GLYCOSPHINGOLIPIDS: Lacto-series

When was lacto-series discovered?

The first clear evidence for the existence of lacto-series glycolipids was the
isolation and characterization of sialosyl-lacto-N-neotetraosylceramide by
Kuhn and Wiegandt in 1964
Subsequently, another lacto-series of glycolipids substituted with a fucose
residue found to accumulate in some human adenocarcinomas
o the structure was identified as lacto-N-fucopentoase (III) ceramide
an extensively purified glycolipid fraction with blood group A, B, and H
activities was found to compromise lacto-series glycolipids containing
N-acetyl glucosamine and fucose
A ceramide tetrasaccharide called paragloboside was identified as lacto-Nneotetraosylceramide
Other lacto-series compounds were then found, including ceramide
pentasaccharide from rabbit erythrocytes and fucose- and glucosaminecontaining glycolipid of gastrointestinal mucosa.
Consequently, a number of glycolipids have been isolated and characterized
as blood groups ABH, Lewis, Ii, and P1 antigens all of which possess lactoseries structures.
Lacto-series constitute the major glycolipid component of various tissues and
organs and its sialosyl derivatives represent the major ganglioside of
extraneural tissues
However, a small quantity of lacto-N-fucopentaosyl(III)ceramide and its
sialosyl derivative were found in brain
The carbohydrate chains of lacto-series glycolipids are extensively
substituted with fucosyl, sialosyl, and alpha or beta-galactosyl, and with a
repeating Gal4GlcNAc structure
Combinations of these substitutions also occur resulting in a large variety of
glycolipid structure.

What constitutes the lacto-series?

Have the same first two sugars with other long carbohydrate chain neutral
glycosphingolipids lactosylceramide is the starting material for synthesis of
these compounds
When another galactosamine is linked to lactosylceramide by a (1 3)
linkage, lacto- and lactoneo-series glycolipids are produced
This trihexosylceramides can be further elongated by addition of one or
several galactose or N-acetylgalactosamines.
Another is Gal-GlcNAc-Gal-Glc-ceramide from lactosylceramide (L c4Cer).
They are blood-group-active lipids.

 Lactosylceramide (LacCer) It is the most important and abundant of the

diosylceramides is -D-galactosyl-(14)--D-glucosyl-(11)-ceramide (Gal14Glc1Cer) and the core structure of Lacto-series.

Where can they be found?

Are more evenly distributed in mammalian tissues

Are ubiquitous membrane components, presumably in the leaflet of the
membranes
GSLs with core carbohydrate chains of the lacto- and lactoneo-types
represent most of the blood-group-active glycolipids.
They are in erythrocyte membranes and plasma membranes of most animal
cells, especially those originating from bone marrow and spleen.
They serve as cell surface antigens and as markers appear to play a vital role
in cell recognition and cell-cell interaction.
Lacto-series glycolipids are prominent in secretory organs

What enzymes affect them?

Many of these compounds contain L-fucose attached to the terminal

galactose by a (1->2) linkage
Thus, fucosyltransferase plays a unique role in the synthesis of these
compounds
Some of these compounds contain sialic acid, which indicates the
participation of sialyltransferase in their biosynthesis
However, our knowledge of the synthesis of these compounds is meager.

How are they synthesized?

As with the long chain GSLs, our lack of information is due to the rather poor
substrate specificities if the various glycosyltransferases, and in addition, the
difficulty in isolating these complex glycolipids.
The biosynthesis of this series begins with the addition of an Nacetlyglucosamine to lactosylceramide by a (1->3) linkage to form
lactotriosyl ceramide
The first triose in the lacto category, Lc3 (GlcNAc1-3Gal1-4Glc1Cer), is
important for embryonic development especially in the brain.
2

What is the neolacto-series?

Oligoglycosylceramides of the neolacto-series contain alternating residues of

1,3-substituted galactose and 1,4-substituted N-acetylglucosamine, i.e. Nacetyllactosamine units.
At least 15 types are known with both linear and branched structures and
they can be are heavily substituted with fucose moieties.
There are some less well-characterized forms that contain up to 50
carbohydrate groups. They are important in that they are associated with
blood group A, B, H and other activities.
Most of these lipids function as antigens, and some are associated with
specific carcinomas. A terminal N-acetylgalactosamine residue is essential for
group A activity, for example. Some of these lipids have distinctive ceramide
structures including phytosphingosine and hydroxy acids.
Neolacto-series glycolipids are common on certain hematopoietic cells
including leukocytes.

Some examples of structures

GLYCOSPHINGOLIPIDS: Introduction

Glycosphingolipids (GSLs) are a type of glycolipid. They are found in the cell
membranes of organisms from bacteria to man, and are the major glycans of
the vertebrate brain, where more than 80% of glycoconjugates are in the
form of glycolipids.
The first glycolipid to be structurally characterized was galactosylceramide
(GalCer). Among the simplest of glycolipids, it is also one of the most
abundant molecules in the brain. It consists of a single galactose residue in
glycosidic linkage to the C-1 hydroxyl group of a lipid moiety called ceramide.
Action types are: Transregulation: opposing plasma membrane and Cis
regulation: same plasma membrane.

The biological functions of glycosphingolipids are related to the enormous

diversity of structures in both parts of the molecule i.e. the hydrophobic
ceramide and hydrophilic saccharide chain.
According to the biophysical properties, they form rather rigid structures in
cell membranes but their structural variety allows numerous specific
interactions e.g. lipid-lipid, lipid-protein, and carbohydrate-carbohydrate.
Biological function: Maintenance of neuronal function, Cellcell recognition,
Signal transduction, Skin permeability
The location of cellular sphingolipids is predominantly on the outer leaf of the
plasma membrane and the luminal surface of intracellular vesicles and
compartments.
Because of their saturated nature and their potential for hydrogen bonding
and dipolar interactions they tend to form membrane microdomains or rafts
together with cholesterol and specific proteins (e.g. GPI-anchored proteins).
While the existence of these structures continues to be discussed, other
evidence suggests that these specific membrane domains are engaged in
many cellular functions e.g. sorting processes, signaling, cell-cell recognition,
and other types of interactions, the mechanisms of which are not clearly
understood.

GSL related diseases