N-acetylglucosamine-6-phosphate deacetylase (AMDHD2)

N-acetylglucosamine-6-phosphate deacetylase (AMDHD2) is a dimeric enzyme of the amidohydrolase family that catalyzes the deacetylation of N-acetylglucosamine-6-phosphate (GlcNAc-6P) to glucosamine-6-phosphate within the hexosamine biosynthetic pathway (HBP)[1][3][5]. AMDHD2 acts as a negative regulator of cellular UDP-N-acetylglucosamine levels, balancing the activity of GFPT2 (glutamine fructose-6-phosphate amidotransferase 2) in cells where GFPT2 predominates over the common GFPT1 isoform[1][3]. Loss of AMDHD2 activity elevates UDP-GlcNAc and confers resistance to tunicamycin, a glycosylation inhibitor[1][3]. Mutations in AMDHD2 have been associated with altered metabolism and some congenital epilepsy disorders[5]. The crystal structure confirms a TIM-barrel fold and obligate dimerization, essential for function[1][3]. AMDHD2 is primarily localized in the nucleus[5]. It is considered a metabolic enzyme rather than a receptor or transporter, and is an emerging therapeutic target for modulating metabolic and glycosylation pathways.

Other names

Amidohydrolase domain containing 2AMDHD2CGI-14GlcNAc 6-P deacetylaseAmidohydrolase domain-containing protein 2Putative N-acetylglucosamine-6-phosphate deacetylase

Not established for any specific drug; theoretically, inhibition or modulation would alter UDP-GlcNAc levels in the hexosamine biosynthetic pathway, potentially affecting glycosylation and cellular metabolism[1][3][5].