Drug redeployment to kill leukaemia and lymphoma cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids

Andrew D. Southam1*, Farhat L. Khanim1, Rachel E. Hayden1, Julia K. Constantinou1, Katarzyna Koczula2, Robert H. Michell1, Mark R. Viant1, Mark T. Drayson3 and Chris M. Bunce1.

1 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

2 School of Cancer Sciences, University of Birmingham, Birmingham, UK

3 School of Immunity and Infection, University of Birmingham, Birmingham, UK

*Corresponding author: Dr Andrew D. Southam

Phone: +44(0)121 414-8680

FAX: +44(0)121 414-5925

Email: A.D.Southam@bham.ac.uk

Running title: Anti-lipogenic leukaemia therapy targets SCD1

Supplemental Materials and Methods

Mass Spectrometry – SIM stitch

Data were collected using the SIM stitch approach (Southam, Payne et al. 2007) and each sample was collected in triplicate. In all cases a start delay of 30 s was used and individual SIM windows were acquired for 15 s each. Methods used: (1) polar negative ion 60-720 m/z, 9 × 100 m/z windows, 30 m/z overlap, (2) lipids positive and negative ion modes 150-1000 m/z, 6 × 200 m/z windows, 30 m/z overlap. Spectra were calibrated using the accurate masses of peaks present in the extracts (Tables S1-S4).

Table S1: Peaks used for the calibration of mass spectral data sets related to the Materials and Methods section. Accurate masses of peaks used for mass spectral calibration for direct infusion negative ion lipid analysis. Key: LPE – lysophosphatidylethanolamine; LPC – lysophosphatidylcholine; PE – phosphatidylethanolamine; PC – phosphatidylcholine; PI – phosphatidylinositol

Accurate m/z

Name

Ionform

Formula

480.3095651

LPE(18:0)

[M-H]-

C23H47NO7P-

582.3776447

LPC(18:0)

[M+OAc]-

C28H53NO9P-

716.5235808

PE(34:1)

[M-H]-

C39H75NO8P-

742.5392309

PE(36:2)

[M-H]-

C41H77NO8P-

744.5548810

PE(36:1)

[M-H]-

C41H79NO8P-

790.5603602

PC(32:1)

[M+OAc]-

C42H81NO10P-

816.5760103

PC(34:1)

[M+OAc]-

C44H83NO10P-

863.5655052

PI(36:1)

[M-H]-

C45H84O13P-

885.5498551

PI(38:4)

[M-H]-

C47H82O13P-

889.5811552

PI(38:2)

[M-H]-

C47H86O13P-

Table S2: Peaks used for the calibration of mass spectral data sets related to the Materials and Methods section. Accurate masses of peaks used for mass spectral calibration for MSMS-stitch negative ion lipid analysis. Key: PC – phosphatidylcholine; PS – phosphatidyserine

Accurate m/z

Name

Ionform

Formula

673.4813816

PS(34:1)

[M-C3H6NO2]-

C37H70NO10P-

701.5126818

PS(36:1)

[M-C3H6NO2]-

C39H74NO10P-

718.5392309

PC(32:0)

[M-CH3]-

C39H77NO8P-

716.5235808

PC(32:1)

[M-CH3]-

C39H75NO8P-

744.5548810

PC(34:1)

[M-CH3]-

C41H79NO8P-

770.5705310

PC(36:2)

[M-CH3]-

C43H81NO8P-

Table S3: Peaks used for the calibration of mass spectral data sets related to the Materials and Methods section. Accurate masses of peaks used for mass spectral calibration for direct infusion positive ion lipid analysis. Key: LPC – lysophosphatidylcholine; PC – phosphatidylcholine; DAG – diacylglycerol; TAG – triacylglycerol.

