Download Lipidomics comes of age in nutrition and

Lipidomics comes of age in nutrition and
othertranslational sciences
A. Lipidomics and Nutrition
B. Examples
C. Additional perspectives
Alfred H. Merrill, Jr.
Schools of Biology, Biochemistry & Chemistry
and the Petit Institute for Bioengineering and Biosciences
Georgia Institute of Technology
Omic categories:
(partial list)
Genomics
(Epigenomics)
Transcriptomics
Proteomics
Glycomics
(posttranslational
modifications)
Gene
mRNA
miRNA
Protein
Protein-protein
interactions
Post-translational
modification(s)
Metabolomics
Metabolites
Cell functions & regulatory mechanisms
Embryogenesis to aging (disease)
Systems
Biology
Lipidomics
& Nutrition:
Nutrients
Toxins
etc.
Nutrition is a fundamental
component of systems
biology at all levels, and
especially the
metabolome.
Embryogenesis to aging (disease)
Systems
Biology
Genomics
(Epigenomics)
Transcriptomics
Proteomics
Glycomics
(posttranslational
modifications)
Gene
mRNA
miRNA
Protein
Protein-protein
interactions
Post-translational
modification(s)
Metabolomics
Metabolites
Cell functions & regulatory mechanisms
Omic categories:
(partial list)
J. Nutr. 1: 191, 1928.
Lipidomics
& Nutrition:
Nutrients
Toxins
etc.
The field of nutrition has
been concerned about the
question of how many
molecules are present and
the amounts for a long time.
Omic
categories:
recognize
the importance
Gene of
(partial
list)
metabolomics,
as indicated in
this opinion piece from 2002 that
Genomics
is still relevant today.
(Epigenomics)
mRNA
Transcriptomics
Proteomics
Glycomics
(posttranslational
modifications)
miRNA
Protein
Protein-protein
interactions
Post-translational
modification(s)
Embryogenesis to aging (disease)
J. Nutr. 1: 191, 1928.
Cell functions & regulatory mechanisms
Systems
Biology
…and was one of the first to
Environment
J. Nutr. 132: 2486–2487,
2002.
Nutrients
Toxins
etc.
Metabolomics
“Metabolomics does not have the luxury of a single class of analyte
nor a single mode
of analysis and the field of metabolomics will
Metabolites
continue to be driven by technological developments.”
Omic categories:
(partial list)
Genomics
(Epigenomics)
mRNA
Transcriptomics
Proteomics
Glycomics
(posttranslational
modifications)
Protein
Protein-protein
interactions
Post-translational
modification(s)
Metabolomics
Lipidomics
Metabolites
Cell functions & regulatory mechanisms
Systems
Biology
Rationale for lipidomics in nutrition:
Embryogenesis to aging (disease)
Lipids are one of the most structurally diverse,
multifunctional biomolecules, and may constitute the
largest
Gene “omic” category.
This presents both analytical and conceptual
challenges.
Environment
Nutrients
Toxins
etc.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
Better understanding of:
Digestion
Absorption
Transport
Metabolism
Factors impacting metabolism
Molecular function
An organism, as in
the cartoon here, is
basically an eating,
food processing, and
excretion machine.
GI microbiome metabolism/metabolites
Excretion
Lipidomics
ultimately wants
to understand the
correlations
between
consumption and
health & disease.
Levels
where
lipidomics has been/can be helpful to
There
are many
groups
already
measuring
large
nutrition
(and
some other translational disciplines)
numbers of compounds in
food and relating their
Better understanding of:
consumption to health.
molecular subspecies in food
(& the environment)
and the amounts consumed
Better understanding of:
Digestion
Absorption
Transport
Metabolism
Factors impacting metabolism
Molecular function
GI microbiome metabolism/metabolites
Advantages: Easy access; well established; reliable
Excretion
Disadvantages: For the most
part, covers only known nutrients
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
Lipidomics in nutrition and
Better understanding of: food research. Hyötyläinen
Digestion
T, Bondia-Pons I, Orešič M.
