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Biofiles Volume 5, Number 7

Lipid Biofilesonline Biofilescontents Your gateway to Biochemicals and Reagents for Science Research Introduction 3

Biofi les Online allows you to: Natural Abundance 4 • Easily navigate the content of the Biofi les issue • Access any issue of Biofi les Isotopically Labeled Metabolites 21 • Subscribe for email notifi cations of future eBiofi les issues Characteristic Metabolites for 25 Register today for upcoming issues and Inborn Errors of eBiofi les announcements at sigma.com/biofi les Lipid Metabolites as Biomarkers for 26 the Diff erentiation of Diseased and Coming Next Issue: Based Assay Healthy Cells

Life scientists have long realized the value in analyzing Altered Lipid Metabolites in Aging 28 biological processes based on its most fundamental unit the cell. This issue will touch on a wide variety of topics ranging from ADMEtox to stem cell analysis to the most basic Lipid Metabolites in Natural 29 methods of analyzing and staining cells. The issue will announce the addition of 1400 more ECACC cell lines available in the US, Canada and Mexico. Cover: XXX

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Introduction

Roland Wohlgemuth Senior Product Specialist [email protected]

After sequencing the human genome, life metabolites has been linked to disorders scientists are now in the era “beyond the of aging like osteoporosis and vascular genome” and confronting the challenges calcification. Additionally, research is now of bringing this information to life. For lipid trying to explain how dysregulations in lipid researchers, unraveling the complexities metabolism may underlie diseases such of lipid metabolism will bring answers and as Alzheimer’s, , and asthma. Lipid opportunities in fields as diverse as medicine synthesis pathways, such as the methyl-D- and biofuels. Today, lipid research addresses 4- (MEP) pathway of all aspects of cell including cell isoprenoid synthesis, are being investigated structure, storage and generation, as potential targets for antibacterial therapies and . The synergies between and targets. As changes in lipid profiles classical lipid research, , can mark developmental stages or more and the advancement of lipid detection ominously, pathological states, there is great technologies have led to a revolution in lipid potential for the use of as biomarkers. biology and the emergence of lipidomics as Experimental quantification of the levels a branch of . of lipids and lipid metabolites is therefore Lipid-based diseases are a growing essential for enhancing the understanding and expensive challenge to health care of different influences such as genetic, systems. As a population ages, chronic nutritional, behavioral, and environmental conditions associated with aging such as factors. As part of our committment to cardiovascular disease, neurodegenerative metabolomics research, Sigma offers disorders, and metabolic disorders take an expanding range of lipids and lipid increasing tolls in terms of morbidity and metabolites for the mapping and study of mortality. Oxidation of lipids and lipid healthy and diseased cells.

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Natural Abundance Lipid Metabolites

Natural Abundance Lipid Metabolites

Glycerolipid Metabolism Name Structure . No. 1-Deoxy-D -xylulose-5- O OH O 13368-1MG O HO P O + phosphate salt CH3 • xNa 13368-5MG OH OH O CH2(CH2)6CH3 OH O 1,3-Dihydroxyacetone O D107204-5G OH dimer HO D107204-100G O CH2(CH2)6CH3 HO O D107204-500G Dihydroxyacetone O O D7137-5MG HO O P OLi O CH2(CH2)6CH3 phosphate dilithium salt D7137-10MG OLi D7137-25MG O D7137-100MG D7137-250MG

Glycerol esterified with one, two, or three fatty acids make up O O 1,2-Dimyristoyl- sn -glycero- O- Na+ P3650-25MG P 3-phosphate monosodium H C(H C) O O P3650-50MG monoacyl-, diacyl- and triacylglycerols, with a chiral center at 3 2 12 O- Na+ salt -2 of the moiety. and from and animals O O P3650-250MG are triacylglycerols, while diacylglycerols are intermediates and (CH2)12CH3 cellular messengers, and monoacylglycerols, formed by , are 1,2-Dioctanoyl- sn -glycerol - P3591-50MG 3-phosphate sodium salt and intermediates. Because triacylglycerols are insoluble 1,2-Dipalmitoyl- sn -glycerol O D9135-25MG in , combination or emulsification with other lipids, cellular H3C(H2C)14 O OH D9135-100MG compounds, or is required before transport and metabolism O O can occur. Complete or partial -catalyzed hydrolysis yields (CH2)14CH3 monoacylglycerols, glycerol, and fatty acids that can be transported 1,2-Dipalmitoyl- sn -glycero- O P4013-25MG 3-phosphate sodium salt H3C(H2C)14 O P4013-100MG and utilized for energy production or biosynthetic pathways of H3C(H2C)14 O H metabolism. O O O PO- Na+ Biosynthesis of triacylglycerols is achieved in a three-step sequence OH from 2-monoacylglycerols and fatty acids. First, the is D -(+)-, O 49800-1G viscous 49800-5G activated by acyl-CoA synthetase catalyzed conversion to the HO H OH corresponding fatty acyl thioester with . The fatty acyl- D -Glyceric acid salt O 367494-1G CoA is then coupled with a 2-monoacylglycerol by the catalytic 2+ • 2H O dihydrate HO O Ca 2 367494-5G OH action of a monoacylglycerol transferase to yield a diacylglycerol. The 2 final triacylglycerol is obtained by coupling of fatty acyl-CoA with Glycerol, anhydrous OH 49767-100ML diacylglycerol through the action of diacylglycerol transferase. HO OH 49767-250ML 49767-1L Name Structure Cat. No. rac -Glycerol 1-myristate O M1890-100MG M1890-1G O A6625-10MG CH3(CH2)11CH2 O OH CH3 OH H3C O N CH3 A6625-25G O Cl CH3 A6625-100G rac -Glycerol 1-phosphate G2138-10MG HO O P ONa A6625-500G disodium salt hexahydrate G2138-5G OH ONa • 6H O G2138-25G chloride CH3 C7017-10MG 2 Cl G2138-100G HO NCH3 C7017-5G CH3 G2138-500G C7017-25G C7017-100G sn -Glycerol 3-phosphate O G7886-250MG bis(cyclohexylammonium) HO O P OH NH2 CH G7886-1G Choline chloride 3 26978-25G OH OH Cl salt G7886-5G HO NCH3 26978-100G 2 CH3 5

O ATP AMP + PPi O Caption Text?

R OH 1 R1 S-CoA Fatty Acid Fatty Acyl-CoA HS-CoA HO CH2 O

HC O

R2 HO CH2

HS-CoA O O

O CH2 O O CH2 O R1 R1 HC O HC O

R2 R3 R2 HO CH2 O CH2 O HS-CoA O

Diacylglycerol Triacylglycerol R3 S-CoA

Name Structure Cat. No. Name Structure Cat. No. Glyceryl 1,3-dipalmitate O O D1639-1G Glyceryl trimyristate O O T5141-1G

H3C(H2C)14 O O (CH2)14CH3 CH3(CH2)11CH2 O O CH2(CH2)11CH3 T5141-5G OH CH3(CH2)11CH2 O Glyceryl 1,3-distearate - D8269-10MG O D8269-100MG Glyceryl triacetate O O T5376-500ML Glyceryl trinonadecanoate - T4632-100MG

H3C O O CH3 T5376-1L T4632-1G O CH3 Glyceryl trioctanoate O O T9126-100ML O CH3(CH2)5CH2 O O CH2(CH2)5CH3 T9126-500ML Glyceryl tributyrate O O T8626-25ML CH3(CH2)5CH2 O T9126-1L

H3C O O CH3 T8626-100ML O H C O 3 Glyceryl trioleate O T7140-500MG O O CH2(CH2)6CH3 T7140-1G O Glyceryl tridecanoate CH2(CH2)7CH3 T7517-1G T7140-5G O T7517-5G O CH2(CH2)6CH3 T7140-10G O CH2 CH O T7140-50G O CH2(CH2)6CH3 O CH2 CH2(CH2)7CH3 O O O CH2(CH2)7CH3 Glyceryl trioleate O 92860-5ML Glyceryl tridodecanoate O O T4891-100MG O CH2(CH2)6CH3 92860-10ML O CH3(CH2)9CH2 O O CH2(CH2)9CH3 T4891-5G

CH3(CH2)9CH2 O O CH2(CH2)6CH3 O O CH2(CH2)6CH3 O Glyceryl trielaidate - T7379-1G O Glyceryl triheptadecanoate - T2151-100MG Glyceryl tripalmitate T5888-100MG CH (CH ) CH T5888-500MG T2151-1G O 2 2 13 3 CH3(CH2)13CH2 O O CH2(CH2)13CH3 T5888-1G Glyceryl trilinoleate O T9517-50MG O O T5888-5G O CH O 3 T9517-100MG

O CH3 T9517-500MG T9517-1G Glyceryl tripalmitelaidate - T5909-5MG O CH3

O T9517-5G Glyceryl tripalmitoleate - T2630-100MG T2630-1G Glyceryl trilinolenate O T6513-100MG Glyceryl tristearate O O T5016-5G CH O 3 CH (CH ) CH O O CH (CH ) CH T5016-25G O 3 2 15 2 2 2 15 3 CH CH (CH ) CH O O 3 3 2 15 2 O O CH3 O Glyceryl tritricosanoate - T1412-25MG 6

Name Structure Cat. No. Name Structure Cat. No. Glyceryl tritridecanoate - T3882-500MG O -Phosphorylethanol- O P0503-10MG NH2 T3882-1G amine HO P O P0503-1G OH Glyceryl triundecanoate O O T5534-1G P0503-5G P0503-25G CH3(CH2)8CH2 O O CH2(CH2)8CH3 CH3(CH2)8CH2 O P0503-100G O P0503-500G OH 1-Lauroyl- rac -glycerol O M1765-100MG 1,2-Propanediol 12279-1ML-F OH H3C 12279-5ML-F CH3(CH2)9CH2 O OH M1765-500MG OH M1765-1G 1,3-Propanediol HO OH 81780-500ML M1765-5G 1-Propanol H3C 96566-5ML-F OH 1-Linoleoyl- rac -glycerol O M7640-100MG 96566-10ML-F H3C CH2(CH2)5CH2 O OH M7640-1G OH Propionaldehyde O 538124-250ML H C 3 H 538124-1L Lipoteichoic acid from - L3265-5MG 1-Stearoyl- rac -glycerol O M2015-100MG