Accurate m/z

Name

Ionform

Formula

522.3554173

LPC(18:1)

[M+H]+

C26H53NO7P+

524.3710674

LPC(18:0)

[M+H]+

C26H55NO7P+

584.5248508

DAG(32:1)

[M+NH4]+

C35H70NO5+

612.5561510

DAG(34:1)

[M+NH4]+

C37H74NO5+

610.5405009

DAG(34:2)

[M+NH4]+

C37H72NO5+

734.5694330

PC(32:0)

[M+H]+

C40H81NO8P+

732.5537830

PC(32:1)

[M+H]+

C40H79NO8P+

758.569433

PC(34:2)

[M+H]+

C42H81NO8P+

760.5850831

PC(34:1)

[M+H]+

C42H83NO8P+

822.7545166

TAG(48:1)

[M+NH4]+

C51H100NO6+

848.7701667

TAG(50:2)

[M+NH4]+

C53H102NO6+

850.7858168

TAG(50:1)

[M+NH4]+

C53H104NO6+

874.7858168

TAG(52:3)

[M+NH4]+

C55H104NO6+

876.8014668

TAG(52:2)

[M+NH4]+

C55H106NO6+

900.8014668

TAG(54:4)

[M+NH4]+

C57H106NO6+

902.8171169

TAG(54:3)

[M+NH4]+

C57H108NO6+

904.8327670

TAG(54:2)

[M+NH4]+

C57H110NO6+

Table S4: Peaks used for the calibration of mass spectral data sets related to the Materials and Methods section. Accurate masses of peaks used for mass spectral calibration for direct infusion negative ion polar analysis.

Accurate m/z

Name

Ionform

Formula

145.0618662

Glutamine

[M-H]-

C5H9N2O3-

173.1043997

Arginine

[M-H]-

C6H13N4O2-

215.0327901

Glucose

[M+Cl]-

C6H12O6Cl-

239.0772414

Glucose

[M+OAc]-

C8H15O8-

346.0558097

Adenosine monophosphate

[M-H]-

C10H13N5O7P-

Mass Spectrometry – MSMS-stitch

Figure S1: Schematic showing the method for the MSMS-stitch technique related to the Materials and Methods section. Ions were isolated in 60 m/z wide windows in the ion trap (red lines). All ions in the window were fragmented by collision induced dissociation (CID, with a collision-energy of 80 eV). The daughter fragments were recorded in 100 m/z wide windows (blue lines) using the high resolution FT-ICR detector. Fragmentation and detection windows were stepped through higher m/z values, until a 670-970 m/z range had been fragmented and a 600-910 m/z range detected. The detected windows were then stitched together to create a complete spectrum (Southam, Payne et al. 2007). The peaks of interest in the resulting spectrum were neutral loss of methylacetate (C3H6O2) from phosphatidylcholine with an acetate adduct, and neutral loss of serine minus H2O (C3H5NO2) from phosphatidylserine.

Supplemental Results

Table S5: Mass spectrometry lipidomics data related to the “BaP treatment of acute myeloid leukaemia (AML) cell lines perturbs the phospholipidome” results section (see attached pdf). Negative ion mass spectrometry (phospholipid) analysis of lipid extracts from HL60 and K562 cells after 24 hr BaP treatment (0.5 mM bezafibrate, BEZ, and 5 µM medroxyprogesterone acetate, MPA). (a) HL60 cells analysed by direct infusion mass spectrometry (DIMS), (b) HL60 cells analysed by MSMS-stitch DIMS (Figure S1), (c) K562 cells analysed by DIMS and (d) K562 cells analysed by MSMS-stitch DIMS.

Table S6: Mass spectrometry lipidomics / metabolomics data related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section (see attached pdf). Negative ion DIMS (polar extract) analysis of glycerol 3-phosphate in (a) HL60 cells and (b) K562 cells treated with BaP for 24 hours. Positive ion DIMS (glycerolipid) analysis of lipid extracts from (c) HL60 and (d) K562 cells after 24 hr BaP treatment.

Table S7: Mass spectrometry 13C-glucose tracer lipidomics data related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section (see attached pdf). DIMS analysis of free fatty acids and phospholipids from lipid extracts from HL60 cells that have been treated with BaP, BEZ alone (0.5 mM) and MPA alone (5 µM) for 24 hours in the presence of 1-13C D-glucose.

