Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase (CMAH)

  • Anne K. Bergfeld
  • Ajit Varki
Reference work entry


Sialic acids are a family of more than 50 naturally occurring acidic nine-carbon backbone monosaccharides. The predominant sialic acids in mammals are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), which commonly occupy the terminal positions of various glycan chains (Varki and Schauer 2009). The only known biosynthetic pathway for generation of Neu5Gc takes place in the cytosol and is catalyzed by the cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah). The Cmah enzyme acts only at the level of activated sugars and catalyzes the conversion of the precursor molecule CMP-Neu5Ac to CMP-Neu5Gc involving a complex mechanism with cofactors NADH, cytochrome b5, b5 reductase, iron, and molecular oxygen (Shaw and Schauer 1988; Muchmore et al. 1989; Kozutsumi et al. 1990; Shaw et al. 1992, 1994; Kawano et al. 1993, 1995; Schneckenburger et al. 1994; Takematsu et al. 1994; Schlenzka et al. 1996). The Cmah enzyme is conserved among animals of the deuterostome lineage (vertebrates and “higher” invertebrates), but no homologous enzymes are known in any other eukaryotic taxa (Varki 2009). Only distantly related bacterial and plant hydroxylases were predicted to have some degree of structural similarity to Cmah (Schmidt and Shaw 2001). Interestingly, N-glycolyl groups are very rare in nature. Besides the Cmah enzyme, only one bacterial enzyme is known to be capable of generating N-glycolyl groups in the form of N-glycolylmuramic acid in mycobacteria (Raymond et al. 2005). Notably, the responsible gene namH shows distant homology to CMAH and acts on a nucleotide sugar (UDP-N-acetylmuramic acid) as well.


Sialic Acid Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Polysialic Acid Acid Hydroxylase 
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Supported by NIH grant R01GM32373.


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© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Cellular and Molecular MedicineUniversity of California, San DiegoLa JollaUSA

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