Bacillus subtilis L3265-25MG CH3(CH2)15CH2 O OH M2015-1G Lipoteichoic acid from - L2515-5MG OH M2015-5G Staphylococcus aureus L2515-10MG Tripentadecanoin - T4257-100MG L2515-25MG T4257-500MG Lipoteichoic acid from - L4015-5MG T4257-1G Streptococcus faecalis L4015-25MG Tripetroselaidin - T5784-25MG Lipoteichoic acid from - L3140-5MG T5784-100MG Streptococcus pyogenes L3140-10MG L3140-25MG 1-Monopalmitoleoyl- rac - - M7890-100MG Metabolism glycerol M7890-1G

O O O 1-Oleoyl- rac -glycerol M7765-25MG O P NH2 CH (CH ) CH CH2(CH2)5CH2 O OH H C(H C) O O 3 2 6 2 M7765-50MG 3 2 14 OH OH M7765-100MG O O

M7765-1G (CH2)14CH3

O Oleoyl- L -α- CH3 L7260-1MG CH OC lysophosphatidic acid 2 Glycerol is the backbone of the fundamental used HO C H L7260-5MG sodium salt O as the self-assembling units of lipid membranes. It is interesting CH2 OPOH x Na L7260-25MG OH that both enantiomeric glycerol configurations appear in . In

O and eubacteria, are based on the Oleoyl- L -α- CH3 75347 CH OC lysophosphatidic acid 2 HO C H sn -3 configuration of the glycerol backbone, while archaebacteria sodium salt O x Na CH2 OPOH lipids are based on the sn -1-configuration. The metabolic OH intermediate for all glycerophospholipids is DL -α-Palmitin O M1640-100MG (1,2-diacylglycerol-3-phosphate). Lysophosphatidic acid, which lacks M1640-1G CH3(CH2)13CH2 O OH the acyl chain in the 2-position, is an important cellular messenger. OH 3-Palmitoyl- sn -glycerol O 76184-250MG Phosphatidylcholine () is the most abundant

H3C(H2C)14 O OH 76184-1G in animal and tissues. Phosphatidylethanolamine (cephalin) HO H is an abundant phospholipid in microbial, plant, and animal cells. 3-sn -Phosphatidic acid O P9511-5MG sodium salt from egg yolk HO O P ONa P9511-10MG The corresponding lysophosphatidic acid derivatives, lysophos- OH ONa lecithin P9511-50MG phatidylcholine and lysophosphatidylethanolamine, are more soluble P9511-100MG in water and have properties, and these are not standard P9511-500MG components of cell membranes. Phosphatidylglycerol has important Phosphocholine chloride CH3 Cl P0378-10MG O • 4H2O H C N functions in lung surfactants, , and bacterial membranes calcium salt tetrahydrate 3 O P O P0378-5G CH 2+ 3 O Ca P0378-25G and is a in the biosynthesis of cardiolipin. P0378-50G Phosphatidylserine is involved in biological processes including O O D- (−)-3-Phosphoglyceric Na+ -O P8877-10MG P apoptosis, coagulation, and activation of C. acid disodium salt O O- Na+ P8877-1G HO It can be found in plasma membranes and other membranes of OH P8877-5G animals, plants, and . Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 7

A class of phospholipids with a high rate of metabolism is the Name Structure Cat. No.

O phosphatidylinositols which have varying degrees of 1,2-Dierucoyl-sn-glycero-3- O 74576 CH (CH ) CH CH=CHCH (CH ) CH O O P O 3 2 6 2 2 2 9 2 NH in the polar head group myo-inositol. The metabolic conversion of phosphoethanolamine O O OH 2 CH2(CH2)9CH2CH=CHCH2(CH2)6CH3 phosphatidylinositols to diacylglycerols and inositol is important in the of vital cellular functions such as O 1,2-Dierucoyl- sn -glycero- O OH 00259 differentiation, proliferation, and apoptosis, and in anchoring proteins CH3(CH2)7CH CH(CH2)10CH2 O O P O OH 3-phospho-rac -(1-glycerol) O O ONa sodium salt via a glycosyl-bridge to the plasma membrane. CH3(CH2)7CH CH(CH2)10CH2

CH2OH CH2OPO3H2 Diethanolamine HOCH2CH2NHCH2CH2OH 31589-100G OH C H OH C H 31589-500G CH OH CH2OPO3H2 2 1,2-Dihexadecanoyl- rac - - P5650-100MG glycero-3-phospho-rac -(1- sn-Glycerol 3-phosphate sn-Glycerol 1-phosphate [L-(glycerol 3-phosphate) = D-(glycerol 1-phosphate)] [L-(glycerol 1-phosphate) = D-(glycerol 3-phosphate)] glycerol) salt 1,2-Dihexadecyl- rac - - P3777-25MG Name Structure Cat. No. glycero-3-phosphocholine P3777-100MG

O H C CH 1,2-Di-O-hexadecyl-sn - - P1527-100MG 2-Arachidonoyl-1- O 3 3 P1287-5MG N stearoyl-sn -glycero-3- CH3(CH2)15CH2 O O P O CH3 P1287-25MG glycero-3-phosphocholine P1527-500MG O O phosphocholine O 1,2-Dihexadecyl- O 37161-100MG O H C(H C) P NH sn -glycero-3- 3 2 15 O O 2 OH 37161-1G CH3 phosphoethanolamine O (CH2)15CH3

Cardiolipin sodium salt - C0563-10MG from bovine C0563-25MG 1,2-Dilinoleoyl- sn -glycero- P0537-5MG 3-phosphocholine C0563-100MG P0537-25MG C0563-500MG 1,2-Dimyristoyl- - C5430-5MG sn -glycerol-3-(5′- C5430-25MG Cytidine 5′-diphospho- NH2 C0256-100MG diphosphocytidine) choline sodium salt C0256-500MG O O N salt dihydrate -O P O P O C0256-1G - N O O O O 1,2-Dimyristoyl- sn - O O - + P3650-25MG (H C) +N O Na 3 3 P + glycero-3-phosphate H C(H C) O O P3650-50MG Na 3 2 12 O- Na+ OHOH monosodium salt O O P3650-250MG

(CH2)12CH3 1,2-Didecanoyl- sn -glycero- O O CH3 P7081-25MG O N+ O 3-phosphocholine P 1,2-Dimyristoyl- sn -glycero- O CH P2663-25MG H3C(H2C)8 O O – CH3 P7081-100MG 3 O H3C 3-phosphocholine CH3(CH2)11CH2 O O P O N CH3 O O P7081-1G P2663-100MG CH (CH ) CH O O CH3 3 2 11 2 P2663-500MG (CH2)8CH3 O P2663-1G O O 1,2-Didocosahexaenoyl- sn- CH3 78896-100MG H3C O O P O N+ CH O O O- 3 CH glycero-3-phosphocholine CH3 1,2-Dimyristoyl- rac - O O 3 P7930-100MG H C 78896-500MG O 3 glycero-3-phosphocholine P N+ H3C(H2C)12 O O – CH3 P7930-250MG O H3C O O

(CH2)12CH3 1,2-Didodecanoyl- sn - O O CH3 P1263-25MG O + P N 1,2-Dimyristoyl- sn -glycero- CH3 P5693-100MG glycero-3-phosphocholine CH3(CH2)9CH2 O O – CH3 P1263-100MG O H3C O O 3-phosphoethanolamine P1263-500MG P5693-250MG CH2(CH2)9CH3 P5693-1G O

O H C CH O O 1,2-Didodecanoyl- rac - O 3 3 P1534-100MG NH2 N O O P O glycero-3-phosphocholine CH (CH ) CH O O P O CH 3 2 9 2 3 OH O CH3(CH2)9CH2 O O

O

CH O 3 O CH 1,2-Dieicosapentaenoyl- H C 3 40723-100MG 3 + O O P O N CH3 - O O O CH3 O sn-glycero-3- 40723-500MG 1,2-Dimyristoyl- sn -glycero- O OH 43096-100MG H3C phosphocholine 3-phospho-rac -(1-glycerol) CH3(CH2)11CH2 O O P O OH 43096-1G ammonium salt O O O- + CH2(CH2)11CH3 NH4

O O 1,2-Dierucoyl- sn-glycero- CH 77017 CH (CH ) CH CH=CHCH (CH ) CH O O P O 3 O 3 2 6 2 2 2 9 2 N+ CH 1,2-Dimyristoyl- sn -glycero- P6412-25MG O O O- 3 O OH 3-phosphocholine CH 3 O P O CH2(CH2)9CH2CH=CHCH2(CH2)6CH3 3-phospho- rac -(1-glycerol) CH3(CH2)11CH2 O OH P6412-100MG O O ONa sodium salt P6412-500MG CH2(CH2)11CH3

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Name Structure Cat. No. Name Structure Cat. No. O - 1,2-Dimyristoyl- sn -glycero- O OH 90998-100MG 1,2-Dipalmitoyl- rac - P5911-100MG 3-phospho-rac -(1-glycerol) CH3(CH2)11CH2 O O P O OH 90998-1G glycero-3-phosphocholine P5911-250MG O O ONa sodium salt P5911-1G CH2(CH2)11CH3 2,3-Dipalmitoyl- sn -glycero- O O CH3 42566-25MG O 1-phosphocholine P N+ O H3C(H2C)14 O O – CH3 1,2-Dimyristoyl- sn-glycero- O NH 80114-100MG O H3C 2 O O 3-phospho-L - CH3(CH2)11CH2 O O P O OH 80114-500MG O O ONa (CH ) CH sodium salt O 2 14 3 CH2(CH2)11CH3 O O 1,2-Dipalmitoyl- sn -glycero- O P1348-25MG P NH O 3-phosphoethanolamine H C(H C) O O 2 P1348-100MG 1,2-Dioctadecanoyl- sn - O OH 05717-100MG 3 2 14 OH O O glycero-3-phospho-rac -(1- H3C(H2C)15H2C O O P O OH 05717-1G P1348-250MG O O O- glycerol) ammonium salt (CH2)14CH3 P1348-1G NH + CH (CH ) CH 4 2 2 15 3 O 1,2-Dipalmitoyl- O P3275-100MG NH2 CH2(CH2)6CH3 rac -glycero-3- CH3(CH2)13CH2 O O P O P3275-500MG 1,2-Dioleoyl- sn -glycero-3- O P6354-25MG O CH3 phosphoethanolamine CH (CH ) CH O OH phosphocholine P6354-100MG 3 2 13 2 CH2(CH2)5CH2 O O P O N CH3 O O O CH3 P6354-1G CH2(CH2)5CH2 O O 1,2-Dipalmitoyl- sn -glycero- O OH P9789-25MG CH2(CH2)6CH3 3-phospho- rac -(1-glycerol) CH3(CH2)13CH2 O O P O OH P9789-100MG sodium salt O O ONa RO CH CH (CH ) CH 1,2-Dioleoyl- sn -glycero-3- 2 42490-2.5ML 2 2 13 3 RO H O phosphoethanolamine NH 42490-10ML H C O P O 2 O 2 − 1,2-Dipalmitoyl- sn -glycero- 50984-100MG O O OH O 3-phospho-rac -(1-glycerol) CH3(CH2)13CH2 O O P O OH 50984-1G R : H3C(CH2)6CH2 (CH2)7 C sodium salt O O ONa CH (CH ) CH 1,2-Dioleoyl- sn -glycero-3- RO CH2 76548-100MG 2 2 13 3

