N-Acetyl-L-histidine or N-Acetylhistidine, belongs to the class of organic compounds known as N-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom. N-Acetylhistidine can also be classified as an alpha amino acid or a derivatized alpha amino acid. Technically, N-Acetylhistidine is a biologically available N-terminal capped form of the proteinogenic alpha amino acid L-histidine. N-acetyl amino acids can be produced either via direct synthesis of specific N-acetyltransferases or via the proteolytic degradation of N-acetylated proteins by specific hydrolases. N-terminal acetylation of proteins is a widespread and highly conserved process in eukaryotes that is involved in protection and stability of proteins. Several proteins from prokaryotes and archaea are also modified by N-terminal acetylation. The majority of eukaryotic N-terminal-acetylation reactions occur through N-acetyltransferase enzymes or NAT. The substrate specificities of different NAT enzymes are mainly determined by the identities of the first two N-terminal residues of the target protein. The human NatA complex co-translationally acetylates N-termini that bear a small amino acid (A, S, T, C, and occasionally V and G). N-acetylated amino acids, such as N-acetylhistidine can be released by an N-acylpeptide hydrolase from peptides generated by proteolytic degradation. In addition to the NAT enzymes and protein-based acetylation, N-acetylation of free histidine can also occur. In particular, N-Acetylhistidine can be biosynthesized from L-histidine and acetyl-CoA by the enzyme histidine N-acetyltransferase (EC 2.3.1.33). Many N-acetylamino acids are classified as uremic toxins if present in high abundance in the serum or plasma. Uremic toxins are a diverse group of endogenously produced molecules that, if not properly cleared or eliminated by the kidneys, can cause kidney damage, cardiovascular disease and neurological deficits. In scientific studies, N-Acetyl-L-histidine has been examined for its potential neuroprotective effects in conditions such as age-related macular degeneration (AMD), retinitis pigmentosa, and glaucoma. It has also been investigated for its role in supporting retinal function and visual health. Additionally, it may modulate cellular signaling pathways involved in inflammation and cell survival.

Metabolism and Physiological Effects of N-Acetylhistidine References