Neuraminic acid enzymic modification

Introduction of a fluoride at the 3-position of neuraminic acid yielded a compound (57) that was a competitive inhibitor of the a-(2,6)-sialyl-trans-ferase. Base and sugar-modified analogues of CMP-Neu5Ac have also been prepared to investigate the tolerance of oc-(2,6)-sialyl-transferase to base exchange (58) and modification of the 5-, 8- or 9-position of neuraminic acid (59), (60). While base-exchange was not tolerated, modifications of the acid moiety yielded compounds that were substrates for the enzyme. 

The effect of cortisone and. thyroxine on j8-D-glucuronidase levels in rat forebrain and cerebellum have been examined during early postnatal development. To investigate the chemical relationships between rat liver lysosomal and microsomal j3-D-glucuronidase, which are essentially identical catalytically and in reactivity with antibody and are similar in molecular weight, the two enzymes were isolated by procedures in which modifications of the proteins were avoided. The enzymes were found to differ in both carbohydrate and amino-acid compositions. The microsomal enzyme contained much more D-mannose and, in contrast to the lysosomal enzyme, contained neuraminic acid but no D-glucose. 

After the formation of NeuSAc a variety of reactions occur leading to modified and activated sialic acids. The oecurrence of the different sialic acids is documented in chapter B. The principal modifications are enzymic conversion of the N-acetyl group to an N-glycolyl moiety and the 0-acylation at positions 4, 7, 8, and 9 of the neuraminic acid molecule (Schauer 1978). 

The 5-N-acetyl group of CMP-A -acetylneuraminic acid can be modified by a hydroxylase to form CMP-7V-glycolyl-neuraminic acid. The enzyme occurs in many non-human tissues and has been cloned from several species [113]. JV-Glycolyl-neuraminic acid can then be transferred by sialyltransferases to glycoproteins and mucins, resulting in a sialic acid modification which is common in manunalians but in humans is antigenic, and only found in exceptional conditions such as in cancer (5). 

---