RO H O phosphoethanolamine NH 76548-1G H C O P O 2 O 2 − 1,2-Dipalmitoyl- sn -glycero- O OH 42627-100MG O O 3-phospho- ra c-(1-glycerol) CH3(CH2)13CH2 O O P O OH 42627-1G R : H3C(CH2)6CH2 (CH2)7 C O O O- ammonium salt + NH4 O CH (CH ) CH 1,2-Dioleoyl- sn -glycero-3- O OH P9664-5MG 2 2 13 3 CH3(CH2)6CH2CH=CHCH2(CH2)5CH2 O O P O OH phospho- rac -(1-glycerol) O O ONa P9664-25MG O CH2(CH2)5CH2CH=CHCH2(CH2)6CH3 1,2-Dipalmitoyl- sn -glycero- P1185-10MG sodium salt P9664-100MG O 3-phospho-L -serine HO P O ONa P1185-50MG P9664-500MG O NH sodium salt O 2 O 1,2-Dioleoyl- sn -glycero-3- O OH 74384-100MG O CH2(CH2)13CH3 CH3(CH2)13CH2 O CH3(CH2)6CH2CH=CHCH2(CH2)5CH2 O O P O OH phospho-rac -(1-glycerol) O O ONa 74384-1G O sodium salt CH2(CH2)5CH2CH=CHCH2(CH2)6CH3 O 1,2-Dipalmitoyl- rac - O P1902-5MG

glycero-3-phospho- L - HO P O OH P1902-25MG O O NH 1,2-Dioleoyl- sn -glycero- O 74304-100MG serine O 2 H3C(H2C)6H2C H2C(H2C)5H2C O O P OH 3-phosphoric acid O O ONa 74304-500MG O CH2(CH2)13CH3 CH3(CH2)13CH2 O CH (CH ) CH monosodium salt 2 2 5 2 CH2(CH2)6CH3 O

1,3-Dipalmitoyl-2- O D2157-10MG CH (CH ) CH O 1,2-Dioleoyl- sn -glycero-3- - P1060-5MG oleoylglycerol 3 2 13 2 O D2157-50MG CH (CH ) CH O 3 2 13 2 CH (CH ) CH CH (CH ) CH L O 2 2 5 2 2 2 6 3 phospho- -serine sodium P1060-10MG O D2157-100MG salt P1060-25MG

1,2-Dioleoyl-3-linoleoyl- - D9925-100MG rac -glycerol 1,2-Dipalmitoylphosphati- H3C P7115-100UG dylinositol 1,2-Dioleoyl-3-palmitoyl- - D1782-10MG 4,5-diphosphate O O rac -glycerol R= P OH D1782-100MG O O OH 1,3-Dioleoyl-2- - D1657-25MG O O P OH O O palmitoylglycerol HO OR

H3C O CH OH HO 1,2-Dipalmitoyl- sn -glycero- O 3 P0763-50MG N CH CH (CH ) CH O O P O 3 3-phosphocholine 3 2 13 2 CH P0763-100MG O 3 OR CH3(CH2)13CH2 O P0763-250MG O P0763-1G P0763-5G 1,2-Dipalmitoylphosphati- O O P4240-100UG O CH CH3(CH2)13CH2 O O P OH 1,2-Dipalmitoyl- sn -glycero- O 3 P4329-25MG dylinositol CH3(CH2)13CH2 O O O O N CH3 OH CH (CH ) CH O O P O HO P O P OH • 6Na+ 3-phosphocholine 3 2 13 2 CH P4329-100MG 3,4,5-trisphosphate O O 3 HO O OH CH3(CH2)13CH2 O P4329-500MG tetrasodium salt OH O O P OH O P4329-1G OH Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 9

Name Structure Cat. No. Name Structure Cat. No. O - 1,2-Distearoyl- sn -glycero- O OH 55845-100MG L -α-Phosphatidyle- P1223-25MG 3-phospho-rac -(1-glycerol) CH3(CH2)15CH2 O O P O OH 55845-1G thanolamine, dioleoyl P1223-100MG O O ONa sodium salt P1223-500MG CH2(CH2)15CH3 O L -α-Phosphatidylinositol OH O P1368-500UG 1,2-Distearoyl- sn-glycero- O 43307-100MG dipalmitoyl ammonium HO O P O O CH2(CH2)13CH3 O NH2 salt OH O CH2(CH2)13CH3 3-phospho-L -serine CH3(CH2)15CH2 O O P O OH 43307-500MG HO OH O sodium salt O O ONa OH O CH (CH ) CH 2 2 15 3 L -α-Phosphatidyl-D -myo - CH3 P4725-.1MG Ethanolamine NH2 398136-25ML inositol 3,4-diphosphate, HO O O 398136-500ML dioctanoyl R= P OH O O OH 398136-2.5L O O P OH O - O L -α-Glycerophosphoryl- G5291-10MG HO OH choline G5291-50MG CH3 OR HO G5291-100MG

O 2-Linoleoyl-1- O 62225-25MG OR NH2 CH3(CH2)13CH2 O O P O palmitoyl-sn -glycero-3- O O OH

CH2(CH2)3CH3 phosphoethanolamine L -α-Phosphatidyl-D -myo - CH3 P3584-.1MG inositol 4,5-diphosphate, O O dioctanoyl R= P OH O O OCH3 O CH3 OH 1-O-Octadecyl-2-O- O9262-5MG O O P OH CH3(CH2)16CH2O O P O N CH3 methyl-sn -glycero-3- O O CH3 O phosphorylcholine HO OR CH3 1-Oleoyl- sn -glycero-3- O L1881-5MG OH HO O CH3 phosphocholine CH2(CH2)5CH2 O O P O N CH3 L1881-25MG OH O CH3 L1881-100MG OR CH2(CH2)6CH3

L -α-Phosphatidyl-D -myo - H3C P5713-.1MG 1-Oleoyl-2-palmitoyl- sn - - P4142-5MG inositol 3,5-diphosphate, glycero-3-phosphocholine P4142-25MG dipalmitoyl O O R= P OH P4142-100MG O O OH O O O P OH 2-Oleoyl-1-palmitoyl- sn - O P3017-10MG CH O 3 O HO glycero-3-phosphocholine CH3(CH2)13CH2 O O P O OR N+ P3017-25MG – CH3 O O O H3C CH3 P3017-100MG OR HO

CH2(CH2)6CH=CH(CH2)7CH3 OH O 2-Oleoyl-1-palmitoyl- sn - O 42773-100MG CH3 glycero-3-phosphocholine CH3(CH2)13CH2 O O P O + 42773-500MG – N CH O O O 3 CH3 L -α-Phosphatidyl- CH3 P5578-.1MG CH2(CH2)6CH=CH(CH2)7CH3 D -myo -inositol O O 3-monophosphate, R= P OH O O 2-Oleoyl-1-palmitoyl- sn- O 76559-100MG OH O OH dioctanoyl O O P OH CH (CH ) CH O O P O OH glycero-3-phospho-rac-(1- 3 2 13 2 76559-500MG O O O ONH4 O glycerol) ammonium salt HO OH CH (CH ) CH CH=CHCH (CH ) CH 2 2 5 2 2 2 6 3 CH 3 OR HO 2-Oleoyl-1-palmitoyl- sn- O 63371-100MG O OH OH glycero-3-phospho-rac-(1- CH3(CH2)13CH2 O O P O OH 63371-1G O O ONa glycerol) sodium salt CH2(CH2)5CH2CH=CHCH2(CH2)6CH3 L -α-Phosphatidyl- H3C P3953-.1MG D -myo -inositol 3-monophosphate, 2-Oleoyl-1-palmitoyl- sn- O 51581-100MG O O O NH2 R= P OH CH (CH ) CH O O P O dipalmitoyl O O glycero-3-phospho-L - 3 2 13 2 OH 51581-1G OH O O ONa O O P OH O serine sodium salt O CH2(CH2)5CH2CH=CHCH2(CH2)6CH3 O HO OH

H3C OR HO 2-Oleoyl-1-stearoyl- sn - - P9649-10MG glycero-3-phosphocholine P9649-25MG OH - 1-O-Palmityl-2- P6284-5MG palmitoyl-rac -glycero-3- phosphocholine

DL -α-Phosphatidylcholine, - P8180-100MG distearoyl P8180-500MG

L -α-Phosphatidylcholine, - P1186-1MG β-O-methyl-γ-O-octadecyl P1186-5MG 10

Name Structure Cat. No. Name Structure Cat. No.

