L-serine

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

L-Serine may be derived from dietary intake, endogenous biosynthesis from the glycolytic intermediate 3-phosphoglycerate, from glycine, or/and by protein and phospholipid degradation. L-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. As with most nutrients, plasma amino acid concentration is subject to homeostasis.

 

Adsorption

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.

 

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.

Serine is highly concentrated in all cell membranes. Low-average concentration of serine compared to other amino acids is found in muscle.

Plasma L-serine concentrations in normal subjects are reported to be above 100 µM (e.g. 114 +/- 33 with plasma samples collected from healthy volunteers after an overnight fast; Cynober 2002).

 

Metabolism

Because L-serine and glycine are readily interconverted, the pathways for glycine metabolism apply to L-serine as well.

In humans L-serine is utilized in several ways. In the “non-phosphorylated” pathway serine:pyruvate/alanine:glyoxylate aminotransferase converts L-serine to hydroxypyruvate. The formation of hydroxypyruvate is also the first step of the biosynthetic pathway of glyoxylate formation. L-Serine is also used for the formation of D-serine and pyruvate via the D/L-serine racemase. Another pathway of L-serine catabolism is initiated by serine hydroxymethyltransferase finally providing formyl groups for purine synthesis and methyl groups for pyrimidene synthesis. As a result also glycine is built. Also phosphoglycerols and cytidine diphosphodiacylglycerol are formed from L-serine. Finally sphingosine is synthesized from L-serine and palmityl-CoA. (for detailed review see Koning et al 2003).

 

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-serine is used by the organism after oral uptake. L-Serine is rapidly converted and metabolised. An increase in blood levels of L-serine after oral uptake occurs only at high dose levels. For risk assessment purposes oral absorption of L-serine is set at 100%.

 

The substance is of low volatility due to a low vapour pressure (< 0.00147 Pa). Due to the large particle size of the substance and a low volatility it is not to be expected that L-serine 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-serine reaching the lungs might be absorbed through aqueous pores. (ECHA, 2008) For risk assessment purposes, although it is unlikely that L-serine 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-serine is set at 100%.

L-Serine 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-serine is proposed for risk assessment purposes.