Atherosclerosis 154 2001 1 – 13
Review article
The sialylation of plasma lipoproteins
John S. Millar
Department of Medicine, Uni6ersity of Pennsyl6ania,
621
BRB IIIII,
421
Curie Boule6ard, Philadelphia, PA
19104
-
6160
, USA Received 22 February 2000; received in revised form 1 September 2000; accepted 13 October 2000
Abstract
Sialic acids are a family of amino sugars that are commonly found as terminal oligosaccharide residues on glycoproteins and glycolipids. Plasma lipoproteins are sialylated on their apolipoprotein and glycolipid constituents. The function of sialic acid on
apolipoproteins is not completely understood but has been associated with secretion, lipid-binding, and plasma clearance for some apolipoproteins. The sialic acid content of individual apolipoproteins can vary in response to physiological conditions while the
sialic acid content of individual sialylated glycolipids gangliosides is constant. Thus, the sialic acid content of plasma lipoproteins can differ considerably as a result of 1 variations in the sialylation of their apolipoprotein constituents, 2 variations in their
content of sialylated apolipoproteins and gangliosides, and 3 modifications of the sialic acid on lipoprotein constituents while circulating in plasma. The significance of sialic acid on lipoproteins is not fully understood although associations have been made
between sialic acid and charge very low density lipoprotein, lipoprotein solubility, receptor binding and uptake, and interactions with vascular matrix low density lipoprotein and Lpa and with cholesterol efflux high density lipoprotein. Further studies
identifying sites of sialylation on apolipoproteins and characterizing the structures of sialylated oligosaccharides will aid in determining the enzymes responsible for their sialylation. Manipulations of the sialylation of apolipoproteins and of the quantity
of apolipoproteins and gangliosides on lipoproteins will be useful methods in determining the role of lipoprotein sialic acid in the development of atherosclerosis. © 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Sialic acid; Gangliosides; Oligosaccharides; Very low density lipoprotein; Low density lipoprotein; High density lipoprotein; Lpa www.elsevier.comlocateatherosclerosis
1. Introduction
Sialic acids are a family of N- and O-substituted derivatives of neuraminic acid, an amino sugar Fig. 1
[1]. Over 40 different naturally occurring derivatives of sialic acid have been identified [2]. These are generally
found as terminal sugar residues on oligosaccharides of both glycoproteins and glycolipids [2]. The functions of
sialic acids in biological systems include conformational stabilization, protease resistance, charge, enhancement
of water binding capacity, cellular recognition, protein targeting, and developmental regulation [3]. The most
common sialic acid found on human plasma glyco- proteins and glycolipids is 5-N-acetylneuraminic acid
Fig. 1, frequently found in an a-2,3-linkage with galactose [1,2]. O-acetylated derivatives of neuraminic
acid are normally found in plasma of some mammalian species including mouse, rat, guinea pig, cow, and
horse. In humans O-acetylated derivatives are not normally found in plasma except during fetal develop-
ment [2,4]. These derivatives are also found in abun- dance in the plasma of patients with malignant
melanoma [2,4]. For the purposes of this manuscript the term ‘‘sialic acid’’ will refer to 5-N-acetylneuraminic
acid.
The majority of sialic acid in plasma is protein- and lipid-bound Fig. 2 with little occurring in the free
form [2,5]. Elevations in the plasma sialic acid concen- tration have been reported for both the protein- and
lipid-bound fractions [6]. Lipid-bound sialic acids have been shown to be elevated due to unregulated produc-
tion of gangliosides, the sialic acid-containing family of glycolipids [6]. An increase of protein-bound sialic acids
in plasma has also been observed in inflammatory disease, possibly as a result of elevations in plasma
levels of acute phase proteins, many of which are sialylated [7,8].
Studies relating sialic acid to the development of coronary heart disease CHD tend to fall into one of
Tel.: + 1-215-8985909; fax: + 1-215-5736725. E-mail address
:
jsmillarmail.med.upenn.edu J.S. Millar. 0021-915001 - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0021-91500000697-3
Fig. 1. Upper Basic molecular structure for derivatives of neu- raminic acid. Variable sites are represented by an ‘R’ with a subscript
indicating the carbon number to which different groups may be attached. Lower 5-N-acteylneuraminic acid, the most abundant
sialic acid derivative found in human plasma.
sion that individuals with low levels of lipoprotein-asso- ciated sialic acid are at increased risk of developing
CHD [12 – 14]. Despite this relationship the factors that control the content of lipoprotein-associated sialic acid
are not known.
The factors that influence the content of lipoprotein- associated sialic acid and its relationship to lipoprotein
metabolism will be the focus of this review. The discus- sion will begin with an overview of the sialic acid-con-
taining components on lipoproteins apolipoprotein apo, glycolipids and their contribution to the total
sialic acid content of a lipoprotein fraction, and end with the known effects that lipoprotein sialic acid has
on lipoprotein metabolism. Graphical representations of some of the terms used in this manuscript are shown
in Fig. 3.
2. Apolipoprotein sialic acid