Absorption
Mol Nutr Food Res. 2013
Transport
Feb 15. PMID: 23413227
Metabolism
Factors impacting metabolism
Foodomics: a new
The field of nutrition has Molecular function comprehensive approach to
food and nutrition. Capozzi
been concerned about the
GImany
microbiome metabolism/metabolites
F, Bordoni A.
question of how
Genes Nutr. 8:1-4 (2013)
molecules are present and
Excretion
the amounts for a long time.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
Better understanding of:
Digestion
Absorption
Transport
Anal Chem. 85:1114-23 (2013).
Metabolism
Factors impacting metabolism
Molecular function
GI microbiome metabolism/metabolites
Excretion
The topic even encompasses
the fecal lipidome.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
Better understanding of:
Digestion
Absorption
Transport
Metabolism
Factors impacting metabolism
Molecular function
GI microbiome metabolism/metabolites
Excretion
The field of sphingolipidomics
began with the discovery of
sphingosine.
The sphingolipid
backbone(s)
Sphingoid bases
“Sphingosines”
(named for “…the many
enigmas which it presented
to the inquirer…”)
1884
1881
N-acyl-sphingoid bases
(“Ceramides”)
J. L. W. Thudichum
Cookery. Its Art and Practice
(1895)
Thudichum was also
very interested in food
chemistry.
Physiologic deduction proves that perfect cookery is the greatest economy
…[for]… production of the highest physiological force…
It is believed and hoped that the medical profession will find in this work
many materials to assist them in dietetic disquisitions, and in the synthesis
of rules to give into the hands of patients or their providers. Such advice is
often asked for, and is always well received; and this experience has been
one of the motives for the composition of this treatise.
p. vi-vii
Levels where lipidomics has been/can be helpful to
Usual
mammalian
nutrition
(and some other translational disciplines)
sphingolipids.
The first step is a better
understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
OH
NH2
Spisulosine (1-deoxysphinganine)
OH
NH2
Obscuraminol
HO
O
HO
O
O
O
O
Examples of novel
O
compounds
from
O
HO
OHO
other sources.
OH
OH
Fumonisin B1
OH
NH2
Biodiversity of sphingoid bases
("sphingosines") and related amino
alcohols.
ST Pruett et al.,
J Lipid Res. 49:1621-39 (2008).
Sphingolipid and glycosphingolipid
metabolic pathways in the era of
sphingolipidomics.
AH Merrill Jr. Chem Rev
111:6387-422 (2011).
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
OH
Spisulosine (1-deoxysphinganine)
ES-285
NH2
Spisula polynyma
1-deoxysphinganines were
first found in other
organisms.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
OH
Spisulosine (1-deoxysphinganine)
ES-285
NH2
Spisula polynyma
The marine compound spisulosine, an inhibitor of cell proliferation, promotes the
disassembly of actin stress fibers. R. Cuadros et al., Cancer Lett. 152:23-9 (2000).
Phase I dose-escalating study of ES-285 given as a three-hour intravenous
infusion every three weeks in patients with advanced malignant solid tumors.
C. Massard et al., Invest New Drugs. 30:2318-26 (2012).
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
OH
1-deoxysphinganine (-osine)
NH2
pmol/g dry weight
pmol/g dry weight
Predicted site of N-acylation
N-acyl-chain derivatives of 1-deoxysphinganine
(1-deoxyDHCer) and 1-deoxysphingosine (1-deoxy-Cer) in beef and octopus.
They are usually present as the N-acyl-derivatives, and in many foods.
These data are from ongoing studies of novel 1-deoxy-sphingolipids in food
OH
NH
2
1-deoxysphinganine (-osine)
Site of N-acylation
Better understanding of:
molecular subspecies in food
(& the environment)
and the amounts consumed
Sum of the analyzed N-acyl-chain derivatives of 1-deoxysphinganine
(1-deoxyDHCer) and 1-deoxysphingosine (1-deoxy-Cer) in the foods shown.
From Ongoing studies of novel 1-deoxy-sphingolipids in food
Sphingolipids in selected foods and yearly consumption per capita
Product
Sphingolipid content
Consumption per capita
The presence
_________________________________________________________________________
of
mmol/kg
mmol/year (g/year)
sphingolipids
Modulation of intracellular betain foodDairy products
38.5
catenin localization and intestinal
appears to
Milk (3.5%)
0.16
5.76
tumorigenesis in vivo and in vitro
Lowfat Milk (<2%) 0.09
5.49
have an
Cheese (29%)
1.33
15.9
by sphingolipids.
impact on
Frozen dairy (11%) 0.50
7.04
EM Schmelz et al., Cancer Res
cancer.
