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370 Current Bioactive Compounds 2012, 8, 370-409
Activity and Structure Elucidation of Ceramides
E. S. Elkhayat
a
*, G. A. Mohamed
a
and S. R. M. Ibrahim
b
a
Faculty of Pharmacy, Department of Pharmacognosy, Al–Azhar University, Assiut, 71524 Egypt;
b
Faculty of Phar-
macy, Department of Pharmacognosy, Assiut University, Assiut,71526 Egypt
Abstract: Ceramide, a derivative of sphingolipid breakdown products, acts as second messenger for multiple extracellular
stimuli including growth factors, chemical agents, and environmental stresses. They have been shown to be crtically in-
volved in various biological processes, including differentiation, senescence, cell-cycle arrest, proliferation, and apoptosis.
Ceramide molecules form distinct domains in the cell membrane, which may serve to re-organize cellular receptors and
signaling molecules. Because of their promising biological activities and applications, here we focus on: biosynthesis, ex-
istence, importance, and structure elucidation, as well as representative examples concerning their structure and activity.
Keywords: Ceramide, sphingolipid, biological activity, identification.
INTRODUCTION
Ceramide is a family of lipids that consist of sphingosine
linked to fatty acid via amide linkage [1]. The vast majority
of fatty acids are -hydroxylated. The polyunsaturated fatty
acids exist in certain testicular cells [2,3]. Ceramide plays
important role in organizing membrane structure as it has the
tendency to self-aggregate and segregate into membrane
microdomains [4]. For years, it was assumed that ceramide
was purely structural elements. This is now known to be not
completely true. Ceramide attracted substantial concern be-
cause of its contribution in vital biological processes such as
cell cycle arrest, apoptotic cell death, cellular proliferation
and inflammatory responses [5,6]. Such effects have been
attributed to the second messenger signaling capabilities of
this lipid. With a small hydroxy head group and two long
saturated hydrophobic chains, in addition to intermolecular
hydrogen bonding, ceramide packed tightly in bilayers and
promotes membrane rigidity [7].
Ceramide represent precursor of major sphingolipids,
such as sphingomyelin (SM), ceramides 1-phosphate (C1P),
and glucosylceramides (GlcCer) [8,9]. Sphingolipids them-
selves are the precursors to generate series of glycosphin-
golipids and gangliosides [10,11] (Fig. 1).
BIOSYNTHESIS OF CERAMIDES
New approaches in cell biology and the development of
in vivo models (e.g. yeast [12], Dorsophila [13], and geneti-
cally modified mice [14]), afforded the identification of dif-
ferent biosynthetic pathways for ceramide [15,16]. Several
efforts have described the basic engagement of major phos-
pholipids in biosynthesis and degradation of ceramide [4].
Ceramide could be generated by one of three main pathways;
de novo synthesis, through SM hydrolysis, or through sal-
vage pathway.
*Address correspondence to this author at the Faculty of Pharmacy, De-
partment of Pharmacognosy, Al–Azhar University, Assiut, 71524 Egypt;
E-mail: khayat71@yahoo.com
HO
NH
3
OH
Sphingosine
O
NH
3
OH
P HO
O
O
Sphingosine-1-phosphate
O
HN
OH
P HO
O
O
O Ceramide-1-phosphate
HO
HN
OH
O
Amide linked fatty acyl chain
O
HN
OH
P O
O
O
O
Sphingomyelin
N
Cerebroside
O
NH
O
OH
O
HO
HO
OH
OH
Fig. (1). Bioactive Sphingolipids
a. Sphingomyelin Hydrolysis (Sphingomyelinase)
In this pathway, ceramide was generated from hydrolysis
of SM induced by the effect of sphingomyelinase (SMase)
[17,18], which cleave SM to ceramide and phosphocholine.
SMases are stimulated in response to TNF- [19,20], fatty
acids ligand [21], or oxidative stress [22]. The SM hydroly-
sis has emerged as a major pathway of stress-induced cera-
mide generation. This pathway has been suggested to regu-
late SM and ceramide levels [23], as well as the activation of
NFB [24-26].
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