L -α-Phosphatidyl- O P7686-.1MG β-Acetyl-γ-O-alkyl-L -α- O P7568-1MG D -myo -inositol CH (CH ) CH O O phosphatidylcholine from 3 2 13 2 O CH3 P7568-5MG CH (CH ) CH O O P OH 4-monophosphate, 3 2 13 2 bovine heart lecithin H3C(CH2)15 O P7568-10MG dipalmitoyl ammonium O O O O HO OH P salt - OH HO O O • xNH3 O

O P OH + H3C N CH3 OH CH3

L -α-Phosphatidyl-D -myo - CH3 P9953-.1MG β-Acetyl-γ-O-hexadecyl-L - O P4904-1MG inositol 3,4,5-triphosphate, O α-phosphatidylcholine O O CH3 P4904-5MG dioctanoyl R= P OH H C(CH ) O O O 3 2 15 P4904-10MG OH O O O P OH O P P4904-25MG O - O O O HO OR CH 3 OR HO + H3C N CH3 CH3 OR 1-O-Palmityl-2-acetyl-rac - - P1402-10MG 1-Stearoyl- sn -glycero-3- - L2131-5MG glycero-3-phosphocholine phosphocholine L2131-100MG 1-O-Palmityl-2-acetyl- - H8771-250UG sn -glycero-3-phospho- Triethanolamine OH 90278-100ML (N,N,N-trimethyl) N 90278-500ML HO OH hexanolamine 1-O-Palmityl-2- - P2190-5MG arachidonoyl-sn -glycero- Ether Lipid Metabolism 3-phosphocholine H C CH O 1-O-Palmityl-sn -glycero-3- O 3 3 L5016-1MG N phosphocholine CH (CH ) CH O O P O CH O CH3 3 2 14 2 3 L5016-10MG O H3C(CH2)15 O OH O O P 1-O-Palmityl-2-O- - P6034-5MG O O- methyl- rac -glycero-3- phosphocholine + H3C N CH3 CH3 Phospholipids containing an aliphatic-ether bond or vinyl- Metabolism ether bond to the carbon-1 of L -glycerol yield 1-alkylglycerols OH or 1-alkenylglycerols when hydrolyzed. Platelet-activating factor CH3(CH2)13CH2 OH (PAF; 1-alkyl-2-acetyl-sn -glycerophosphorylcholine) produces NH2 important biological effects such as the aggregation of platelets contain a lipophilic long-chain amino and induction of hypertensive response at very low . like , dihydrosphingosine, phytosphingosine, or The for alkylglycerolipids in the endoplasmatic dehydrophytosphingosine as the characteristic polyalcohol reticulum of tumors and certain healthy cells consist of alkylation constituent. Sphingosine or a related base is bound to a long-chain of dihydroxyacetone phosphate, reduction, acylation, fatty acid by an amide linkage and via the terminal hydroxyl group dephosphorylation, acylation, and/or transfer of phosphorylcholine to either a complex or -containing moiety. or phosphorylethanolamine to alkyl glycerol. Pancreatic , , , -polyhexosides, and phospholipases, and do not attack alkyl or 1-alkenyl are , i.e., contain a carbohydrate component chains of glycerolipids. Ether-linked phosphatidylcholines instead of phosphorylcholine. The carbohydrate moiety of a and phosphatidylethanolamines containing arachidonic and is oriented towards the exterior docosapentaenoic fatty acids are decreased in the blood plasma of surface and is characteristic for the cell type, species, growth phase, hypertensive individuals. and differentiated/undifferentiated status.

Name Structure Cat. No.

N-Acetyl- D -sphingosine OH A7191-1MG

HO CH2(CH2)11CH3 A7191-5MG H3C NH O Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 11

Name Structure Cat. No. Name Structure Cat. No. Asialoganglioside GM CH2OH NHR G9402-.5MG Disialoganglioside GD Gal-GalNac-Gal-Glc-Ceramide G8146-1MG 1 O O(CH2)12CH3 1b OH from bovine brain CH2OH CH2OH from bovine brain HO O OH HOCH2 O O O SA SA O OH HO O OH R = fatty acid OH NHAc OH Galactocerebrosides from R R=fatty acid C4905-10MG NH OH CH2OH bovine brain HO C4905-25MG OO (CH2)12CH3 CH2OH NHR Asialoganglioside-GM2 G9398-50UG OH O O(CH2)12CH3 OH OH from bovine brain CH2OH CH2OH G9398-.1MG OH HO O O O O OH OH OH OH R = fatty acid N-Hexanoyl- D -sphingosine OH H6524-1MG NHAc OH H6524-5MG CH3(CH2)11CH2 OH H3C NH Ceramide from bovine - 22244 O brain Lactocerebrosides from - C3166-1MG D -erythro -Ceramide C8 OH O C8355-1MG bovine brain C3166-5MG 1-phosphate CH3(CH2)11CH2 O P OH AcHN O CO2H R = fatty acid CH3(CH2)5CH2 NH OH Monosialoganglioside G OH G5642-.5MG M3 OH CH2OH NHR O from canine blood CH2OH G5642-1MG O O(CH2)12CH3 OH CH OH OH O 2 Ceramide 1-phosphate C4832-1MG OH HO O O from bovine brain C17H35 NH O O OH

CH3(CH2)12 O POH O OH OH Monosialoganglioside G - G7641-1MG Ceramide - C4987-5MG M1 from bovine brain phosphorylethanolamine G7641-5MG G7641-10MG Dihydroceramide C2 HO C7980-5MG O - Monosialoganglioside GM1 G9652-1MG CH3(CH2)13CH2 C7980-25MG N CH3 from bovine brain H OH - Monosialoganglioside GM2 G8397-1MG Dihydroceramide C6 - C8230-5MG from bovine brain C8230-25MG N-Octanoyl- D -sphingosine OH O1882-5MG Dihydroceramide C8 OH C8605-5MG HO CH2(CH2)11CH3

CH3(CH2)13CH2 OH C8605-25MG HN CH2(CH2)5CH3 HN CH2(CH2)5CH3 O O N-Palmitoyl- D - - P6778-1MG D -erythro - OH D3314-10MG P6778-10MG

Dihydrosphingosine CH3(CH2)13CH2 OH D3314-50MG semisynthetic from bovine NH2 brain sphingomyelin

H2N Phytoceramide C2 - C8105-5MG D -threo - OH D4556-1MG

Dihydrosphingosine Phytosphingosine NH2 OH • HCl P2795-5MG HO C15H31 hydrochloride HO CH2(CH2)12CH3 P2795-25MG L -threo - OH D4681-1MG OH Dihydrosphingosine CH3(CH2)13CH2 OH Psychosine from bovine NH2 P9256-1MG NH2 brain H3C(CH2)12 P9256-10MG OH DL -Dihydrosphingosine D6783-10MG OH

CH3(CH2)13CH2 OH D6783-25MG CH2OH O OH NH2 D6783-100MG O OH D OH - erythro - O D3439-1MG Dihydrosphingosine CH3(CH2)13CH2 O P OH OH 1-phosphate NH2 OH Sphingomyelin S7004-5MG AcHN O CO2H Disialoganglioside-GD OH G0776-.1MG 2 OH CH OH 2 S7004-10MG from bovine brain, CH2OH OH O S7004-50MG semisynthetic HO AcHN CO H O 2 R = fatty acid S7004-100MG CH2OH NHR S7004-500MG OH O O(CH2)12CH3 OH CH2OH CH2OH OH HO O O O O Sphingomyelin S0756-50MG OH O OH S0756-100MG NHAc OH S0756-500MG

D -Sphingosine OH S7049-5MG

H3C(H2C)12 OH S7049-25MG NH2 Disialoganglioside GD1a Gal-GalNac-Gal-Glc-Ceramide G2392-1MG from bovine brain G2392-5MG SA SA 12

Name Structure Cat. No. elongation scheme of fatty acid biosynthesis is catalyzed by either L -erythro -Sphingosine OH S7174-5MG discrete catalyzing specific steps or by a large multi- CH3(CH2)11CH2 OH complex able to catalyze all steps in the pathway. NH2 OH The first step of converting acetyl CoA into the more reactive acetyl- Sphingosine 1-phosphate O S9666-1MG CH3(CH2)11CH2 O P OH acyl carrier protein (Acetyl-ACP) is catalyzed by ACP transacylase. NH OH 2 The is then transferred from ACP to a residue Sphingosylphosphoryl- OH O O– S4257-10MG P of the synthase complex. In the third step, carboxylation of acetyl choline H3C H3C(H2C)12 O O S4257-25MG N+ CH3 NH2 CoA is catalyzed by acetyl CoA carboxylase with and CH 3 ATP to yield malonyl CoA and ADP. In this reaction, biotin acts as a Sulfatides from bovine - S1006-5MG carrier which transfers carbon dioxide to acetyl CoA. brain S1006-10MG S1006-50MG The malonyl group is subsequently converted through a nucleophilic

Trisialoganglioside-GT1b G3767-1MG acyl substitution reaction into malonyl-ACP. Thus, both acetyl and from bovine brain G3767-5MG malonyl groups are bound to an ACP arm of the synthase complex. The key fifth step consists of the Claisen condensation reaction between the bound acetyl and malonyl groups to give acetoacetyl- ACP. In the sixth step, an enantioselective reduction of the ketone

O carbonyl group catalyzed by β-ketothioester yields

H3C CH2(CH2)7CH2 OH β-hydroxybutyryl-ACP, with a new chiral center in the R -configuration. Enzymatic in step 7 yields trans -crotonyl-ACP, which is Acetyl coenzyme A is a central for both the biosynthesis converted in step 8 by NADPH-dependent reduction of the carbon- and of fatty acids. Although the steps in the biosynthetic carbon double bond to butyryl-ACP. and catabolic schemes are closely related, there are specific differences. The individual steps are also independent by their Fatty acid catabolism in the mitochondria of cells provides energy by spatial separation in biological cells, as biosynthesis occurs in the the β-oxidation pathway and is composed of a repetitive sequence while catabolism takes place in the mitochondria. The even- of four enzymatic reaction steps. The fatty acid chain is cleaved from the carboxy-terminus in a stepwise fashion. The first step of numbered ([C2 ]n ) common fatty acids result from the sequential two-carbon elongation of acetyl CoA by a series of enzymatic the β-oxidation pathway starts with an acyl CoA-- reactions utilizing one or more of acetyl CoA. The two-step catalyzed desaturation at C2-C3 using an FAD to yield an α,β-

HCO - + ATP Caption Text? HS-Acyl Carrier Protein O 3

H C S CoA HS-Coenzyme A 3 ADP + Pi Acetyl-Coenzyme A O O O Malonyl-Coenzyme A

H3C S Acyl Carrier Protein HO C S CoA H2 HS-Synthase HS-Acyl Carrier Protein

HS-Acyl Carrier Protein HS-Coenzyme A O O O Malonyl-Acyl Carrier Protein

H3C S Synthase HO C S Acyl Carrier Protein H2

O - S-Synthase O O H2 C + CO2 Acetoacetyl- H3C C S Acyl Carrier Protein H2 Acyl Carrier Protein H3C C S Acyl Carrier Protein H Butyryl Acyl Carrier Protein NADPH 2 NADP+ NADP+ OH O NADPH O trans-Crotonyl- beta-(R)-Hydroxybutyryl- Acyl Carrier Protein Acyl Carrier Protein H3C C S Acyl Carrier Protein H3C C S Acyl Carrier Protein H2 H2O H Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 13