Butter
0.46
0.92
61:6723-9 (2001)
Eggs
2.25
14
Total meat products
Beef & veal
Chicken & turkey
Fish0.50
Vegetables
Potato
Tomato
Soybeans
Fruits and nuts
Cereals
0.39
0.39 to 0.53
0.13
0.04 to 2.4
0.69
0.42
2.4
0.07 to 0.8
0.58
34.3
11.3
14.0
0.9
8.1 to 34
4.1
1.7
n.a.
3.2
38
Suppression of breast xenograft
growth and progression in nude
mice: implications for the use of
orally administered sphingolipids
as chemopreventive agents
against breast cancer.
KW Simon et al., Food Funct.
1:90-8 (2010).
Total per year:
153 to 181
116 to 139
_________________________________________________________________________
Vesper et al., J. Nutr.129: 1239-1250 (1999).
HO
What is (are) factors
that might limit the
effectiveness of
dietary sphingolipids
(i.e., the sphingoid
bases after digestion)
as anti-cancer
agents?
HO
Absorption of
sphingoid bases
from complex
sphingolipids
NH3(+)
R
HO
HO
NH3(+)
HO
NH2
HO
R
R
R
R
HO
NH3(+)
HO
HO
HO
The “usual” types of
sphingoid bases are
mainly degraded in
the intestinal cells.
Intracellular
targets:
(-) cancer
(+) cancer
HO
NH2
Sphingosine
kinase
R
Degraded to fatty
aldehyde +
NH3(+)
ethanolamine-P
O
PO3=
Blood
Intestinal lumen
HO
HO
HO
NH3(+)
R
versus:
Absorption of sphingoid bases
w/o hydroxyl at carbon 1
HO
NH2
HO
HO
NH3(+)
HO
HO
HO
NH2
R
HO
NH2
NH3(+)
NH2
R
HO
NH3(+)
HO
R
R
R
HO
NH3(+)
NH2
R
R
HO
R
HO
R
R
Absorption of
sphingoid bases
from complex
sphingolipids
NH3(+)
R
Bound to albumin and RBC
NH3(+)
Intracellular
targets:
(-) cancer
(+) cancer
R
R
HO
NH3(+)
HO
HO
Sphingosine
kinase
R
HO
O
PO3=
NH3(+)
HO
NH2
Degraded to fatty
aldehyde +
ethanolamine-P
1-deoxysphingoid bases are
more likely to be Blood
absorbed.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
&
Metabolism
Factors impacting metabolism
Where did we first note 1Molecular function
deooxysphingoid bases in
mammals?
OH
N-acyl-metabolites
NH2
Spisulosine (1-deoxysphinganine)
HO
O
HO
O
O
O
OH
O
HO
O
O
OHO
OH
Fumonisin B1
OH
NH2
Ceramide
synthase
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
&
Metabolism
Factors impacting metabolism
Molecular function
OH
N-acyl-metabolites
Spisulosine (1-deoxysphinganine)
NH2
Ceramide
synthase
Origin of 1-deoxy-sphingoid bases? Utilization of both Ser and Ala by
serine palmitoyltranserease, the first enzyme of sphingolipid biosynthesis.
While wild type SPT utilizes Ser>Ala, Hornemann et al. (2009) have found
that SPT muations in human sensory neuropathies (HSN) result in
elevated Ala utilization and biosynthesis of 1-deoxy-sphingolipids, which
appear to be major contributors to the neuropathology.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Better understanding of:
molecular subspecies in food
&
Metabolism
Factors impacting metabolism
Molecular function
Glycolysis, TCA cycle, transaminations
Pyruvate
One carbon
pool
Glycine
Serine
Alanine
Serine palmitoyltransferase
Sphinganine
OH
OH
R
NH2
OH
R
1-(Desoxymethyl)sphinganine
OH
R
NH2
1-Deoxysphinganine
NH2
N-acylation (1-deoxy…)-dihydroceramides then
desaturation (1-deoxy…)-ceramides
Thus, the factors that govern the
amounts of 1-deoxy- sphingolipids
that are made are de novo:
a)  Precursor availability
b)  SPT wild type and/or
mutations
Different sphingoid bases are made
when the precursor supply is
modulated, or when SPT is mutated.
