In the LC-MS data we’ve gathered over the past year, there is frequently strong peaks for N-acetylated amino acids, and there is clear incorporation of labeled acetate from U-13C-glucose, showing that these species are endogenously synthesized (over 48h incubations, mostly). It’s intriguing because, as far as I can tell, there is no known mechanism for N-acetylation of free amino acids in humans.
What about protein acetylation? Free acetylated amino acids could be a product of breakdown of acetylated residues in protein, but the well known protein acetylations (lysine, for example) happens on amino acid side chains, not on the amine (alpha) nitrogen which is part of the peptide bond.
But it turns out that proteins are in fact often acetylated on their N- terminal amino acid. This phenomenon was discovered 40 years ago, but what the heck it’s good for is still being debated. So maybe this explains the N-acetyl amino acids we often see. Or maybe it’s something different entirely …
5 thoughts on “N-acetylated amino acids”
Since that is acetilated from glucose, it looks as it happens on purpose, not b y chance, right? So there have to be some enzymes for it. And there are too many of them to be just degradation product of N-acetilated proteins. Do they play some biological role by themself?
Certainly these are catalyzed reactions, and the enzymes (N-terminal acetyltransferases, NATs) have been identified; see the PLoS article linked to above. I don’t know if there is acetylation also of free amino acids, and if so what role that would serve.
Dear Prof Nilsson
Have you been able to identify enzymes that _N-acetylate free aminoacids since? I appreciate your feedback,
Prof RA Wevers, Emeritus Professor in Clinical Chemistry,
Translational Metabolic Laboratory – 830 TML
Department Laboratory Medicine, Radboud University Medical Centre
Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands
Hi Ron, no unfortunately we haven’t had the time to do follow-up work on the N-acetylated amino acids. We see them all the time in both cell extracts and plasma, but it’s still unclear to me if they are formed as free metabolites or if they are remnants of protein N-acetylation.
I am VP at Human Metabolome Technologies providing metabolomics analysis for global clients. I have asked myself this question as well. Acetyl-CoA is a source of acetyl often linked to histone acetylation. Your observation of C13-glucose directly links glycolysis to Acetyl-CoA to N-terminal amino acid acetylation. Which amino acids and how they correlate to disease or amino acid metabolism is unclear, or how may be related to microbiome also unclear. These seems to be selectivity to which amino acids. Not all are essential or non-essential. Is this linked to nutrient availability? Amino acid sensing – transport? Flux rate of consumption (not related to protein synthesis but amino acid transformation during high glycolytic demand or proliferation as in stem cells differentiation, cancer?