unsaturated acyl-CoA. An enoyl-CoA hydratase-catalyzed syn- addition Name Structure Cat. No. of water to the α,β-unsaturated acyl-CoA in the second step yields Butyryl coenzyme A NH2 B1508-5MG N N O OH salt hydrate H H O O B1508-10MG 3 S -hydroxyacyl-CoA. Next, 3S -hydroxyacyl-CoA is oxidized to the N N N N H3C S O P O P O O O O H C CH3 OH OH B1508-25MG corresponding β-ketoacyl-CoA by NAD-dependent enantioselective 3 O + HO P O OH • xLi • yH2O 3-hydroxyacyl-CoA . In the final step, the β-ketoester OH is cleaved to two CoA in a β-ketoacylthiolase-catalyzed retro- Claisen reaction. While the common fatty acids with an even number Coenzyme A hydrate H C4282-10MG N SH of carbon atoms produce two molecules of acetyl-CoA in the final NH C4282-25MG O NH O 2 C4282-100MG passage, fatty acids with an odd number of carbon atoms lead to one N N O O HO of acetyl-CoA and one molecule of propionyl-CoA. O P O P O N N H3C CH3 OH OH O O Name Structure Cat. No. • xH2O HO P O OH OH Acetoacetyl coenzyme A - A1625-5MG NH2 sodium salt hydrate Coenzyme A sodium salt C3144-10MG A1625-10MG N hydrate N C3144-25MG A1625-25MG O O H3C CH3 O O HS O P O P O N N N N O C3144-100MG Acetyl coenzyme A NH2 A2056-1MG H H OH OH OH C3144-500MG N sodium salt N A2056-5MG + O OH H3C CH3 O O • xNa HO P OH C3144-1G HO O N A2056-10MG • yH2O P O P O N O O A2056-25MG OH OH O NH O A2056-100MG • xNa O OH NH Coenzyme A trilithium salt NH2 C3019-10MG HO P O H3C S N N OH C3019-25MG N O O O N C3019-100MG O O O NH HS N N P P O C3019-500MG Acetyl coenzyme A 2 A2181-1MG H O– H OH O – trilithium salt O N O O C3019-1G N A2181-5MG + + Li+ S CH Li Li O O OH H 3 N A2181-10MG P - + N – O N O Li Li+ A2181-25MG HO O CH3 O P O O- O OH H C - Li+ A2181-100MG 3 O P O O Coenzyme A, oxidized - C2643-5MG HN O O P OH OH O lithium salt C2643-10MG O Crotonoyl coenzyme A NH 28007-5MG Arachidic acid O 10930-1G 2 trilithium salt N N 28007-25MG O O CH3(CH2)17CH2 OH 10930-5G H C CH 3 3 N N 10930-25G HO O P O P O O OLi OLi O NH Arachidonic acid O 10931-250MG O OH O H3C OH P 10931-1G HO O NH OLi

Arachidonoyl coenzyme A NH2 A5837-5MG S CH lithium salt N N A5837-10MG 3 O O CH N O 3 O O N O O O HN N P P O Decanoyl coenzyme A NH2 D5269-5MG H CH3 HO OH OH monohydrate N N O OH D5269-25MG S O O O CH3 O O O P OH Li N O P O P O N O- HN N H CH OH OH O HO 3 CH3 O HO P O OH S CH2(CH2)7CH3 • H2O OH Arachidonylethanolamide O A0580-5MG O C NH CH2CH2OH A0580-25MG 3 ′-Dephosphoco enzyme A - D3385-5MG CH3 D3385-25MG O Behenic acid O 216941-5G cis -13,16-Docosadienoic D4034-25MG acid methyl H3C CH2(CH2)9CH2 OCH3 CH3(CH2)19CH2 OH O 2-Butenoyl coenzyme A - C6146-5MG cis -4,7,10,13,16,19- D2534-25MG Docosahexaenoic acid H3C OH lithium salt C6146-10MG D2534-100MG C6146-25MG D2534-1G cis -4,7,10,13,16,19- - D8768-5MG Docosahexaenoic acid D8768-25MG sodium salt 14

Name Structure Cat. No. Name Structure Cat. No.

NH2 all-cis -7,10,13,16,19- D1797-10MG Hexanoyl coenzyme A O H2012-5MG N N Docosapentaenoic acid OH trilithium salt hydrate HN O H C CH O O 3 3 N H2012-10MG CH (CH ) CH S O P O P O N 3 2 3 2 N CH O H OLi OLi O 3 O OH O • xH2O LiO P O OH OH cis -11,14-Eicosadienoic O E3127-25MG acid OH E3127-100MG H3C CH2(CH2)7CH2 OH O cis -11,14-Eicosadienoic O E7752-25MG (R )-3-Hydroxybutyric acid 54920 H C OH acid ethyl ester H3C CH2(CH2)7CH2 O CH3 3

DL -β-Hydroxybutyryl - H0261-10MG cis -11,14-Eicosadienoic - E7877-25MG coenzyme A lithium salt H0261-25MG acid methyl ester E7877-100MG DL -3-Hydroxy-3- NH2 H6132-5MG cis -5,8,11,14,17- H3C E2011-10MG methylglutaryl N N H6132-10MG O E2011-25MG O O O coenzyme A sodium salt H3C CH3 O P O P O N N • xNa H6132-25MG OH E2011-50MG HN O OH OH OH E2011-100MG • 3H2O O O OH cis -5,8,11,14,17- COOH E6627-5MG O N P OH H Eicosapentaenoic acid E6627-10MG S OH OH sodium salt E6627-25MG O HO CH3O

Isobutyryl coenzyme A - I0383-5MG cis -5,8,11-Eicosatrienoic - E5888-1MG lithium salt I0383-10MG acid E5888-10MG cis -8,11,14-Eicosatrienoic H H E4504-10MG Isovaleryl coenzyme A CH3 NH2 I9381-10MG H H acid E4504-100MG lithium salt hydrate H3C O N • yH O N O 2 H S N H N - + + CH3 H OH O N O Li Li CH3 O P O O- O OH + - H3C - Li cis -5,8,11-Eicosatrienoic E6013-1MG O P O O acid methyl ester HN O O P OH OH O cis -8,11,14-Eicosatrienoic O E3511-50MG O H3C acid methyl ester OCH3 Lauroyl coenzyme A - L2659-5MG cis -11,14,17-Eicosatrienoic - E6001-100MG lithium salt L2659-25MG acid methyl ester O cis -11-Eicosenoic acid E3635-100MG Lignoceric acid L6641-100MG CH3(CH2)7 (CH2)9COOH L6641-1G E3635-1G CH3(CH2)21CH2 OH L6641-5G Elaidic acid O E4637-1G L6641-10G H3C(H2C)7 OH E4637-5G O E4637-25G Linoleic acid L1376-10MG CH3(CH2)3CH2 OH L1376-500MG Elaidic acid O 45090-10G L1376-1G H3C(H2C)7 L1376-5G OH L1376-10G H OH E3385-1G L1376-25G CH3 O E3385-5G H Linolenic acid O L2376-500MG Glutaryl coenzyme A NH2 G9510-5MG H3C CH (CH ) CH OH L2376-5G lithium salt, min. 90% N N G9510-10MG 2 2 5 2 O O O H3C CH3 L2376-10G O P O P O N N • xLi+ HN O OH OH OH Linolenic acid O 62170-10ML-F O OH H3C O CH (CH ) CH OH 62170-50ML-F O N P OH 2 2 5 2 H S OH OH γ-Linolenic acid O L2378-10MG O O CH3(CH2)3CH2 OH L2378-100MG n-Heptadecanoyl O H1385-5MG L2378-500MG S CH2(CH2)14CH3 coenzyme A lithium salt N H L2378-1G O NH2 NH N N HO Linoleoyl coenzyme A - L9754-10MG O O O N N H3C O P O P O O lithium salt, min. 85% H3C OH OH O HO P O OH OH Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 15

Name Structure Cat. No. Name Structure Cat. No. Malonyl coenzyme A NH2 M4263-5MG Oleoyl coenzyme A - O1012-5MG N N lithium salt O O OH M4263-10MG lithium salt H H O O N O1012-10MG N N N HO S O P O P O CH3 O M4263-25MG O O H3C OH OH 2-Oleoylglycerol - M2787-1MG O M4263-100MG • xLi HO P O OH M2787-5MG OH M2787-10MG Palmitoleoyl coenzyme A - P6775-5MG

lithium salt P6775-10MG Malonyl coenzyme A NH2 63410-10MG-F Palmitoyl coenzyme A NH2 P9716-5MG tetralithium salt N N 63410-50MG-F lithium salt O N N P9716-10MG O H C CH3 O O H3C CH3 O O 3 N N O P O P O O N P9716-25MG HN O HN P O P O N OLi OLi O OH O OH OH OH P9716-100MG LiO P O OH S OH O O OH O N OLi O N P OH H H O O S CH2(CH2)13CH3 OLi β-Methylcrotonyl - M3013-10MG O coenzyme A lithium salt M3013-25MG n -Propionyl coenzyme A NH2 P5397-5MG lithium salt N O O N P5397-10MG O H3C CH3 NH2 Methylmalonyl M1762-1MG O P O P O N N P5397-25MG N N HN + O O OH O • xLi coenzyme A tetralithium H H O O M1762-5MG OH OH N N N N OH salt hydrate LiO S O P O P O O CH3 M1762-25MG O CH3 O O H3C OLi OLi S O OH OH O N CH3 P OH O H • xH2O HO P OLi O OH O Sodium stearate O S3381-1G

CH3(CH2)15CH2 ONa S3381-5G S3381-25G Myristoyl coenzyme A NH CH2 CH2 SC CH3 M4414-5MG CO O lithium salt, min. 80% NH2 O CH2 Stearic acid S4751-1G

CH2 N N CH3(CH2)15CH2 OH S4751-5G NH N CO N S4751-10G HO CH O O S4751-25G CH3 C CH2 O P O P O CH2 O CH3 OH OH S4751-100G

xLi OOH Stearoyl coenzyme A NH2 S0802-5MG HO P OH lithium salt N N S0802-10MG O O O H3C CH3 N N S0802-25MG HO O P O P O OH OH O • xLi+ Nervonic acid (CH ) COOH N1514-100MG O NH 2 13 O H C(CH ) 3 2 7 HO P O OH Octanoyl coenzyme A O O6877-5MG OH O NH NH2 lithium salt hydrate S CH2(CH2)5CH3 • xH2O O6877-10MG S CH2(CH2)15CH3 N N C OH O6877-25MG H O O O HN N N N O P O P O O CH3 Succinyl coenzyme A NH2 S1129-5MG O O H3C O O Li sodium salt, Minimum N Li Li O OH O O N S1129-25MG O H3C CH3 O P OH 85% O P O P O N N • xNa O HN O OH OH OH O O 1-Oleoyl-2-acetyl- sn - O O6754-5MG S O OH O CH O O N OH P OH glycerol 2 O6754-10MG H H3C C O C H O OH O6754-25MG CH2OH

16

Terpenoid Metabolism The starts with the formation of acetoacetyl CoA from two molecules of acetyl CoA via Claisen condensation by H3C H CH3 H3C acetyl-CoA C-acetyltransferase. Acetoacetyl CoA is then condensed