Levels where lipidomics has been/can be helpful to
nutrition (and some other translational disciplines)
Implications? Can also be
neurotoxic
Glycolysis, TCA cycle, transaminations
Pyruvate
One carbon
pool
Glycine
Serine
Alanine
Serine palmitoyltransferase
Sphinganine
OH
J Clin Invest. 121:4735–4745 (2011)
OH
R
NH2
OH
R
1-(Desoxymethyl)sphinganine
OH
R
NH2
1-Deoxysphinganine
NH2
N-acylation (1-deoxy…)-dihydroceramides then
desaturation (1-deoxy…)-ceramides
Endogenous vs exogenous 1-deoxysphingoid bases?
Up to this point, we have discussed only a few of the simple backbone
variants, whereas, the major species in mammals are N-acyl-metabolites
and beyond, with >500 headgroup elaborations
(download available at www.sphingomap.org)
26
SPT
Serine +
Palmitoyl-CoA
Reductase
3-Ketosphinganine
(3-Keto-m18:0)
Sphinganine (d18:0)
SMS
d18:0
c18:0
DHCerP
d18:0
c20:0
DHSM
d18:0
c22:0
DHSM
d18:0
c20:0
DHCerP
d18:0
c22:0
DHCerP
d18:0
c24:1
DHSM
d18:0
c24:1
DHCerP
d18:0
c24:0
DHSM
d18:0
c24:0
DHCerP
d18:0
c26:1
DHSM
d18:0
c26:1
DHCerP
d18:0
c26:0
DHSM
d18:0
c26:0
DHCerP
d18:0
c18:0
GlcDH
d18:0;
c20:0
DHCer
d18:0
c18:0
GalDH
SM
GalCer
synthase
d18:1
c18:0
Glc
d18:1
c16:0
Gal
Sulfate------ Gal
(ST)
d18:1
c16:0
Galβ1------- 4Glc
(LacCer) d18:1
c16:0
d18:0
c20:0
GalDH
SM
CerP
d18:0
c22:0
GlcDH
d18:0
c22:0
GalDH
d18:0;
c24:1
DHCer
d18:0
c24:1
GlcDH
d18:0
c24:1
GalDH
d18:0;
c24:0
DHCer
d18:0
c24:0
GlcDH
d18:0
c24:0
GalDH
d18:0;
c26:1
DHCer
d18:0
c26:1
GlcDH
d18:0
c26:1
GalDH
d18:0;
c26:0
DHCer
d18:0
c26:0
GlcDH
SM
CerP
SM
CerP
SM
CerP
SM
CerP
d18:0
c26:0
GalDH
SM
CerP
3 unique
samples
(ranging
to 100 µL)d18:1;
d18:0;
d18:1;
d18:1; from 1 d18:1;
c20:0
c22:0
c24:1
c24:0
c26:1
and sample
preps
Cer
Cer
Cer
Cer
Cer
6 unique LC-MS/MS analyses
CERK
d18:1;
c16:0
Cer
d18:0
c20:0
GlcDH
d18:0;
c22:0
DHCer
Dihydroceramide desaturases
Analysis of more
complex mammalian sphingolipids by LC-MS/MS
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
d18:1
(from
3-ketosphinganine
simple
& sulfatides):
c18:0
c20:0
c22:0
c24:1
c24:0 gangliosides
c26:1
c26:0
c18:0
c20:0
c22:0 through
c24:1
c24:0
c26:1
c26:0
d18:1
c16:0
CerP
SMS
d18:0;
c18:0
DHCer
GalCer
synthase
d18:0
c16:0
GalDH
d18:1
c16:0
SM
d18:1
c16:0
Glc
d18:0
c18:0
DHSM
CerS3 (> c24)
CERK
d18:0;
c16:0
DHCer
d18:0
c16:0
GlcDH
GlcCer
synthase
Sphingosine
(d18:1)
Ceramidases
GlcCer
synthase
Sphingosine 1-P (d18:0-P)
CerS2 (c22,24)
CerS4 (c20 + 2)
CerS1 (c18)
d18:0
c16:0
DHCerP
SphK
NH2
Hexadec(an/en)al
+ Ethanolamine-P
Lyase
SphK
CerS5 (c16) &
6 (c14 & 16)
d18:0
c16:0
DHSM
Sphinganine 1-P (d18:0-P)
OH OH
d18:0;
c18:0
Cer
d18:1
c20:0
Glc
d18:1
c18:0
Gal
d18:1
c22:0
Glc
d18:1
c20:0
Gal
d18:1
c22:0
Gal
d18:1
c24:1
Glc
d18:1
c24:1
Gal
d18:1
c24:0
Glc
d18:1
c24:0
Gal
d18:1
c26:1
Glc
d18:1
c26:1
Gal
CerP
d18:1;
c26:0
Cer
d18:1
c26:0
Glc
plus tissue slices for tissue imaging mass spectrometry.
