Biosynthesis of Salivary Mucins

Molnar et al. (1964) found that puromydn administered to intact rats almost completely inhibited incorporation of both glucosamine-l- C and DL-leucine-l- C into liver and plasma proteins. Inhibition of protein synthesis by puromycin indicates operation of the usual ribosomal mechanism of protein synthesis. Since the great bulk of carbohydrate incorporation into glycoprotein appears to occur by postribosomal mechanisms (see Section IV), inhibition of carbohydrate incorporation by puromycin suggests that there is no appreciable reservoir of nonglycosylated polypeptide in either rat liver or sheep submaxillary gland. 

The glutamine analog 6-diazo-5-oxo-L-norleucine (DON) inhibits L-glu-tamine n-fructose-6-phosphate amidotransferase (Section III) in the-pathway of conversion of C-glucose to both sialic acid and N-acetylga-lactosamine and, as expected, thereby inhibits incorporation of C-glu-cose into OSM. With glucose as the sole carbohydrate source in the incubation medium, DON also inhibits incorporation of radioactive amino acids into OSM but causes a concomitant increased incorporation of labeled amino acid into other protein fractions these latter proteins may contain nonglycosylated polypeptide precursors of OSM. All the inhibitory effects of DON are prevented if glucosamine is present in the incul ition medium. 

Prot -— GalNAc 1 CMP-sialic acid, Prot GalNAc -— SA  

Present knowledge on the biosynthesis of the prosthetic groups of OSM and porcine submaxillary mucin (PSM) is summarized in Fig. 12. Five glycosyltransferases are required for the synthesis of the most complex oligosaccharide side chain, the pentasaccharide present in PSM with human blood group A specificity (Carlson, 196, Section II). Four of these five enzymes are required for the synthesis of the side chain of blood group A-negative PSM two transferases are required for incorporation of the disaccharide side chain of OSM. 

Schachter and McGuire (1968) have stuAed in detail the properties of the galactosyltransferase which incorporates galactose from UDP-gal- 

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