H with a third molecule of acetyl CoA in an aldol-like reaction catalyzed H2C by hydroxymethylglutaryl-CoA synthase, followed by hydrolysis, The 20,000+ found in animals, plants, , fungi, to give the metabolite 3-hydroxy-3-methylglutaryl-CoA. In the and are all based on multiples of the 5-carbon third step, NADPH-dependent reduction of the thioester group subunit. This is due to biosynthetic pathways that utilize isopentenyl catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase yields pyrophosphate (IPP) or its isomer dimethylallyl pyrophosphate mevalonate. Mevalonate is phosphorylated at the primary hydroxy (DMAPP) as isoprene building blocks for condensation reactions. group by to form mevalonate-5-phosphate, which undergoes a second kinase reaction to form mevalonate- OH 5-pyrophosphate. A final phosphorylation at the tertiary hydroxyl H C O O OH 2 P P OH group, catalyzed by mevalonate-5-diphosphate decarboxylase, with CH3 O O

• 3NH3 the simultaneous loss of carbon dioxide and phosphate results in 3-isopentenyl pyrophosphate. O O + H3C O P O P O • 3NH4 In contrast to the extensively studied and historic mevalonate O O CH3 pathway, the MEP pathway was only discovered in the 1990′s and is used by bacteria, , and chloroplasts.1 The first step Depending on the biological and the , two consists of the 1-deoxy-D -xylulose-5-phosphate synthase-catalyzed different metabolic pathways exist for the biosynthesis of isopentenyl coupling of pyruvate with D -glyceraldehyde-3-phosphate to give pyrophosphate: 1-deoxy-D -xylulose-5-phosphate (DOXP) with concurrent loss of • the mevalonate pathway and carbon dioxide. Next, an NADPH-dependent rearrangement and • the non-mevalonate or methyl D -erythritol 4-phosphate (MEP) reduction reaction is catalyzed by deoxyxylulose-5-phosphate pathway. reductoisomerase to produce methyl-D -erythritol 4-phosphate (MEP). MEP is conjugated with cytidine triphosphate (CTP) to produce 4-diphosphocytidyl--methyl-D -erythritol. This intermediate

D-Glyceraldehyde- Caption Text? O O 3-phosphate O Acetyl-CoA HS-CoA O O + - COO- H OPO3 S CoA CoA S Pyruvate H Acetyl-Coenzyme A Acetoacetyl-Coenzyme A HO Acetyl-CoA CO2

HS-CoA HO H 2 NADP+ 2 NADPH O H3C H C O O OH O 3 OH - OPO3

-O OH -O S CoA HO H (R)-Mevalonate (3S)-3-Hydroxy-3-methylglutaryl-Coenzyme A 1-Deoxy-D-xylulose-5-phosphate ATP O O- NADPH

ADP P NADP+ O H C O 3 OH O O H3C O H3C OH P HO -O O P O- - HO O O - (R)-Mevalonate-5-phosphate OPO3 O- 2C-Methyl-D-erythritol- H ATP 2,4-cyclophosphate HO HO H 2C-Methyl-D-erythritol- ATP ADP 4-phosphate ADP O H3C OH O O O O

-O O P O P O- - CO2 O P O P O (R)-Mevalonate-5-pyrophosphate O- - - O Isopentenyl-pyrophophate O O- Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 17

undergoes additional phosphorylation at the 2-position of the Name Structure Cat. No.

CH CH CH CH erythritol moiety (4-diphosphocytidyl-2C-methyl-D -erythritol Geranylgeranyl 3 3 3 3 O G2543-5VL

monophosphate H3C O P ONH4 2-phosphate) with subsequent enzymatic cylization and loss of ONH ammonium salt solution 4 cytidine monophosphate. This metabolite is finally converted to Geranylgeranyl O O G6025-1VL isopentenyl pyrophosphate by the action of two enzymes that OPOPO- pyrophosphate + G6025-5VL O- O- 3NH4 reduce the cyclodiphosphate intermediate to a diphosphate and ammonium salt

CH3 CH3 subsequent pyrophosphate. Geranyl monophosphate O G2293-1VL ammonium salt solution H3C O P ONH4 G2293-5VL Another important step in the biosynthesis of terpenoids is the ONH4 isomerization of isopentenyl pyrophosphate to dimethylallyl - G6772-1VL pyrophosphate catalyzed by isopentenyl pyrophosphate isomerase. ammonium salt G6772-5VL α-Humulene CH3 53675-1ML These two fundamental metabolites are joined to form geranyl CH3 53675-5ML pyrophosphate (GPP). GPP can be elongated with another molecule CH3 of isopentenyl pyrophosphate to (FPP) H C through sequencial condensation by farnesyl pyrophosphate 3 Isopentenyl phosphate O 18629 synthetase. Terpenoids with up to 5 isoprenoid units (25 ) can dilithium salt H2C O P OLi OLi be synthesized in this manner, while structures with higher numbers CH3 of carbon atoms are formed by dimerization of the corresponding Isopentenyl OH I0503-1VL H C O O OH pyrophosphate 2 P P I0503-5VL building blocks. OH triammonium salt solution CH3 O O Reference: • 3NH3 1. Hunger, W.N., et al., Structure and reactivity in the non-mevalonate pathway of iso- Isopentenyl O O 00297 prenoid biosynthesis. Biochem. Soc., Trans ., 31 , 537 (2003). pyrophosphate trilithium H2C O P O P OLi OLi OLi salt CH3

( R )-(+)- CH3 183164-5ML Name Structure Cat. No. H2C 183164-100ML H3C β-Carotene CH CH CH 22040-1G-F 183164-500ML 3 3 3 H C CH3 3 22040-5G-F CH CH CH CH CH3 3 3 3 3 22040-25G-F ( S )-(−)-Limonene 218367-50G CH3 H C 218367-250G 2 CH3 (−)-trans - H3C H 22075-1ML-F CH CH CH CH CH 3 3 3 3 3 L9879-1MG H C 22075-5ML-F CH3 3 H3C 22075-25ML-F CH3 CH3 CH3 CH3 L9879-5MG H L9879-10MG H2C (−)- H3C OH 15785-100G 1-Deoxy-D -xylulose OH O 14764-10MG HO CH3 15785-1KG CH3 OH CH3

1-Deoxy-D -xylulose-5- O OH O 13368-1MG (−)-Menthone O CH3 218235-25G HO P O + phosphate sodium salt CH3 • xNa 13368-5MG CH3 218235-100G OH OH H3C γ,γ-Dimethylallyl O O D4287-1VL + 2-C-Methyl-D -erythritol OH 41707 H C O P O P O • 3NH4 pyrophosphate 3 D4287-5VL OH O O HO triammonium salt CH3 H3C OH

trans,trans -Farnesol H3C OH 277541-1G ( R )- sodium H3C OH O 41288-50MG CH CH CH 277541-10G 3 3 3 salt HO ONa 41288-10MG

Farnesyl monophosphate CH3 CH3 CH3 F1803-5VL O (±)-Mevalonic acid H3C OH O 79849-10MG ammonium salt solution O H3C O P ONH4 5-phosphate trilithium salt LiOP O OLi 79849-50MG ONH4 hydrate OLi • xH2O

Farnesyl pyrophosphate O O F6892-1VL ( R )-Mevalonic acid HO CH3 O 77631-50MG - O O ammonium salt OPOPO + F6892-5VL 5-pyrophosphate - - 3NH4 LiO P O P O OLi 77631-10MG O O tetralithium salt OLi OLi Geraniol H3C OH 163333-25G (±)-Mevalonic acid H3C OH O 94259-10MG CH 163333-100G O O 3 CH3 5-pyrophosphate LiO P O P O OLi 94259-50MG Geranylgeraniol - G3278-100MG tetralithium salt OLi OLi

( R )-(−)-Mevalonolactone H3C OH 68519-100MG 68519-500MG O O 18

Name Structure Cat. No. Name Structure Cat. No.

(±)-Mevalonolactone HO CH3 M4667-1G - B4936-5MG

M4667-5G CH3 C5157-1MG O O M4667-10G CH3 CH3 C5157-5MG CH3 CH3 cis -Nerolidol CH3 CH3 72180-25ML C5157-10MG H3C H H3C HO H H CH 2 HO CH3 H C CH 2,3-Oxidosqualene CH3 CH3 41043-1MG 3 3 C9756-1G H3C CH3 H3C H CH C9756-5G CH3 41043-10MG 3 CH3 CH3 CH3 O 41043-50MG H H3C OH H Phytol, mixture of isomers 80191-100ML H (~2/1: trans/cis) CH CH 3 3 CH3 CH3 CH2

CH (−)-α-Pinene 3 P45702-5ML HO H P45702-100ML H3C P45702-500ML 5α-Cholest-7-en-3β-ol - C3652-25MG H3C C3652-100MG (R )-(+)- O CH3 376388-5G CH3 CH3 C8667-500MG CH3 376388-100G CH3 CH3 C8667-1G H3C H3C H H C8667-5G S3626-10ML H H C8667-25G HO S3626-100ML C8667-100G

S3626-500ML Cholesterol CH3 CH3 C8503-25G S3626-1L CH3 CH3 C8503-100G H3C H H C8503-500G H H (+)-α-Terpineol CH3 83073-5ML-F C8503-1KG HO H3C OH C8503-5KG Cholesteryl arachidonate - C8753-10MG C8753-25MG CH 3 C8753-500MG

CH CH Cholesteryl hexanoate H 3 3 C6524-25G H3C CH3 C6524-100G H3C H Metabolism O H H

H3C O

CH3 CH3 H C 3 CH CH H 3 3 CH3 Cholesteryl linoleate H3C C0289-100MG CH3 H3C H H H3C H O C0289-250MG CH3 H H H H CH3(CH2)3CH2 CH2(CH2)5CH2 O C0289-1G HO

The biosynthesis of originates with farnesyl pyrophosphate Cholesteryl oleate H3C C9253-100MG H C 3 H C9253-250MG through reductive dimerization to squalene by squalene synthase CH3 H3C H C9253-500MG and a subsequent enzymatic conversion of squalene to . H3C H H C9253-1G Enzymatic epoxidation of squalene by squalene epoxidase then O yields (3S)-2,3-oxidosqualene. Subsequent by oxidosqualene- O CH (CH ) CH 2 2 5 2 CH2(CH2)6CH3 lanosterol cyclase generates four rings, six carbon-carbon bonds, CH3 CH3 Cholesteryl palmitate H C6072-1G H3C and seven chiral centers in one enzymatic reaction and results in a CH3 C6072-10G H3C H O tetracyclic steroid frame. H H