Sulfate------ Gal
(ST)
d18:1
c18:0
Galβ1------- 4Glc
(LacCer) d18:1
c18:0
Sulfate------ Gal
(ST)
d18:1
c20:0
Sulfate------ Gal
(ST)
d18:1
c22:0
Sulfate------ Gal
(ST)
d18:1
c24:1
Sulfate------ Gal
(ST)
d18:1
c24:0
Sulfate------ Gal
(ST)
d18:1
c26:1
d18:1
c26:0
Gal
Sulfate------ Gal
(ST)
d18:1
c26:0
MC Sullards et al., Biochim Biophys Acta 1811:838-53 (2011)
Galβ1------- 4Glc
(LacCer) d18:1
c20:0
Galβ1------- 4Glc
(LacCer) d18:1
c22:0
Galβ1------- 4Glc
(LacCer) d18:1
c24:1
Galβ1------- 4Glc
(LacCer) d18:1
c24:0
Galβ1------- 4Glc
(LacCer) d18:1
c26:1
Galβ1------- 4Glc
(LacCer) d18:1
c26:0
Single phase
extraction
(w/internal
standards)
Biological
sample
Analytes
Column/MS
Sphingoid
bases
S1P, Sa1P
Cer1P
Sulfatides
Reverse phase
column (C18)
QQQ or
Qtrap
Gangliosides
Organic phase
Extraction
(w/internal
standards)
Ionization
mode
+
+
-
OrbiTrap
Cer, HexCer,
Normal phase
LacCer, SM,
column (LC-NH2)
(Cer1P,
QQQ or QTrap
Sulfatides)
Normal phase
GlcCer,
column (LC-Si)
GalCer
QQQ or QTrap
Normalization aliquot (DNA, Protein, Cell #, etc)
+
+
For complex glycoSL we
are using the Thermo
LTQ Orbitrap XL
& Eksigent NanoLC 2D
a)  Hybrid Linear Ion
trap / Orbitrap – 2
instruments that can
be operated in
series or parallel
b)  Orbi – 10-100K
resolution, < 3ppm
mass accuracy
c)  LTQ XL - MS1-10
for molecular
connectivity
relationships
d)  CID, PQD, HCD,
ETD
e)  2D Liquid
Chromatography SAX / RP
Merrill, A. H., Jr. Chem. Rev. 111, 6387-6422 (2011)
Relative Abundance
GM1 – h38:1, -1.2 ppm
1588.8926
100
90
1589.8951
80
NL:
7.45E4
mcs0030_120411133232
#1499-1516 RT:
36.42-36.83 AV: 18 T:
FTMS - p ESI Full ms
[500.00-2000.00]
70
60
50
1590.8989
40
30
20
10
1591.8997
0
NL:
4.02E5
1588.8945
100
C 75 H 134 N 3 O 32 :
C 75 H 134 N 3 O 32
pa Chrg 1
90
1589.8978
80
70
60
50
40
Example spectra
1590.9012
30
20
1591.9046
10
0
1587
1588
1589
1590
1591
m/z
1592
1593
1594
NL:
1.22E5
mcs0030_120411133232
#1483-1500 RT:
36.03-36.45 AV: 18 T:
FTMS - p ESI Full ms
[500.00-2000.00]
925.4747
100
80
60
933.4721
926.4780
40
934.4753
926.9793
20
Relative Abundance
0
100
934.9769
931.5184
927.4810
NL:
3.56E5
925.4751
925.9768
80
C 84 H 146 N 4 O 40 :
C 84 H 146 N 4 O 40
pa Chrg 2
GD1 – h35:1, -0.4ppm
60
926.4785
40
20
926.9802
0
100
NL:
3.55E5
933.4726
933.9743
C 84 H 146 N 4 O 41 :
C 84 H 146 N 4 O 41
pa Chrg 2
GD1 – 2h35:1, -0.5ppm
80
60
934.4759
40
20
934.9776
0
923
924
925
926
927