Table S8: Mass spectrometry 13C-glucose tracer lipidomics phosphatidylcholine data related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section. DIMS analysis of phosphatidylcholine species from HL60 cells that have been treated with BaP, BEZ alone (0.5 mM) and MPA alone (5 µM) for 24 hours in the presence of 1-13C D-glucose. This table shows only 13C data that has come from 13C-glucose. The m/z is of the 12C peak and is in this table purely for peak annotation purposes only. MS/MS identifications are detailed in Figure S2. All data shown is n=4.

m/z found

Putative identification

Identification by MS/MS

Mean peak intensity

t-test relative to control

Fold change relative to control

Putative ID

m/z of ID

ppm error

Con

BaP

Bez

MPA

BaP

Bez

MPA

BaP

Bez

MPA

690.50794

PC(30:0)

690.50800

0.087

PC(16:0/14:0)

46912

44212

43049

49494

0.125

0.194

0.426

0.94

0.92

1.06

688.49229

PC(30:1)

688.49247

0.261

 

19209

17946

18532

22476

0.199

0.440

0.024

0.93

0.96

1.17

718.53916

PC(32:0)

718.53955

0.543

PC(16:0/16:0)

38988

31411

34880

38001

0.022

0.220

0.732

0.81

0.89

0.97

716.52350

PC(32:1)

716.52331

-0.265

PC(16:0/16:1) PC(14:0/18:1)

201234

145933

174826

205698

0.005

0.028

0.718

0.73

0.87

1.02

714.50793

PC(32:2)

714.50819

0.364

 

20564

13561

15209

19529

0.002

0.003

0.457

0.66

0.74

0.95

744.55481

PC(34:1)

744.55427

-0.725

PC(16:0/18:1)

491054

340625

391266

461771

0.002

0.017

0.416

0.69

0.80

0.94

742.53932

PC(34:2)

742.53939

0.094

PC(16:1/18:1)

139665

98546

109285

146265

0.001

0.010

0.466

0.71

0.78

1.05

740.52377

PC(34:3)

740.52399

0.297

 

6337

6810

5043

6790

0.485

0.088

0.769

1.07

0.80

1.07

738.50810

PC(34:4)

738.50832

0.298

 

1319

1640

1272

1140

0.526

0.924

0.764

1.24

0.96

0.86

772.58655

PC(36:1)

772.58727

0.932

PC(18:0/18:1)

66545

46645

51151

60081

0.010

0.030

0.379

0.70

0.77

0.90

770.57090

PC(36:2)

770.57077

-0.169

PC(18:1/18:1)

187167

121731

133430

187558

0.003

0.007

0.984

0.65

0.71

1.00

768.55541

PC(36:3)

768.55573

0.416

 

31538

22481

23141

31986

0.004

0.003

0.825

0.71

0.73

1.01

766.53981

PC(36:4)

766.53981

0.000

PC(16:0/20:4)

21857

23531

21525

22330

0.206

0.805

0.789

1.08

0.98

1.02

764.52418

PC(36:5)

764.52402

-0.209

 

5516

3833

4356

5458

0.050

0.149

0.937

0.69

0.79

0.99

762.50858

PC(36:6)

762.50820

-0.498

 

588

411

366

519

0.447

0.381

0.803

0.70

0.62

0.88

800.61789

PC(38:1)

800.61865

0.949

 

1065

585

746

1237

0.043

0.184

0.311

0.55

0.70

1.16

792.55546

PC(38:5)

792.55627

1.022

PC(16:0/22:5) PC(18:1/20:4) PC(18:0/20:5)

17092

16409

16535

16866

0.640

0.687

0.884

0.96

0.97

0.99

790.53990

PC(38:6)

790.54032

0.531

 

14255

14418

14288

13373

0.870

0.958

0.404

1.01

1.00

0.94

788.52422

PC(38:7)

788.52460

0.482

 

1535

1754

1256

1040

0.616

0.417

0.166

1.14

0.82

0.68

828.64934

PC(40:1)

828.64854

-0.965

 

263

242

125

56

0.885

0.365

0.150

0.92

0.48

0.21

826.63372

PC(40:2)

826.63287

-1.028

 

839

404

481

566

0.134

0.222

0.360

0.48

0.57

0.67

824.61821

PC(40:3)

824.61791

-0.364

 

662

648

440

812

0.945

0.238

0.597

0.98

0.66

1.23

822.60245

PC(40:4)

822.60256

0.134

 

1601

1742

1476

1822

0.461

0.514

0.414

1.09

0.92

1.14

820.58677

PC(40:5)