CH3(CH2)13CH2 O

H3C H3C CH3 CH3 O O CH3 CH CH CH H CH CH H CH3 O O O 3 3 3 3 CH H CH3 3 P P 3 O CH3 CH CH CH CH Corticosterone C2505-500MG H C 3 H C 3 CH3 3 CH CH3 H 3 O O 3 3 CH3 3 OH CH 3 H3C CH3 CH 3 CH H H HO CH3 CH3 3 H OH OH O H OH H3C CH3 H H3C H3C CH3 H3C CH 3 H3C CH 3 chol H

Farnesyl pyrophosphate Squalene(3S)-2,3-Oxidosqualene Lanosterol Cholesterol H H O O C2755-250MG CH O 3 OH C2755-1G H3C H HO C2755-5G H H O Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 19

Name Structure Cat. No. Name Structure Cat. No. H C CH H C 7-Dehydrocholesterol 3 3 D4429-1G 3 CH 45480-10G-F H C 3 3 H H3C CH3 D4429-5G H 45480-50G-F CH3 H3C H3C H3C H H H H HO HO

21-Deoxycortisol O P9521-25MG trans,trans -Farnesol H3C OH 277541-1G H C OH HO 3 CH3 CH3 CH3 CH3 277541-10G H3C H Farnesyl pyrophosphate O O F6892-1VL H H ammonium salt OPOPO- O 3NH + F6892-5VL O- O- 4 1-Deoxy-D -xylulose-5- O OH O 13368-1MG Geraniol H3C OH 163333-25G HO P O + phosphate sodium salt CH3 • xNa 13368-5MG OH CH3 CH 163333-100G OH 3 - D6513-5MG Geranylgeranyl O O G6025-1VL OPOPO- + pyrophosphate - - 3NH D6513-10MG O O 4 G6025-5VL ammonium salt H3C 1α,25-Dihydroxyvitamin D3 17936-100UG-F H3C Geranyl pyrophosphate - G6772-1VL CH3 17936-1MG-F ammonium salt G6772-5VL H3C OH O H Hydrocortisone OH H0135-1MG H3C HO OH H C CH2 3 H H H HO OH O 1α,25-Dihydroxyvitamin D H3C 17944-1MG-F 2 CH3 22(R)-Hydroxycholesterol - H9384-1MG H3C CH3 H9384-5MG H3C OH CH3 CH3 22(S)-Hydroxycholesterol H H5884-5MG H H3C CH3 H5884-10MG H3C H OH CH2 H H HO OH HO

(24R)-24,25- H3C OH 17943-100UG 17α-Hydroxypregnenolone - H5002-5G H3C Dihydroxyvitamin D CH3 17943-1MG 3 1α-Hydroxyvitamin D CH3 CH3 17946-1MG 3 H C H H3C OH 3 CH3 H

H CH2

CH HO 2 γ,γ-Dimethylallyl O O D4287-1VL HO OH + H C O P O P O • 3NH4 pyrophosphate 3 D4287-5VL Isopentenyl OH I0503-1VL O O OH triammonium salt CH H2C O O 3 pyrophosphate P P I0503-5VL OH triammonium salt solution CH3 O O Doxercalciferol CH3 CH3 D0196-1MG CH3 • 3NH3 CH3 D0196-5MG H CH3 Lanosterol L5768-1MG H H L5768-5MG

CH2 HO HO OH H

CH3 CH3 H C OH O , activity: 95220-1G (±)-Mevalonic acid O 3 79849-10MG CH3 5-phosphate trilithium salt ~40000 units/mg CH3 95220-5G LiOP O OLi 79849-50MG H CH3 hydrate OLi • xH2O H (±)-Mevalonic acid H C OH O 94259-10MG O O 3 5-pyrophosphate 94259-50MG CH2 LiO P O P O OLi tetralithium salt OLi OLi HO 2,3-Oxidosqualene CH3 CH3 41043-1MG H C CH3 - 3 Ergosta-5,7,9(11),22- E2634-5MG CH3 CH3 CH3 CH3 O 41043-10MG tetraen-3β-ol E2634-50MG 41043-50MG

Ergosterol H3C E6510-5G CH CH3 5-Pregnen-3β-ol-20-one O 3 P9129-1G H3C H C H E6510-10G 3 CH P9129-5G H C 3 3 E6510-25G H3C H H3C P9129-25G H H H H P9129-100G HO HO 20

Name Structure Cat. No. Name Structure Cat. No.

CH CH CH β-Sitosterol H3C 3 S1270-10MG Cholesterol 3 3 20808-100G-R CH3 H3C CH3 S1270-25MG CH3 20808-1KG-R CH H3C H H3C H 3 S1270-100MG H H H H H HO HO OH CH Cholic acid C1129-25G β-Sitosterol H3C 3 S9889-1MG CH H3C C1129-100G H3C 3 S9889-5MG HO O CH3 CH C1129-500G H3C H 3 S9889-10MG H3C H C1129-1KG H H H H HO HO OH H Squalene S3626-10ML

S3626-100ML Glycocholic acid hydrate HO CH3 O G2878-100MG S3626-500ML H CH3 N OH G2878-500MG S3626-1L H C H 3 O G2878-1G

H H • xH2O G2878-5G CH3 CH3 HO OH H S4297-1G H H3C G2878-25G CH3 S4297-5G H3C H 25-Hydroxycholesterol CH3 HO CH3 H1015-10MG H C H H3C 3 H H CH3 H1015-25MG H3C H HO H1015-100MG H H H

Stigmasterol CH3 CH3 S2424-1G HO H3C

CH3 S2424-5G Sodium deoxycholate HO CH3 30968-25G H C 3 H H S2424-10G CH3 ONa CH3 monohydrate H C • H2O H H S2424-25G 3 H H O HO H H HO H

Sodium glycochenode- Na+ -O G0759-25MG Acid Metabolism O oxycholate G0759-100MG H3C NH CH3 G0759-500MG H H C H3C OH 3 O G0759-1G H C H3C H 3 H O G0759-10G H H H G0759-25G HO OH HO OH H H

Sodium H3C HN O T6260-100MG Mammalian cells use multiple biochemical pathways to break down CH taurochenodeoxy cholate 3 S O T6260-250MG O O- cholesterol into more polar, water-soluble bile acids that can H3C T6260-1G Na+ as emulsifying agents. A series of enzymatic reaction steps involving H H T6260-5G HO OH 7α-hydroxylations, epimerization of the 3β-, saturation H

Taurocholic acid sodium CH3 T9034-1G of the double bond, and side-chain cleavage or oxidation convert H C H H O HO 3 N salt hydrate SONa T9034-5G cholesterol into the chenodeoxycholic acid. H C 3 H O O T9034-25G O 7-Deoxycholic acid is formed along a similar pathway, with an H H H H HO OH additional 12α-hydroxylation and removal of the 7-hydroxy group. The H Ursodeoxycholic acid CH3 U5127-1G H hydrophobic/hydrophilic balance of the various bile acids facilitate the H3C OH U5127-5G H C solubilization of monoacylglycerols, -soluble , and other 3 H O U5127-25G lipids. This helps and absorption but is also required for H H HO OH solubilization and excretion of lipophilic metabolites such as . H Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 21

Isotopically Labeled Metabolites

Isotopically Labeled Metabolites

As the body′s major source of fuel, the study of fat metabolism is Name Structure Cat. No. 13 CH3 CH3 an area of interest and importance. The increased availability of Cholesterol-3,4- C2 488585 CH3 stable isotopically labeled fatty acids and related compounds has CH3 aided in the steady accumulation of information surrounding lipid H3C H H H H metabolism. Labeled fatty acids have been used in numerous research 13C HO 13C areas including fatty acid oxidation1 , lipid kinetics2 , quantitative lipid analyses3 , lipid synthesis4 , and fat absorption.1 Information gathered 13 CH3 CH3 Cholesterol-3,4- C2 662291 from stable isotope tracer studies has added to our understanding of CH3 CH3 the metabolic pathways and the metabolic fate of certain fatty acids. H3C H H

H H The safe labeling of lipids by non-radioactive isotopes has been 13C HO 13C crucial for advancements in the study of the

of membranes, magnetic resonance imaging and spectroscopy, 13 Cholesterol-4- C H3C 605875 13 H3C science, and metabolomics. The availability of C- and H CH3 15 H3C H N-labeled lipids and lipid precursors has enabled selective H3C isotope labeling of membranes by biosynthetic incorporation of a H H HO 13C labeled lipid. Lipid metabolism can therefore be studied in several 13 Cholesterol-25,26,27- C H3C 13 707678 3 CH3 dimensions: at the whole organism level, at the level of individual H3C 13C H H3C 13 membranes, or in the small molecule pathways of lipid conversions. H CH3 References: H H 1. Wolfe, R.R. and Chinkes, D.L.; Isotope Tracers in Metabolic Research, Principles and Practice of HO nd Kinetic Analysis , 2 ed.; John Wiley & Sons, Inc.: Hoboken, New Jersey, 2005; pp 259-298. Cholesterol- H3C 679046 CD3 H3C 2. Adiels, M., Larsson, T., Sutton, P., Taskinen, M.-R., Borén, J., and Fielding, B.A.; Rapid Com- 26,26,26,27,27,27-d6 CD3 mun. Mass Spectrom . 2010 , 24 , 586-592. H3C H

3. Sun, D., Cree, M.G., and Wolfe, R.R.; Anal. Biochem . 2006 , 349 , 87-95. H H 4. Bergman, B.C., Perreault, L., Hunerdosse, D.M., Koehler, M.C., Samek, A.M., and Eckel, R.H.; HO J. Appl. Physiol . 2010 , 108 , 1134-1141. CH CD H 3 3 Cholesteryl- H3C 730238 5. Jauregui, R.C., Mattes, R.D., and Parks, E.J.; Gastroenterology 2010 , in press. CD3 26,26,26,27,27,27-d H3C H 6 O H H H3C linolenate CH2(CH2)5CH2 O Name Structure Cat. No.

