Biosynthesis of Amino Sugars

Glycoproteins contain amino sugars, which are synthesized for

F-6-P + Gln ----> glucosamine-6-phosphate + Glu

Have an internal redox C-1 oxidized, C-2 reduced

Summary of the synthesis of other amino sugars:

GlcNAc ----> GalNAc ----> ManNAc ----> NeuNAc (Sialic acid)

glucosamine-6-phosphate + Ac-CoA ----> NAc-glucosamine-6-phosphate

mutase

NAc-glucosamine-6-phosphate ----> NAc-glucosamine-1-phosphate

NAc-glucosamine-1-phosphate + UTP ----> UDP-NAc-glucosamine + PPi

UDP-NAc-glucosamine ----> UDP-NAc-galactosamine

UDP-NAc-glucosamine ----> NAc-mannosamine + UDP

NAc-mannosamine + PEP ----> NAc-neuraminic acid (sometimes called sialic acid)

It is incorporated as CMP-sialic acid

Milk Sugar (Lactose):

galactosyl transferase

UDP-Gal + GlcNAc ----> UDP + NAc-lactosamine

When females give birth, they produce a hormone that stimulates the synthesis of a-lactalbumin:

galactosyl transferase- a-lactalbumin

UDP-Gal + Glc ----> UDP + lactose

The association of the lactalbumin with galactosyl transferase changes the enzyme's substrate specificity!!

O-linked Glycoproteins

a. attached at the amino acids Ser or Thr

b. no carrier is required. Enzymes add sugars, as nucleotides, directly (UDP-GlcNAc, UDP-GalNAc, CMP-Sialic acid, GDP-Fuc [fucose = 6 deoxy-L-galactose])

c. involves a sequence of specific enzymes each will only add a certain sugar to a specific existing carbohydrate structure

N-linked Glycoproteins

Draw a structure of SER, RER, and Golgi apparatus on board --

a. attached the carbohydrate to the amino acid Asn (Asn-X-Ser/Thr)

b. use dolichol phosphate as carrier

c. sequence of enzymes make dolichol-P-CHO precursor in smooth endoplasmic reticulum (SER)

d. sequence of enzymes tranfer and modify (by hydrolysis) CHO precursor in rough endoplasmic reticulum (RER)

e. more modification (addition and removal) is facilitated by additional enzymes in the Golgi apparatus

SER = adds GlcNAc(2), Man (9), Glc (3)

RER = transfers CHO from dolichol; removes Glc(3), Man (1)

Golgi = removes Man (5), adds Glc (2), Gal (2 on and off), Glc (2), Sia (2), Fuc (1)

Final products can be classified into three groups:

a. high mannose (8-9)

b. complex (Golgi)

c. hybrid - more mannose than others (above core)

Targeting: The presence of mannose-6-phosphate targets a glycoprotein to the lysozome.