Reversible lysine acetylation regulates the activity of human glycine n-acyltransferase-like 2 (hGLYATL2) : Implications for production of glycine-conjugated signalling molecules

• Lysine acetylation is a major post-translational modification of proteins, and regulates many physiological processes such as metabolism, cell migration, ageing and inflammation. Proteomic studies have identified numerous lysine-acetylated proteins in human and mouse models (Kim et al, (2006) Mol. Cell. 23, 607-618). One family of proteins identified in this study was the murine glycine N-acyltransferase (GLYAT) enzymes, which are acetylated on lysine 19 (K19). Lysine 19 is a conserved residue in human glycine N-acyltransferase-like 2 (hGLYATL2) and in several other species, showing that this residue may be important for enzyme function. Mutation of lysine 19 (K19) in recombinant hGLYATL2 to glutamine (K19Q) and arginine (K19R) resulted in a 50-80% lower production of N-oleoyl glycine and N-arachidonoylglycine, indicating that lysine 19 is important for enzyme function. LC/MS/MS confirmed that K19 is not acetylated in wild-type hGLYATL2, indicating that K19 requires to be deacetylated for full activity. The hGLYATL2 enzyme conjugates medium- and long-chain saturated and unsaturated acyl-CoA esters to glycine, resulting in the production of N-oleoyl glycine and also N-arachidonoyl glycine. N-oleoyl glycine and N-arachidonoyl glycine are structurally and functionally related to endocannabinoids and have been identified as signalling molecules that regulate functions like the perception of pain, body temperature, and also have anti-inflammatory properties. In conclusion, acetylation of lysine(s) in hGLYATL2 regulate the enzyme activity, thus linking post-translational modification of proteins with the production of biological signalling molecules, the N-acyl glycines.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

Biochemistry

biokemi

Molecular Biology

molekylärbiologi

Cell Biology

cellbiologi

Publication and Content Type

ref (subject category)

art (subject category)