820.58670

-0.085

 

3034

3101

3230

3008

0.804

0.449

0.928

1.02

1.06

0.99

818.57114

PC(40:6)

818.57035

-0.965

 

4621

5790

5165

4928

0.062

0.327

0.640

1.25

1.12

1.07

816.55543

PC(40:7)

816.55428

-1.408

 

4030

4351

4269

3594

0.388

0.517

0.259

1.08

1.06

0.89

814.53985

PC(40:8)

814.53876

-1.338

 

344

457

508

646

0.313

0.327

0.243

1.33

1.48

1.88

856.67992

PC(42:1)

856.67959

-0.385

 

690

269

346

783

0.011

0.052

0.447

0.39

0.50

1.13

854.66427

PC(42:2)

854.66368

-0.690

 

788

503

371

955

0.021

0.001

0.207

0.64

0.47

1.21

852.64862

PC(42:3)

852.64860

-0.023

 

223

247

113

278

0.730

0.088

0.486

1.11

0.51

1.25

850.63301

PC(42:4)

850.63309

0.094

 

221

308

212

282

0.102

0.823

0.148

1.39

0.96

1.28

848.61726

PC(42:5)

848.61756

0.354

 

319

359

276

269

0.484

0.420

0.546

1.12

0.87

0.84

846.60161

PC(42:6)

846.60226

0.768

 

340

413

422

363

0.267

0.420

0.782

1.22

1.24

1.07

844.58594

PC(42:7)

844.58618

0.284

 

393

489

371

362

0.122

0.785

0.770

1.24

0.94

0.92

842.57047

PC(42:8)

842.57078

0.368

 

119

170

182

75

0.504

0.451

0.576

1.44

1.54

0.63

840.55468

PC(42:9)

840.55458

-0.119

 

27

117

75

42

0.165

0.417

0.664

4.32

2.78

1.54

838.54000

PC(42:10)

838.53816

-2.194

 

0

90

52

0

0.026

0.184

n/a

Inf

Inf

Inf

866.57056

PC(44:10)

866.57102

0.531

 

0

39

115

75

0.074

0.080

0.137

Inf

Inf

Inf

Figure S2: Identification of compounds discussed in the lipidomics results sections (see attached pdf). Identification of phospholipids and glycerol 3-phosphate using collision induced dissociation (CID) fragmentation.

Figure S3A: The absolute mass spectral intensities of 13C labelled phosphatidylcholine (PC) species in HL60 cells after BaP treatment in the presence of 1-13C D-glucose. This is related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section. These indicate species that had been synthesised de novo from 13C-glucose.

*

*

**

**

**

**

**

*

*

*

*

*

* p<0.05 ** p<0.005 *** p<0.0005

Figure S3B: The absolute mass spectral intensities of 12C phosphatidylcholine (PC) species in HL60 cells after BaP treatment in the presence of 1-13C D-glucose. This is related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section. These indicate species that had not been synthesised de novo from 13C-glucose and are potentially obtained exogenously.

*

**

*

*

*

*

*

**

**

***

***

***

**

*

***

***

***

***

*

* p<0.05 ** p<0.005 *** p<0.0005

Figure S4: Heatmaps showing the fold changes of individual phosphatidylcholine (PC) species in HL60 cells after BaP treatment in the presence of 1-13C D-glucose. This is related to the “BaP treatment decreases fatty acid and phospholipid synthesis and increases triacylglycerol levels” results section. (A) Changes to the levels of 13C PC species after BaP treatment (species synthesised de novo from glucose, same data as in Figure S3A). (B) Changes to the levels of 12C PC species after BaP treatment (species NOT synthesised de novo from glucose, same data as in Figure S3B).

