Methionine and Cysteine - Nutrition
1. 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.
2. 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.5,6 The oxidation of dietary sulphur increases urinary excretion of ammonium (NH4+) resulting in a more acidic urinary pH.
3. 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 metabsolic processes including nucleic acids, proteins, lipds and secondary metabolites); it is also a constituent of protein, and a precursor of cysteine.4 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
4. 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 cardiomyopathy12,13 and pigmented gallstones14 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
5. 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 10x the growth requirements experienced a decreased in weight gain though no other signs of toxicity.18 Adult cats given excess methionine developed severe haemolytic anemia with methaemoglobinemia and Heinz body formation.19
6. 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
7. Diagnosing Methionine and Cysteine Deficiency
Diagnosis of methionine and cysteine deficiency is based on fasted plasma amino acids.