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| Targets |
L-Serine-13C has no independent pharmacological target as a stable isotope tracer. The unlabeled L-serine is a non-essential amino acid that plays a central role in cellular proliferation and growth. It is produced from 3-phosphoglycerate in a multistep biosynthesis catalyzed by phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). L-Serine is the precursor for glycine, cysteine, and phospholipids. Defective L-serine biosynthesis is associated with neural tube defects and deoxysphingolipid accumulation in Neu-Laxova syndrome (PGDH mutation). Dysregulation of L-serine phosphorylation is associated with Alzheimer's disease and ALS.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
As a stable isotope tracer/internal standard, L-Serine-13C is not tested for in vitro pharmacological activity. It is used in cell culture studies as an internal standard for LC-MS quantification of L-serine, or as a metabolic tracer to study one-carbon metabolism, serine biosynthesis, and serine conversion to glycine via serine hydroxymethyltransferase (SHMT). The 13C label enables precise tracking of carbon atoms through nucleotide and phospholipid biosynthesis pathways without interfering with normal cellular processes. |
| ln Vivo |
L-Serine-13C has no independent in vivo pharmacological activity as a therapeutic agent. It is used in animal and human studies as a stable isotope tracer administered orally or intravenously to study serine metabolism, one-carbon metabolism, and glycine synthesis. L-Serine-13C can be used to trace the flux of serine through the folate cycle and methionine cycle, and to quantify the contribution of de novo serine synthesis vs. dietary serine in various tissues. L-Serine itself is being investigated for therapeutic potential in neurological disorders.
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| Enzyme Assay |
For in vitro LC-MS/MS quantification, L-Serine-13C is dissolved in an appropriate solvent (water, 0.1% formic acid, or methanol) to prepare a stock solution (e.g., 1 mg/mL). The internal standard is added to biological samples (plasma, serum, cell lysates, culture media, cerebrospinal fluid) at a fixed concentration (e.g., 10-500 ng/mL). Protein precipitation is performed by adding 3-5 volumes of methanol or acetonitrile containing the internal standard, followed by vortexing and centrifugation (10,000-15,000 rpm, 10 minutes). The supernatant is transferred and analyzed by LC-MS/MS. For derivatization-based GC-MS methods, samples are derivatized with MTBSTFA or other agents. The serine/serine-13C peak area ratio is used for quantification. For tracer experiments, L-Serine-13C is added to cell culture media at 10-500 uM for metabolic labeling studies.
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| Cell Assay |
For cell-based tracer studies, cells (e.g., cancer cells with activated serine synthesis, hepatocytes, neurons) are cultured in standard medium (DMEM with 10% FBS, 2 mM glutamine). The medium is then replaced with serine-free defined medium containing L-Serine-13C at a defined concentration (10-500 uM). Cells are incubated for 1-48 hours at 37degC in 5% CO2. At each time point, cells are washed with PBS and lysed in 0.1% formic acid in methanol. After protein precipitation and centrifugation, the supernatant is analyzed by LC-MS/MS to quantify 13C-labeled serine and its downstream metabolites (glycine, cysteine, glutathione, formate, 5,10-methylenetetrahydrofolate, and nucleotide precursors). For flux analysis, the rate of 13C incorporation into serine, glycine, and nucleotides is calculated. For SHMT activity assays, the rate of conversion of L-Serine-13C to glycine-13C is measured.
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| Animal Protocol |
For in vivo tracer studies, L-Serine-13C is administered to rodents via intravenous injection, intraperitoneal injection (50-200 mg/kg), or oral gavage (100-500 mg/kg). Blood samples are collected at multiple time points (0, 15, 30, 60, 120, 240 minutes). For brain studies, animals are euthanized and brain regions (cortex, hippocampus, cerebellum) are dissected. At terminal time points, tissues (liver, kidney, pancreas, small intestine) are harvested, snap-frozen in liquid nitrogen, and stored at -80degC. Tissues are homogenized in 0.1% formic acid in methanol, centrifuged, and analyzed by LC-MS/MS to quantify 13C-labeled serine, glycine, and folate cycle intermediates. For 13C-NMR-based flux analysis, tissue extracts are analyzed by 13C-NMR to determine labeling patterns in serine, glycine, and other metabolites. For breath analysis, 13CO2 can be collected from expired air.
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| ADME/Pharmacokinetics |
L-Serine-13C is a stable isotope tracer and does not have independent pharmacokinetic parameters. L-Serine is an endogenous non-essential amino acid with a plasma half-life of approximately 30-90 minutes in humans. It is absorbed from the small intestine, distributed to all tissues, and crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1). Normal plasma serine levels are 50-150 uM. L-Serine is metabolized via serine hydroxymethyltransferase (SHMT) to glycine, donating a one-carbon unit to the folate cycle. Serine is also a precursor for phosphatidylserine and sphingolipids. The kidney and liver are major sites of serine synthesis (via the phosphorylated pathway). The 13C label enables precise tracking of these processes without altering pharmacokinetics.
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| Toxicity/Toxicokinetics |
L-Serine is a naturally occurring non-essential amino acid with low toxicity. The LD50 in rodents is >5,000 mg/kg. The 13C-labeled version is chemically identical except for isotopic substitution and exhibits the same safety profile. High-dose L-serine supplementation (0.5-2 g/kg/day in animal studies) is generally well-tolerated. Neu-Laxova syndrome is associated with defective serine biosynthesis due to PGDH mutations, and L-serine supplementation is being investigated as a potential treatment. Standard laboratory safety precautions for handling amino acids apply. Not intended for human consumption.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
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| Additional Infomation |
L-Serine-13C is not a drug but a 13C-labeled stable isotope tracer and internal standard. It has no approved therapeutic status, no clinical trial history as a separate agent, and is not intended for human consumption. This compound is used for research applications including as an internal standard for GC-MS or LC-MS quantification of L-serine in biological samples, metabolic tracer studies of one-carbon metabolism and the folate cycle, studies of serine biosynthesis via the phosphorylated pathway (PGDH, PSAT, PSP), research on de novo serine synthesis in cancer cells (Warburg effect, serine addiction), investigations of serine/glycine metabolism in neurological disorders (Alzheimer's disease, amyotrophic lateral sclerosis, Neu-Laxova syndrome), and flux analysis of serine conversion to glycine via SHMT. The compound is also used as an internal standard for D-serine and L-serine quantification in biological fluids. Available with high isotopic enrichment (≥99 atom% 13C).
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| Molecular Formula |
C213CH7NO3
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| Molecular Weight |
106.09
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| Exact Mass |
105.043
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| CAS # |
89232-77-9
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| Related CAS # |
L-Serine;56-45-1
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| PubChem CID |
10796713
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| Appearance |
White to off-white solid powder
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| LogP |
-3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
7
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| Complexity |
72.6
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O[13CH2][C@@H](C(=O)O)N
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| InChi Key |
MTCFGRXMJLQNBG-IJGDANSWSA-N
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| InChi Code |
InChI=1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1/i1+1
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| Chemical Name |
(2S)-2-amino-3-hydroxy(313C)propanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 9.4260 mL | 47.1298 mL | 94.2596 mL | |
| 5 mM | 1.8852 mL | 9.4260 mL | 18.8519 mL | |
| 10 mM | 0.9426 mL | 4.7130 mL | 9.4260 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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