(A)

Number of carbons

30

 

 

 

2-fold

32

*

*

**

 

1.5-fold

34

 

**

**

 

 

 

1.05-fold

36

 

*

**

**

 

*

 

 

no change

38

 

*

 

 

 

 

0.95-fold

40

 

 

 

 

 

 

 

 

 

 

0.67-fold

42

 

*

*

 

 

 

 

 

 

 

*

 

0.5-fold

44

 

 

 

 

 

 

 

 

 

 

 

0

1

2

3

4

5

6

7

8

9

10

Number of double bonds

*p<0.05 **p<0.005 ***p<0.0005

(B)

Number of carbons

30

*

**

32

 

*

*

34

 

 

*

*

 

36

 

 

 

 

*

 

 

38

 

 

**

**

***

40

 

 

 

 

 

*

**

***

***

42

 

 

 

 

 

 

 

*

***

***

***

44

 

 

 

 

 

 

 

 

 

 

***

0

1

2

3

4

5

6

7

8

9

10

Number of double bonds

Figure S5A: The absolute mass spectral intensities of 13C labelled free fatty acids in HL60 cells after BaP treatment in the presence of 13C D-glucose. This is related to the “A commercial SCD1 inhibitor can partially recapitulate the effect of BaP on lipogenesis” section. This indicates fatty acids that have been synthesised de novo from 13C-glucose.

Figure S5B: The absolute mass spectral intensities of 13C labelled saturated (SFA: C16:0 and C18:0) and monounsaturated (MUFA: C16:1 and C18:1) free fatty acids in HL60 cells after BaP treatment in the presence of 13C D-glucose. This is related to the “A commercial SCD1 inhibitor can partially recapitulate the effect of BaP on lipogenesis” section. This indicates fatty acids that have been synthesised de novo from 13C-glucose.

* p<0.05 ** p<0.005 *** p<0.0005

*

**

**

ns

* p<0.05 ** p<0.005 *** p<0.0005

***

Figure S6A: The absolute mass spectral intensities of 13C labelled phosphatidylcholine (PC) in HL60 cells after BaP treatment in the presence of 13C D-glucose. This is related to the “A commercial SCD1 inhibitor can partially recapitulate the effect of BaP on lipogenesis” section. These indicate species that have been synthesised de novo from 13C-glucose.

**

***

* p<0.05 ** p<0.005 *** p<0.0005

Figure S6B: The absolute mass spectral intensities of 12C labelled phosphatidylcholine (PC) in HL60 cells after BaP treatment in the presence of 13C D-glucose. This is related to the “A commercial SCD1 inhibitor can partially recapitulate the effect of BaP on lipogenesis” section. These indicate species that had not been synthesised de novo from 13C-glucose and are potentially obtained exogenously.

**

* p<0.05 ** p<0.005 *** p<0.0005

Figure S7: Images of cells supplemented with oleic acid related to the “Oleate decreases the levels of BaP-induced reactive oxygen species (ROS)” results section. Images of BL31 and HL60 cells stained with Jenna Giemsa after treatment with vehicle control or BaP for 24 h, with or without 300 µM oleic acid. Oleic acid induced the presence of lipid droplets in the cytoplasm in the cells.

Supplemental Reference

Southam, A. D., et al. (2007). "Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry-based metabolomics increased by the spectral stitching method." Analytical Chemistry 79(12): 4595-4602.

