320

chapter 16

Carbohydrate Metabolism III: Glycoproteins, Glycolipids, GPI Anchors, Proteoglycans, and Peptidoglycans

in the biochemistry of GPI anchors may lead to novel

therapeutic agents to fight infections and possibly other

diseases.

Biosynthesis of Glycosphingolipids

The glycosphingolipids (GSLs, glycolipids) include neu-

tral glycosphingolipids, gangliosides,

and sulfatogly-

cosphingolipids. The terms “cerebroside” and “ganglio-

side” reflect their abundance in gray and white matter of

the central nervous system. Glycolipids are widely dis-

tributed in the body. Gangliosides

Gmi

and GTib have

been found to enhance the effect of nerve growth fac-

tor (NGF) on neurite outgrowth. Such studies may lead

to effective treatments after spinal cord injury. Ganglio-

sides also are known to modulate protein kinase and

NGF receptor function. All glycosphingolipids contain an

oligosaccharide chain of one or more residues of galactose,

glucose, N-acetylglucosamine, N-acetylgalactosamine, or

fucose. Gangliosides also have one or more residues of

sialic acid, whereas the sulfatoglycosphingolipids con-

tain sulfate groups in ester linkage on some residues.

Structures of the glycosphingolipids are presented in

Chapter 10.

GSLs are classified by the sequence and type of the

first four sugars attached to ceramide (Table 16-1). The

prefixes used to indicate the core structure are listed in

Table 16-1, along with the tissue in which the different

types are predominantly found. This system reflects the

synthetic history of a structure and is useful for under-

standing biosynthetic pathways. Structures of the three

most abundant glycolipids and the tissues in which they

occur are shown in Table 16-1.

GSLs of the ganglio- series are designated by the

capital letter G and the sialic acid content is desig-

nated by a subscripted capital letter (A = asialo; M =

monosialo; D = disialo; etc.). The length of the neu-

tral sugar chain is designated by a subscripted number

using the formula (5 —

n)

where

n

equals the number

of neutral sugars in the ganglioside. Further designa-

tions of

a

or /3 relate to the positioning of the sialic

acid. Using this nomenclature, Gmi is a ganglioside con-

taining one sialic acid and four neutral sugars (Figure

16-14). The initial glucosylation of ceramide occurs on

the cytoplasmic side of the Golgi while subsequent step-

wise sugar transfers occur within the Golgi lumen and

may result in 300-400 possible GSL types in differ-

ent cells. Subcellular fractionation and drug studies that

disrupt Golgi function have suggested that the distribu-

tion of glycosyltransferases synthesizing GSLs may differ

from enzymes involved in N-linked glycoprotein synthesis

(Figure 16-15).

During the progression of cancer, many changes in gly-

cosyltransferases result in alteration of oligosaccharides

TABLE 16-1

N a m es, S tru ctu res, a n d M a jo r T issue D istrib u tio n s o f O lig o sa cch a rid es F o u n d in G lyco lip id s

Name/Prefix*

Structure*

Distribution*

Lacto

Gal/31 —>3GlcNAcß 1

->3Ga\ß

1

->4G\cß\

-ACer

Central nervous system

Lactoneo

Gal/31 ->4GlcNAc /31 ^3Gal/31 -^4Glc/31 -ACer

Central nervous system, blood

group antigens

Muco

Gal/31 —>3Gal/31

->4Ga\ß

1 -a4G1c/31 -ACer

Gala (GL

2

b)

(GalNAc? 1 —>3Gal?l)—>4Galotl ->4Gal/31 -ACer

Central nervous system, kidney

Globo (GL4a)

GalNAc? 1 —>3Gala 1

->4Ga\ß

1 -a4G1c/31 -ACer

Kidney, heart, erythrocytes

Ganglio (GM1)

Gal/31 —>3GalNAc/3l ^4Gal/31 -a4G1c/3 1

^ C er

Central nervous system

Lactosyl ceramide (GL

2

a)

Gal/31 -a4G1c/31 —>Cer

Major glycolipid in most

non-neural tissue

Glucosyl ceramide (GLia)

Glc/3l—>Cer

Major neutral glycolipid in

central nervous system

Galactosyl ceramide (GLp,)

Gal/31—>Cer

Major neutral glycolipid in plasma

*The names on the first six lines are the prefixes used to designate the core sugars when naming glycolipids. For all the structures, the names in

parentheses are the old designations for the corresponding glycosylceramide. The only exception is GL2b, which stands for Gal-Gal-Cer, not for the

Gala tetrasaccharide.

tAlthough the Gala structure is shown as a tetrasaccharide, no Gala-type glycolipids having structures more complex than Gal-Gal-Cer (galabiosyl-

ceramide) have been purified from natural sources. Gal= Galactose, Glc = glucose, GalNAc = N-acetylgalactosamine, Cer = ceramide.

fThe tissues listed in this column are those in which relatively large amounts of glycolipid having the indicated structure are found. Many of these

compounds are also found in other tissues at lower concentrations.