05. A and B transferases

 

Once the chemical structures defining the ABO blood system were determined, Watkins and Morgan, and separately Ceppellini, proposed a hypothesis on the biosynthetic pathway of these antigens. They postulated that A and B antigens are produced from the same precursor as an H antigen, which is abundant in individuals with blood group O. A and B antigens are formed by the action of glycosyltransferases encoded by functional alleles at the ABO genetic locus (The Central Dogma of ABO). Namely, the A allele encodes A transferase, which transfers a GalNAc to the H antigen. This synthesizes the A antigen. Similarly, the B allele encodes B transferase, which transfers a galactose molecule to the H antigen to synthesize the B antigen.

In addition to A and B transferases, there are other glycosyltransferases with α1-3 Gal(NAc) transferase activity/specificity. These include α1-3 Gal transferase to synthesize α1-3 Gal epitope (Gal α1-3 Gal β1-4 GlcNAc-), isogloboside 3 synthase to synthesize iGb3 ceramide (Gal α1-3 Gal β1-4 GlcCer-), and Forssman glycolipid synthase to synthesize the Forssman antigen (GalNAc α1-3 GalNAc β1-3 Gal α1-4 Gal β1-4 GlcCer-). Whether these glycosyltransferase genes are evolutionarily related to ABO genes was an important question.

06. A transferase cDNA cloning

01. ABO Blood Group System