Control535.79664749946051433.87764588115488412.545360324337035767.63319253914411001.15128516325038518.81069417573784401.4544861980175189.06879628110397206.777736785599733155.674188539814211234.0261886958511933.4914778836842749.36263544137819521.69836463339709280.26857558414849105.094170509419712097.3010100502521070.6763673403516290.80379053752011156.0047494305166215.23062258584764158.26534996031586263.42342487583335460.37690193415239704.12488440233096579.0545896266736572.77305082977493152.587382704119371058.3823336616716829.96692028423220638.58610282856015835.48500147037670271.90383867802356177.71333324001086961.24453813375186723.7087686310093728.636487292937261535.79664749946051433.87764588115488412.545360324337035767.63319253914411001.15128516325038518.81069417573784401.4544861980175189.06879628110397206.777736785599733155.674188539814211234.0261886958511933.4914778836842749.36263544137819521.69836463339709280.26857558414849105.094170509419712097.3010100502521070.6763673403516290.80379053752011156.0047494305166215.23062258584764158.26534996031586263.42342487583335460.37690193415239704.12488440233096579.0545896266736572.77305082977493152.587382704119371058.3823336616716829.96692028423220638.58610282856015835.48500147037670271.90383867802356177.71333324001086961.24453813375186723.7087686310093728.636487292937261PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(32:2)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(36:6)PC(38:1)PC(38:5)PC(38:6)PC(38:7)PC(40:1)PC(40:2)PC(40:3)PC(40:4)PC(40:5)PC(40:6)PC(40:7)PC(40:8)PC(42:1)PC(42:10)PC(42:2)PC(42:3)PC(42:4)PC(42:5)PC(42:6)PC(42:7)PC(42:8)PC(42:9)PC(44:10)9159.36143499676848231.82453437742889924.8551311874762120876.5514674215515754.702902665907245189.61926916952119191.213074691368082.81401118398572742.281339225946343647.171840772462186839.6492865652536355.48543551533730616.5981528651216896.2530204437453854.635657555122291377.242802163474831854.28313266683819745.0894320445622306.3325578308677303.18382275008923741.550793098553981004.39847191965622826.2719634613247051.591969241978414509.4917128990569987.7978684438149994.33911293087772752.073980515208860704.39405266206381317.65892068499898441.5757481707443453.00137691450709842.92964534226417695.18570331860928613.89989158733101752.4375814235495533.06656729444525BaP427.14733802584709243.45043194768178941.4380413034727968.0969711232628641.081191248878447145.60337413931943654.5235982174636209.44158212856209165.479183559053891987.88437126509035981.9291778127508454.030741023252692082.361817446445847.65484376211464251.9446552329223450.8491431002462091349.09182505421221315.2087406224894226.34139164882168118.3669542472390571.05821598059000653.983463427499359163.24752261975544339.98463773429103716.50398321129217541.95584492070668208.6914621125087684.9293896412059357.75676648371592160.20033514833719624.04582428708197716.33388412700283320.45181260853939568.23417661800115846.09538752755415933.58062161677570982.10384477584469228.224068147339747427.14733802584709243.45043194768178941.4380413034727968.0969711232628641.081191248878447145.60337413931943654.5235982174636209.44158212856209165.479183559053891987.88437126509035981.9291778127508454.030741023252692082.361817446445847.65484376211464251.9446552329223450.8491431002462091349.09182505421221315.2087406224894226.34139164882168118.3669542472390571.05821598059000653.983463427499359163.24752261975544339.98463773429103716.50398321129217541.95584492070668208.6914621125087684.9293896412059357.75676648371592160.20033514833719624.04582428708197716.33388412700283320.45181260853939568.23417661800115846.09538752755415933.58062161677570982.10384477584469228.224068147339747PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(32:2)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(36:6)PC(38:1)PC(38:5)PC(38:6)PC(38:7)PC(40:1)PC(40:2)PC(40:3)PC(40:4)PC(40:5)PC(40:6)PC(40:7)PC(40:8)PC(42:1)PC(42:10)PC(42:2)PC(42:3)PC(42:4)PC(42:5)PC(42:6)PC(42:7)PC(42:8)PC(42:9)PC(44:10)11920.84942343043310938.71916035668311998.185466959267157132.25951130120411.152244416953271508.26642550423137464.183776441239387.74451517615313462.189657930635847688.693762650088184321.6054966449239040.28715063168839023.0628863482498995.85386794842821890.30511010342321323.214021483934647667.25651517058630851.2569206793235307.0513923932476409.53199281152968972.567811356160751246.55080351415813148.72840074170619266.626670927194921842.28805929007619572.9511860502463269.8708508137215807.973320235063281357.9429760879589718.88042457214431291.35992858492386379.50290740480472506.83868801201277826.079699579767181014.5983053447061248.40330249535242229.8578868941086454.62921536342276

Phosphatidylcholine species

Mass spectral absolute inetensity

Control2.45494619492979732.6250442898842373.97352876770526293.41126054886539442.45494619492979732.6250442898842373.97352876770526293.411260548865394416:016:118:018:1100100.0000000000000110099.99999999999998610 nM SCD1 inhibitor (ab142089)1.07891675683850562.06757573865799544.71300769121002722.07442250085451851.07891675683850562.06757573865799544.71300769121002722.074422500854518516:016:118:018:194.62515370080846883.167974422370747120.1513705065820370.058099599362436

Free fatty acid

Mass spectral intensity relative to control (%)

