L-methionine

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

As an essential amino acid, L-methionine is not synthesized de novo in humans, and must therefore be ingested (methionine or methionine-containing proteins). Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Its derivative S-adenosyl methionine (SAM) serves as a methyl donor. As with most nutrients, plasma amino acid concentration is subject to homeostasis.

 

Absorption

Ingested dietary protein is denatured in the stomach due to low pH. Denaturing and unfolding of the protein makes the chain susceptible to proteolysis. Up to 15% of dietary protein may be cleaved to peptides and amino acids by pepsins in the stomach. In the duodenum and small intestine digestion continues through hydrolytic enzymes (e.g. trypsin, chymotrypsins, elastase, carboxypeptidase). The resultant mixture of peptides and amino acids is then transported into the mucosal cells by specific carrier systems for amino acids and for di- and tripeptides. L-Methionine (L-Met) is absorbed by sodium-dependent (e.g. neutral brush border (NBB) or Phe transporter) and sodium-independent transport systems in the brush border membrane. 

 

Distribution

Absorbed peptides are further hydrolysed resulting in free amino acids which are secreted into the portal blood by specific carrier systems in the mucosal cell. Alternatively they are metabolised within the cell itself. Absorbed amino acids pass into the liver where a portion of the amino acids are used. The remainder pass through into the systemic circulation and are utilised by the peripheral tissue. Plasma L-methionine concentrations in normal subjects are reported to be between 20 and 30 µM (25 +/- 4 µM with plasma samples collected from healthy volunteers after an overnight fast; Cynober 2002). The pancreas, liver, bladder, and kidney showed the greatest initial uptake. The pancreas and liver had the highest retention of activity among the organs studied (Deloar et al. 1998).

 

Metabolism

Methionine is mainly used for protein synthesis or is alternatively metabolised to homocysteine via S-adenosyl-methionine and S-adenosyl-homocysteine or transaminated to 3-methylthiopropionate and then to volatile sulphur compounds (methanethiol and/or hydrogen sulphide). Homocysteine can further be converted to cystathione and then to cysteine or it may be recycled to methionine using 5-methyltetrahydrofolate or betaine (from diet or choline oxidation) as the methyl donor.

Transmethylation and transsulphuration are the major pathways for the catabolism of methionine, whereas the transamination processes appear to become more significant at excessive methionine intakes leading to methionine toxicity (e.g. Brosnan and Brosnan 2006).

 

Excretion

Body losses of amino acids are minimal because amino acids filtered by the kidneys are actively reabsorbed. Also cutaneous losses are negligible. Since there is no long term storage for amino acids in mammals, excess amino acids are degraded, mainly in the liver. Metabolism of amino acids involves removal of the amino group which is converted to urea and excreted in the urine. After removal of the amino group the rest of the acid is utilised as energy source or in anabolism of other endogenous substances.

 

It is assumed that 100% L-methionine is used by the organism after oral uptake.

The substance is of low volatility due to a low vapour pressure. Due to the large particle size of the substance and a low volatility it is not to be expected that L-methionine reaches the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region in significant amounts. However, being a very hydrophilic substance with a molecular weight below 200, any L-methionine reaching the lungs might be absorbed through aqueous pores. (ECHA, 2008) For risk assessment purposes, although it is unlikely that L-methionine will be available to a high extent after inhalation via the lungs due to the low vapour pressure and high mass median diameter, the inhalation absorption of L-methionine is set at 100%.

L-Methionine with high water solubility and the log P value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of L-methionine is proposed for risk assessment purposes.

References:

Brosnan J.T. and Brosnan M.E. (2006). The sulfur-containing amino acids: an overview.

Cynober L.A. (2002). Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance.Nutrition.2002 Sep;18(9):761-6.

Deloar HM,Fujiwara T,Nakamura T,Itoh M,Imai D,Miyake M,Watanuki S. (1998). Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body positron emission tomography.Eur J Nucl Med.1998 Jun;25(6):629-33.