Understanding L-Amino Acids vs D-Amino Acids: Essential Building Blocks of Life
Amino acids are the fundamental components of proteins. Except for glycine, each exists as two non-superimposable mirror images (enantiomers): an L- form and a D- form. These mirror images can behave very differently in biology.
The molecular mirror: what L and D actually mean
L/D notation does not equal “levo/dextro” optical rotation. L and D are assigned by comparing a molecule’s configuration (in a Fischer projection) to that of reference D-/L-glyceraldehyde. Some L-amino acids rotate plane-polarized light to the right (+), and some D-amino acids rotate it to the left (−)—so L/D ≠ levo/dextro. Clear primers: ChemLibreTexts.
L-amino acids: life’s default for ribosomal proteins
Across animals, plants, fungi, and most bacteria, ribosomes incorporate L-amino acids into proteins. This biological “handedness” (homochirality) is a universal hallmark of life and a longstanding origin-of-life question. For reviews on homochirality mechanisms and prebiotic enantioenrichment, see Blackmond (Cold Spring Harbor Perspectives in Biology): 2019 review and an earlier overview via PMC.
D-amino acids: not just curiosities
Bacteria: cell walls and signaling
Many bacteria use D-alanine and D-glutamate in peptidoglycan cell walls, and diverse D-amino acids regulate growth and remodeling. See Cava et al., FEMS Microbiol Rev: PubMed abstract and full text on PMC; for visualization of D-amino acids in peptidoglycan, see an ACS Chem Biol study here.
Mammals: D-serine in the brain
D-serine functions as an endogenous co-agonist at the NMDA-type glutamate receptor’s glycine site, shaping synaptic plasticity. Landmark paper: Mothet et al., PNAS 2000 (PDF | PubMed). Reviews: Wolosker, FEBS J 2008 (link); Snyder, Trends Pharmacol Sci 2000 (PubMed).
Similarities and differences
- Shared backbone: α-carbon bearing an amino group, carboxyl group, hydrogen, and an R-side chain.
- Key difference: spatial arrangement around the α-carbon (chirality) determines fit in enzymes, transporters, and receptors—hence different biological roles.
Why this matters for biochemistry, nutrition, and therapeutics
Understanding L/D stereochemistry informs protein synthesis, peptide drug design (D-residues can boost stability), microbiome interactions (bacterial D-amino acids), and neurobiology (D-serine). It also anchors the broader question of why biology chose one handedness—homochirality—at origin.
• L/D does not tell you optical rotation (+/−).
• D-amino acids are not “absent” from humans: D-serine (and D-aspartate) occur in the brain and endocrine tissues.
• Glycine is achiral—no L or D form.
Next step: getting the right aminos in practice
For nutrition, you want complete coverage of the nine essential L-amino acids (the form your ribosomes use), especially around training or when appetite is limited.
Learn about FUNDAMINOS® (complete essential amino acids)
Selected references
- Blackmond DG. The Origin of Biological Homochirality. Cold Spring Harb Perspect Biol, 2019. PDF | PMC overview
- Cava F. et al. Emerging knowledge of regulatory roles of D-amino acids in bacteria. FEMS Microbiol Rev, 2011. PubMed | PMC
- Mothet JP. et al. D-serine is an endogenous ligand for the NMDA receptor glycine site. PNAS, 2000. PDF
- Wolosker H. D-serine in neurotransmission and neurodegeneration. FEBS J, 2008. Link
- Cepko CL et al. (ACS Chem Biol). D-amino acid chemical reporters reveal peptidoglycan dynamics. Link
- Orientation primer (L/D vs +/−): ChemLibreTexts