Control3.00681980192148132.85218271095104563.00681980192148132.8521827109510456SFAMUFA10010010 nM SCD1 inhibitor (ab142089)3.02924240168704181.72615783980105153.02924240168704181.7261578398010515SFAMUFA111.1054357327523773.109874693253559

Mass spectral intensity relative to control (%)

Control2661.20111602704365803.10080934616053266.350229377809739346.41459326766235336.96802463017215153.3704404774916532.39778902742735846.61073391518499255.935510154740828762.4156908388654380.64348331068055519.81875929110452284.0957709872105477.05787155176318507.769326202633011200.98196801243221PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(38:5)PC(40:5)PC(40:6)85554.92774446314448025.61796988797137703.96565447071695177.77414314123994045.36408038938269184.16623180866132833.68512928596133913.15045391582184545.54857970291761879.58507084893164797.3149804637769952.30577217464518688.52234607649765118.5672546450818480.544320009361422674.15224765730810 nM SCD1 inhibitor (ab14209)7861.30010116062395397.56148627949912401.199742454600740244.94342851240132852.76244808810610514.1541603982558861.708168598062910001.24845603413111896.53762600630619463.9837038524097990.49599075240717591.27763794660222256.55172085805131890.447215165485577.580211566612323527.75252175450491PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(38:5)PC(40:5)PC(40:6)81853.23767205064455741.64196804023241280.60677141638685439.02399697225898618.4835247274256620.45413330966125970.26155891818141906.02748828751252703.7308627826584932.88353605405157052.6215296190963811.37432933656221129.25459547547554963.9840989525557676.557526719790128517.698562515572

Phosphatidylcholine species

Mass spectral absolute intensity

Control1899.12572204448321435.4509406545893222.236035981461120597.96403869051917605.34771538843114029.7960398998098517.276885804603816160.0659701814896625.690773754241522153.4439689633154694.79963092560234399.17258074016174170.4495715522085062.87473961551861124.12536618347463184.14686452742491899.12572204448321435.4509406545893222.236035981461120597.96403869051917605.34771538843114029.7960398998098517.276885804603816160.0659701814896625.690773754241522153.4439689633154694.79963092560234399.17258074016174170.4495715522085062.87473961551861124.12536618347463184.1468645274249PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(38:5)PC(40:5)PC(40:6)48444.56198962734241780.11947206762931873.254712910159469278.22385375132508702.8073848472268491.74847171351150844.09234585299234863.61329433304112841.44147493926557884.12416732416138227.44125952947102809.8590304310877632.01070476445692883.55662007360726411.44279373282653335.19314914242610 nM SCD1 inhibitor (ab14209)2308.53914355846521700.6561610770883433.092363813531831323.74981867402323607.1161809817612860.76830845343611786.7746062172721796.3811703048016056.312244445876821129.6601947892966166.58050634546185517.63059855246413154.90258946188315011.15468833455721718.75427881288242524.16632128394441PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(38:5)PC(40:5)PC(40:6)38476.99235928623250723.77620681014431325.930000035361472241.65495620097516663.65098404395281067.6633515025136910.24893993777220662.0802438129151811.89627265345591317.63420783833142085.3187592454299030.40173345082465278.26329756925483159.91739753735628311.25417721999547554.797045996107