928
929
930
m/z
931
932
933
934
935
936
Relative Abundance
NL:
8.59E4
mcs0030_120411133232
#1503-1521 RT:
36.52-36.96 AV: 19 T:
FTMS - p ESI Full ms
[500.00-2000.00]
GT1 – h36:2, -0.7ppm
1070.5161
100
90
1070.0142
80
70
1071.0175
60
50
40
1071.5195
30
20
1072.0215
10
0
100
1070.0150
NL:
3.17E5
1070.5167
C 95 H 161 N 5 O 48 :
C 95 H 161 N 5 O 48
pa Chrg 2
90
80
70
60
1071.0184
50
40
30
20
1071.5200
10
1072.0205
0
1068.5
1069.0
1069.5
1070.0
1070.5
1071.0
m/z
1071.5
1072.0
1072.5
1073.0
1073.5
mcs0031_120412122915
4/12/2012 12:29:15 PM
Add liquid chromatography
GM2
RT: 49.93 - 55.03
100
Relative Abundance
90
52.42
52.95
GM1
80
GM3
53.22
53.05
70
NL:
1.13E6
m/z=
1207.71961207.8007 MS
mcs0031_12041212
2915
NL:
2.34E6
m/z=
1410.79881410.8953 MS
mcs0031_12041212
2915
NL:
3.36E6
m/z=
1572.83121572.9470 MS
mcs0031_12041212
2915
53.32
60
50
40
30
20
10
0
50.0
50.5
51.0
mcs0031_120412122915 #2145-2202 RT: 52.13-53.51
T: FTMS - p ESI Full ms [500.00-2000.00]
51.5
52.0
52.5
Time (min)
53.0
53.5
54.5
55.0
AV: 58 NL: 6.82E5
1572.8950
100
Relative Abundance
54.0
90
80
70
1410.8434
60
808.9471
50
40
1207.7650
30
20
10
727.9207
1382.8129
0
600
700
800
900
1000
1100
1200
1300
m/z
1400
1500
1600
1700
1800
1900
2000
RT: 36.83 - 64.80
NL:
3.41E7
TIC MS
mcs0031_1
2041212291
5
48.36
100
GM1
95
90
85
36:1
80
47.94
75
Relative Abundance
70
65
38:1
60
55
37:1
50
45
52.42
40
h36:0
35
36:0
30
34:1
25
40:1
38:0
36:2
52.95
20
53.05
44.10
15
53.20
50.38
10
5
58.30
54.65
45.10 45.15
43.28
55.24
55.31
57.06
58.84
57.13
58.91
60.59
60.66
59.98
50.86
61.73
0
38
40
42
44
46
48
50
52
Time (min)
54
56
58
60
62
64
A method to
assist in
40 category
identification
Kendrick Mass Defect Plot
GD1 + HexNAc
30 20 RKMD GM3
10 GD1
GM3
0 0 -­‐10 -­‐20 200 400 600 800 1000 1200 1400 1600 1800 2000 GM2
GM1
GM1 + Fuc
-­‐30 -­‐40 Complex glycosphingolipids are also highly relevant to nutrition, as
illustrated by interest in milk gangliosides.
Internat’l J. Mass Spectrometry 305:138–150 (2011)
36
Lipidomics comes of age in nutrition and other
translational sciences
A. Lipidomics and Nutrition
B. Examples: Sphingolipids
C. Additional perspectives
The lipidome is much bigger than one might have thought.
Wonderful tools are on hand, but more are needed.
There is much left to learn—even new compounds to be found.
Potentially important discoveries are found around almost every corner.
(join the fun)