L-(-)-SERINE

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L-(-)-serine's core role

• One-carbon unit donor: Provides a key carbon source (N5,N10-CH2-FH4) for purine and dTMP synthesis.
• Conditionally essential amino acid: Requires exogenous supplementation in cell culture to support proliferation.
• Neural function: Metabolized to produce D-serine, which regulates NMDA receptors and influences cognition.

Product information

Product packaging

• 25kg Drum of L-Serine
• Store away from light and moisture

Based on the mechanism of deoxysphingoid base generation, we hypothesized that

L-serine supplementation would be beneficial for both HSAN1 mice and humans. L-serine

is crucial for neuronal survival. Genetic disorders that reduce L-(-)-SERINE synthesis lead

to severe neurological phenotypes (18-20). Biochemical analyses indicate that L-serine is
synthesized from glucose and released by astrocytes, not neurons.

Peripheral nerves lack the abundant astrocytes found in the central nervous system,

which may explain why dorsal root ganglia are particularly vulnerable in HSAN1. Conversely,

we hypothesized that L-alanine would have detrimental effects on transgenic mice carrying

HSAN1 mutations in the SPTLC1 gene. By comparing these closely related yet distinct

effects in HSAN1 and their impact on the nervous system, we aim to elucidate the role of

sphingolipids in neuronal survival and health.

Results L-serine inhibits the production of doxSA in HEK293 cells Increasing the

concentration of L-alanine in the culture medium promotes the production of doxSA in

cultured cells with the wild-type SPTLC1, while increasing the concentration of L-serine

significantly inhibits the production of endogenous doxSA, even when the concentration
of alanine is elevated (Figure 2A).

This indicates a competitive inhibition between L-(-)-SERINE and L-alanine. In contrast,

the production of SA is significantly increased in the presence of L-serine, and it is not

significantly inhibited in the presence of L-alanine.

(A) Inhibition of doxSA production in SPTLC1 wild-type HEK cells by increasing the

concentration of L-serine in the culture medium against the background of different

L-alanine concentrations. (B) Inhibition of doxSA production in SPTLC1 wild-type and

HSAN1 mutant HEK293 cells with the increase of L-serine concentration in the culture
medium against the background of a constant 2 mM L-alanine.

Against the background of a constant 2 mM L-alanine, the production of doxSA in cells

expressing the HSAN1 mutation was significantly higher than that in wild-type cells

(Figure 2B). Similar to the cells expressing the wild-type SPTLC1, we observed that

with the increase of L-serine concentration in the culture medium, the production of

doxSA in cells expressing the HSAN1 mutation was also inhibited (Figure 2B), which

indicates that the production of harmful dSLs in HSAN1 can, in principle, be overcome

by increasing the systemic availability of L-(-)-SERINE.