normal growth. The sulphur side chains help stabilize secondary and tertiary protein structures. Methionine is part of the coenzyme S-adenosyl methionine, which influences and regulates the activity of a number of enzymatic and cellular replication processes.

Inherited defects in the transporter for dibasic amino acids can result in poor absorption of cyst(e)ine (as well as the other dibasic amino acids lysine, ornithine, and arginine) from the intestinal mucosa and poor reabsorption in the renal tubule[2]. Unlike lysine, ornithine and arginine, cystine is not soluble in urine and readily forms crystals and stones. Cystinuria and related dysuria and urinary obstructions due to cystine urolithiasis have been described in Newfoundlands, English bulldogs, and Dachshunds[3]. Increased intake of DL-methionine (either in the diet or as a supplement) has been used as a therapeutic treatment for sterile struvite crystalluria and urolithiasis[4][5]. The oxidation of dietary sulphur increases urinary excretion of ammonium (NH4+) resulting in a more acidic urinary pH.

Roles in the Body

Methionine is part of the coenzyme s-adenosylmethionine, which through its ability to transfer to and methylate other substrates, is able to modify the activities of a range of different metabolic processes including nucleic acids, proteins, lipds and secondary metabolites); it is also a constituent of protein, and a precursor of cysteine[6].

Cysteine readily forms sulphide bonds with other thiol groups stabilizing secondary and tertiary structure in proteins such as hair, glutathione, and insulin; and acts as a sulphur donor to choline, an essential vitamin-like nutrient[7]. Cysteine is a precursor to taurine in dogs, however cats have low activity of hepatic cysteine dioxygenase and cysteine sulphinate decarboxylase activity (two key enzymes in the conversion of cysteine to taurine) and require a preformed source of taurine in the diet[8]. Cysteine is also a precursor of felinine, a urine pheromone produced by cats that gives cat urine its distinctive aroma[9].

Consequences of Methionine and Cysteine Deficiency

Dogs:

Puppies fed a methionine deficient diet experience decreased food intake, weight loss and evidence of dermatitis[10]. In puppies, methionine deficiency in combination with excess cysteine resulted in hyperkaratotic, necrotic foot pad lesions[11], that resolved with reintroduction of methionine. Inadequate intake of sulphur amino acids without supplemental taurine has also been associated with development of taurine deficient cardiomyopathy[12][13], and pigmented gallstones[14] in adult dogs.

Cats:

Feeding of a methionine deficient diet to kittens resulted in weight loss, lethargy and abnormal ocular secretions[15][16]. Deficient methionine intake with adequate cysteine supplementation intake in kittens also resulted in severe perioral and foot pad lesions[7].

Toxicity

Dogs:

Cysteine excess with methionine deficiency in puppies resulted in foot pad lesions[11]. Excess methionine intake in adult dogs can result in ataxia, disorientation, lethargy, vomiting and ptylism[17].

Cats:

Kittens fed methionine in excess of 10 times the growth requirements experienced a decrease in weight gain though no other signs of toxicity[18]. Adult cats given excess methionine developed severe haemolytic anaemia with methaemoglobinemia and Heinz body formation[19].

Dietary Sources

Methionine and cysteine are found in highest concentrations in animal proteins (e.g. muscle, organ meats, and eggs), and are present but at much lower levels in dairy (e.g. casein), cereal grains, and pulses (i.e. legumes). Methionine and cysteine are often the most limiting amino acid in natural protein sources and are frequently supplemented into commercially-prepared dog and cat foods. Diets containing poorly digestible proteins may be inadequate to supply methionine and cysteine despite having adequate total crude protein levels[12].

Diagnosing Methionine and Cysteine Deficiency

Diagnosis of methionine and cysteine deficiency is based on fasted plasma amino acids.


References

  1. Teeter RG, et al. Methionine and cystine requirements of the cat. J Nutr 1978;108:291–295
  2. Hoppe A, et al. Urinary excretion of amino acids in normal and cystinuric dogs. Br Vet J 1993;149:253-68.
  3. Brons AK, et al. SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: A new classification system. JVIM 2013;27:1400-1408.
  4. Lemann J and Relman AS. The relation of sulfur metabolism to acid base balance and electrolyte excretion: the effects of DL-methionine in normal man. J Clin Invest 1959;38:2215-2223.
  5. Mishina M et al. Medical dissolution of struvite nephrolithiasis using amino acid preparations in dogs. JVIM 2000;62:889-892.
  6. Stipanuk MH and Watford M. Amino acid metabolism. In Biochemical and physiologic aspects of human nutrition. 2000 Philidelphia, PA: WB Saunders Company p. 265-270.
  7. 7.0 7.1 National Research Council (NRC). Protein and Amino Acids. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p. 125-126.
  8. De la Rosa J, et al. Metabolism of cysteine and cyteinesulfinate in rat and cat hepatocytes. J Nutr 1987;117:549-558.
  9. Hendriks WH, et al. Importance of sulfate, cysteine and methionine as precursors to felinine synthesis by domestic cats (Felis catus). Comp Biochem Physiol C Toxicol Pharmacol 2001;129:211–216.
  10. Milner JA. Assessment of indispensable and dispensable amino acids for the immature dog. J Nutr 1979;109:1161-1167.
  11. 11.0 11.1 Burns RA and Milner JA. Sulfur amino acid requirements of immature beagle dogs. J Nutr 1982;112:447-452.
  12. 12.0 12.1 Torres CL, et al. Taurine status in normal dogs fed a commercial diet associated with taurine deficiency and dilated cardiomyopathy. JAPAN(Berl) 2003;87:359-72.
  13. Backus RC, et al. Low Plasma Taurine Concentration in Newfoundland Dogs is Associated with Low Plasma Methionine and Cyst(e)ine Concentrations and Low Taurine Synthesis. J Nutr 2006;136:2525-2533.
  14. Christian JS and Rege RV. Methionine, but not taurine, protects against formation of canine pigmented gallstones. J Surg Res 1996;61:275-281.
  15. Teeter RG, et al. Essentiality of methionine in the cat. J Anim Sci 1978;46:1287-1292.
  16. Rogers QR and Morris JG. Essentiality of amino acids for the growing kitten. J Nutr 1979;109:718-723.
  17. Biourge VC, et al. Methionine toxicosis in a group of hunting dogs. Proc Am Acad Vet Nutr Res Symp Dallas, TX. 2002, p.9-10.
  18. Taylor TP, et al. Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near maximal growth in kittens. J Nutr 1996;126:2243-2252.
  19. Maede Y, et al. Methionine toxicosis in cats. AJVR 1987;48:289-292.



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