Phosphatidylcholine species

Mass spectral absolute inetnsity

Control1041.3578986501016540.455737841321591711.66363756743365859.8199330595744805.0489725621060921835.5060252724625072.4644677679225434.02941922394359374.787633384686444297.818448383251111164.2817253949161301.182776824583907.47581417220738551.11817652215018173.73539626252651123.894476756714971088.3060469561829509.69548474109388224.9956907298324397.070141085510883210.02672067779949141.62278868401836103.04710359869078176.09338177021539381.13296028881388188.9395828604649245.3275534053827379.988009219641498048.38353596210675532.99161174588201824.93446265414661422.03011967788340247.09661778230901141.25378585829894751.86640682506499923.42034901180183901041.3578986501016540.455737841321591711.66363756743365859.8199330595744805.0489725621060921835.5060252724625072.4644677679225434.02941922394359374.787633384686444297.818448383251111164.2817253949161301.182776824583907.47581417220738551.11817652215018173.73539626252651123.894476756714971088.3060469561829509.69548474109388224.9956907298324397.070141085510883210.02672067779949141.62278868401836103.04710359869078176.09338177021539381.13296028881388188.9395828604649245.3275534053827379.988009219641498048.38353596210675532.99161174588201824.93446265414661422.03011967788340247.09661778230901141.25378585829894751.86640682506499923.4203490118018390PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(32:2)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(36:6)PC(38:1)PC(38:5)PC(38:6)PC(38:7)PC(40:1)PC(40:2)PC(40:3)PC(40:4)PC(40:5)PC(40:6)PC(40:7)PC(40:8)PC(42:1)PC(42:10)PC(42:2)PC(42:3)PC(42:4)PC(42:5)PC(42:6)PC(42:7)PC(42:8)PC(42:9)PC(44:10)46911.70176868954119208.91103187733838988.29795904112201234.168465003920563.506605268914491054.18997402472139664.887402162256337.11068337834151319.421703842141166545.097957882157187166.8457810741431537.94134913852421857.2815365153265515.989383782141588.270593701376241064.669709807200217091.57966789864414255.1627614307871534.9050421812738263.09742797302926839.21345884470145662.195101362965031600.52461968371133034.14873886496754620.86637232517664029.557305542246343.65168163687781690.495502899473880787.65459221225467222.78528988167017221.03935661516232318.78823099919379339.75624501837751393.46939708192622118.5431811424471127.0434896129575580BaP798.58419615297271531.476282041790911265.7438102507469620.6416526786124791.6203442129267413532.8955717716293575.2857758961263337.98000719784022172.409409493441191761.77370948334264710.0466849005371178.2255735839315472.82463768061433224.9030804536868473.117363834595977105.06691993625698509.2085106944196649.43857045371669278.087872696066270.18160242429021956.23989956248575393.425145622238915116.43055288691062137.79616134929259223.13945214487484232.2534603315565476.31434050092315162.39561893668760526.4595391675572163.43708494938008646.65035490686046430.13975540900775140.61164843822557922.33184747652149219.91386837708934435.76905919738410943.3032148859321515.559910041108415798.58419615297271531.476282041790911265.7438102507469620.6416526786124791.6203442129267413532.8955717716293575.2857758961263337.98000719784022172.409409493441191761.77370948334264710.0466849005371178.2255735839315472.82463768061433224.9030804536868473.117363834595977105.06691993625698509.2085106944196649.43857045371669278.087872696066270.18160242429021956.23989956248575393.425145622238915116.43055288691062137.79616134929259223.13945214487484232.2534603315565476.31434050092315162.39561893668760526.4595391675572163.43708494938008646.65035490686046430.13975540900775140.61164843822557922.33184747652149219.91386837708934435.76905919738410943.3032148859321515.559910041108415PC(30:0)PC(30:1)PC(32:0)PC(32:1)PC(32:2)PC(34:1)PC(34:2)PC(34:3)PC(34:4)PC(36:1)PC(36:2)PC(36:3)PC(36:4)PC(36:5)PC(36:6)PC(38:1)PC(38:5)PC(38:6)PC(38:7)PC(40:1)PC(40:2)PC(40:3)PC(40:4)PC(40:5)PC(40:6)PC(40:7)PC(40:8)PC(42:1)PC(42:10)PC(42:2)PC(42:3)PC(42:4)PC(42:5)PC(42:6)PC(42:7)PC(42:8)PC(42:9)PC(44:10)44211.78411070421117945.64281689572831411.309373468255145932.8900951541713561.332274263763340625.3504090557198546.4668432368936810.09671057861031640.033999607657346645.162866878592121730.9620002797522480.8152243424723530.824981971883833.1287544390193411.10902508109547584.6677356875137516408.52447171074914418.2480109351441753.5132455022849242.21882262268937404.49740333911359648.09316646910771741.7661057954693101.10975851674995790.08202753508254351.0082124154405456.63299890700603268.7048681136723890.127595324690958502.98172422526522246.62526009291494308.22410914734513358.55302696851732413.33113022501391488.62349944115482170.20144431340483116.8962150621363538.862667507560786

Phosphatidylcholine species

Mass spectral absolute intensity