Serine
Properties
| State | Solid (white crystalline powder) |
| Color | White |
| Solubility | Highly soluble in water (362 g/L at 25°C); insoluble in ethanol |
| Melting Point | 246°C (decomposes) |
| Boiling Point | Decomposes before boiling |
About Serine
Serine is a small polar amino acid with the formula C3H7NO3 and a molar mass of 105.093 g/mol. It's classified as non-essential because mammals synthesize it from glycine, threonine, or the glycolytic intermediate 3-phosphoglycerate via the phosphoserine pathway, but the metabolic load it carries is enormous out of proportion to its size. The hydroxyl side chain is the substrate for the largest single class of post-translational modifications in eukaryotes: serine phosphorylation by Ser/Thr kinases such as PKA, PKC, CDK, and the MAPK family generates an estimated 80 percent of the phosphoproteome and is the primary on/off switch for cell-cycle progression, metabolic enzyme activity, and signal transduction. The same hydroxyl serves as the nucleophile in the Ser-His-Asp catalytic triad of serine proteases — trypsin, chymotrypsin, elastase, thrombin, and the entire blood-coagulation cascade — where the activated serine alkoxide attacks the substrate carbonyl to form a transient acyl-enzyme intermediate. Serine is also the point of entry to one-carbon metabolism via serine hydroxymethyltransferase, which transfers serine's beta-carbon to tetrahydrofolate to make 5,10-methylene-THF, the carbon donor for thymidylate synthase and thus the dependency that 5-fluorouracil chemotherapy exploits. Serine was first isolated in 1865 from sericin, a silk protein, which gave it its name from Latin sericum.
Where you'll encounter it
If you've ever taken a phosphatase inhibitor cocktail (sodium fluoride, beta-glycerophosphate, sodium orthovanadate) when lysing cells for a Western blot, you were trying to preserve the phosphoserine and phosphothreonine signals that would otherwise be hydrolyzed in minutes by endogenous PP1 and PP2A phosphatases — that's how dynamic Ser phosphorylation actually is in a live cell. In an oncology research lab, the serine biosynthesis pathway has become a hot drug target: many cancers upregulate phosphoglycerate dehydrogenase (PHGDH) to feed both serine synthesis and one-carbon flux into nucleotide production, and PHGDH inhibitors like NCT-503 are in preclinical development. Outside the lab, you'll find serine in the natural moisturizing factor (NMF) of skin — about 12 percent of the free amino-acid pool in the stratum corneum is serine, which is why hydrolyzed silk-protein extracts show up on cosmetic ingredient lists targeted at dry-skin formulations.
Common Uses
- Substrate for Ser/Thr kinase phosphorylation studies in cell signaling research
- Nucleophile in the catalytic triad of trypsin, chymotrypsin, thrombin, and other serine proteases
- One-carbon donor via serine hydroxymethyltransferase to the folate cycle for nucleotide biosynthesis
- Component of natural moisturizing factor in stratum corneum skincare formulations
- Standard amino acid in defined cell-culture media (DMEM, RPMI) at 0.4 mM concentration
- Pharmaceutical excipient and parenteral nutrition amino-acid component
Safety Information
Generally Recognized As Safe (GRAS) by FDA for dietary use, with no upper intake limit established. GHS: not classified as hazardous. No OSHA PEL. Acute oral toxicity is essentially nil — rat LD50 exceeds 5 g/kg. Standard handling with nitrile gloves and dust mask if weighing large quantities is sufficient. The only practical caveat is that L-serine supplementation at gram-per-day doses is being studied for ALS and may interact with the methionine cycle, so research-grade L-serine should not be self-administered outside a clinical trial.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.