13 O Acetyl-1,2- C2 coenzyme 658650 13C NH A lithium salt S 13 2 C Cholic-2,2,3,4,4-d acid CH3 614106 H N 5 HO O N O O N CH3 OH

CH3 O POP O N + H3C H3C N • xLi D H O OH OH O D HN H H OH O D OH HO P O OH HO H O D D OH Cholic acid-2,2,4,4-d OH CH3 614149-500MG Cholesterol-2,2,3,4,4,6-d CH3 CH3 488577-100MG 4 6 CH3 OH CH3 CH3 D H3C H H O D H3C H H D D H H H H H HO HO OH D D D D D D 22

Name Structure Cat. No. Name Structure Cat. No. 13 Cholic-24- C acid HO CH3 605883 O D D D D O rac -Glyceryl-d5 -2,3- 730076 CH CH3(CH2)6CH2 CH2(CH2)5CH2 O O CH2(CH2)13CH3 3 OH D 13 O C dioleate-1-palmitate CH2(CH2)5CH2 CH2(CH2)6CH3 H C O 3 H H O H H

HO OH H 13 Glyceryl tri(octanoate- H3C(CH2)6 CO2 425893 15 CH 13 13 Choline chloride- N 3 609269-1G 1- C) H3C(CH2)6 CO2 15 HO N CH3 13 H3C(CH2)6 CO2 Cl CH3 O O Glyceryl tri(octanoate-d15 ) 617121 13 Choline chloride-1- C 13 CH3 605301 C CD3(CD2)5CD2 O O CD2(CD2)5CD3 HO N CH3 Cl O CD2(CD2)5CD3 CH3 O

Choline chloride-1,1,2,2-d D CH3 615544 4 D HO NCH Cl 13 13 3 Glyceryl tri(oleate-1- C) H3C(CH2)7HC=HC(CH2)7 CO2 489514-500MG CH3 13 D D H3C(CH2)7HC=HC(CH2)7 CO2 H C(CH2) HC=HC(CH ) 13CO Choline chloride- CD3 492051-1G 3 7 2 7 2 trimethyl-d 13 13 9 D3CNCD3 • Cl Glyceryl tri(oleate-1- C) H3C(CH2)7HC=HC(CH2)7 CO2 714771 13 H3C(CH2)7HC=HC(CH2)7 CO2 13 OH H3C(CH2)7HC=HC(CH2)7 CO2

H C(CH ) H13C=13CH13CH 13CH (CH ) 13CH 13CH 13CO Cortisone- D O 705586-5MG Glyceryl tri(oleate- 3 2 7 2 2 2 3 2 2 2 646253 D CH 13 13 13 13 13 13 13 13 3 OH 1,2,3,7,8,9,10- C ) H3C(CH2)7H C= CH CH2 CH2(CH2)3 CH2 CH2 CO2 2,2,4,6,6,9,12,12-d8 O 7 13 13 13 13 13 13 13 D H3C H HO H3C(CH2)7H C= CH CH2 CH2(CH2)3 CH2 CH2 CO2 D D H 13 13 O Glyceryl tri(oleate-9,10- H3C(CH2)6H2CH C=H C(CH2)7CO2 646245 D D 13 13 13 D C2 ) H3C(CH2)6H2CH C=H C(CH2)7CO2

13 13 1α,25-Dihydroxyvitamin D CH3 CH3 705942-1MG H3C(CH2)6H2CH C=H C(CH2)7CO2 3 HO (6,19,19-d ) CH3 3 CH3 Glyceryl tri(palmitate-1-13 C) O 425907-1G H 13C O CH2(CH2)13CH3 H D O O O O 13C 13C CD2 CH2(CH2)13CH3 CH2(CH2)13CH3 HO OH Glyceryl tri(palmitate-1-13 C) O 680842 13C Ethanolamine-15 N 15NH 609552 O CH2(CH2)13CH3 HO 2 O O O O 13C 13C 13 13 Ethanolamine- C HO C 606294 CH2(CH2)13CH3 CH2(CH2)13CH3 2 13 C NH2 13 13 Glyceryl tri(palmitate- H3C(CH2)13 CH2 CO2 605603 Ethanolamine-2-13 C HO 13C 606316 13 13 13 NH2 1,2- C2 ) H3C(CH2)13 CH2 CO2

13 13 13 H N 13C H3C(CH2)13 CH2 CO2 Ethanolamine- C2 2 606308-100MG 13C OH • HCl hydrochloride Glyceryl tri(palmitate- O 615471 D D D D Glycerol-1,1,2,3,3-d5 454524-1G 16,16,16-d3 ) O CH2(CH2)13CD3 HO OH 454524-5G CD3(CH2)13CH2 O O CH2(CH2)13CD3 D OH O O D D D D Glycerol-1,1,2,3,3-d5 661473 O O HO OH Glyceryl tri(palmitate-d31 ) 616966 D OH CD3(CD2)13CD2 O O CD2(CD2)13CD3 O Glycerol-1,2-13 C 13C 714895 CD (CD ) CD 2 HO 13C OH 2 2 13 3 O OH Glyceryl tri(palmitate-d ), O O 660698 Glycerol-1,3-13 C 13C 13C 492639-250MG 31 2 HO OH S&P tested CD3(CD2)13CD2 O O CD2(CD2)13CD3 OH O CD2(CD2)13CD3 13 Glycerol-2- C OH 489484 O HO 13C OH 13 13 Glyceryl tri(stearate-1- C) H3C(CH2)16 CO2 492663-250MG 13 OH Glycerol-2- C 661465 H C(CH ) 13CO HO 13C OH 3 2 16 2 13 H3C(CH2)16 CO2 13 13 13C Glycerol- C3 C 489476-500MG HO 13C OH Glyceryl tri(stearate- O O 616117 18,18,18-d ) OH 3 CD3(CH2)15CH2 O O CH2(CH2)15CD3 O CH2(CH2)15CD3 13 13 13C Glycerol- C3 C 660701 HO 13C OH O OH Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 23

Name Structure Cat. No. Name Structure Cat. No.

13 Glycocholic acid-glycyl- O 605891 Oleoyl- C coenzyme A NH2 675768 HO CH3 18 13 H N N 1- C CH3 N 13C lithium salt OH H C CH O O H C 3 3 N N 3 H H O HO O P O P O OH OH O • xLi+ H H O NH O HO OH H HO P O OH OH O NH 13C 13C O 13 13 13 13 13 13 Hydrocortisone-1α,2α-d2 614157 S CH2( CH2)5 CH2 CH2( CH2)6 CH3 H C OH 13C HO 3 O D OH CH H D 3 H H O 13 Palmitoyl-1- C coenzyme NH2 658200 Hydrocortisone- O 705594-5MG N D D A lithium salt N HO CH3 OH 9,11,12,12-d 705594-10MG O H C O O 4 3 CH3 N N D H HO O P O P O NH O OLi OLi D H OH H3C O O LiO P O OH O NH Linoleic acid-13 C O 605735-100MG OH 18 S 13C 13 CH2(CH2)13CH3 13 13 13 13 13 13 13 CH3( CH2)3 CH2 C CH2( CH2)5 CH2 OH C 13 13 13 13 C C C C O

13 O Potassium linoleate- C18 605816 13 O Linolenic Acid-1- C 694940 13C 13 13 13 13 H C C CH2( CH2)5 CH2 OK 3 13C CH2(CH2)5CH2 OH 13 13 O C Linolenic acid- C18 605743-100MG 13 13C CH2 13 13 13 13CH (13CH ) 13CH OH C C C 2 2 5 2 13 H 13C 13C 13C 13C 13C 13C 13C C 3 13CH (13CH ) 13CH 13C 2 2 3 3

13 13 OH O O 1,2-Propanediol-1,2- C2 603678 Malonyl- C3 coenzyme A 655759 13C 13 NH 13 lithium salt 13 C 2 C OH S C OH 13 H N H3C C O N O O N CH D D 3 O POP O N N + 1,2-Propane-d6 -diol 614416 H3C • xLi D C OH OH O 3 OH HN OH O HO D O HO P O OH 1,2-Propanediol-d D 486272-5G OH 8 OD CD DO 3 Octanoyl-2,4,6,8- 13 C O 703885 4 D D Coenzyme A, lithium salt NH2 S 13C 13C 13C 13CH 3 N 13 13C 13C N 1,3-Propanediol-1,3- C2 603554 OH HO OH H O O HN N N N O P O P O 1,3-Propanediol-2-13 C 13CH 491101 O HO 2 OH CH3 O O H3C O O Li 13 13C 13C Li Li O OH 1,3-Propanediol- C3 603562 HO 13C OH O P OH

O HOCD2CD2CD2OH 1,3-Propane-d6 -diol 613525 13 Oleic acid-1- C O 661589 DOCD2CD2CD2OD 1,3-Propanediol-d8 589535 13C OH 13 CH2(CH2)5CH2 H 13C 13C 1-Propanol- C3 3 640689 13C OH CH2(CH2)6CH3 Propionaldehyde-1-13 C O 603813 13 13 Oleic acid-9,10- C O 646466 H3C C 2 H 13C 13C CH3(CH2)6CH2 CH2(CH2)5CH2 OH O Propionaldehyde-2,2-d2 588113 13 O H3C Oleic acid- C18 490431-100MG H 13 C D D 13 13 13 OH 13 CH2( CH2)5 CH2 C Propionaldehyde- O 707201 13 D C C 2,2,3,3,3-D 3 H 13 13 13 5 CH2( CH2)6 CH3 D D

O 13 O Oleic acid-d34 683582 Stearic acid-1- C 299162-1G 13C D CD (CD ) CD OD 2 2 5 2 CH3(CH2)15CH2 OH

13 O D CD2(CD2)6CD3 Stearic acid-1,2- C2 591602 13C 13 CH3(CH2)15 CH2 OH Stearic acid-2-13 C O 591491 13 CH3(CH2)15 CH2 OH 24

Name Structure Cat. No. Name Structure Cat. No. O Stearic-d acid O 448249-250MG Stearic acid-2,2-d2 493155-1G 35 OH CD3(CD2)15CD2 OH 448249-1G D D 13 Stearoyl- C coenzyme A NH2 675776 Stearic-17,17,18,18,18-d O 615846 18 5 lithium salt N N acid CD3CD2(CH2)14CH2 OH O O H3C CH3 N N HO O P O P O Stearic acid-18-13 C O 605654 OH OH O • xLi+ 13CH (CH ) CH OH O NH 3 2 15 2 O Stearic acid-13 C O 605581-100MG HO P O OH 18 OH 13 13 13 13 C O NH CH3( CH2)15 CH2 OH S 13CH (13CH ) 13CH 13C 2 2 15 3 Stearic acid-18,18,18-d - 490393-250MG 3 O

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Characteristic Metabolites for Inborn Errors of Lipid Metabolism

Characteristic Metabolites for Inborn Errors of Lipid Metabolism

Hereditary disorders in lipid metabolism include Tay-Sachs Nine inborn errors of bile acid metabolism have been identified that disease, Gaucher disease, Niemann-Pick disease, metachromatic result in enzyme deficiencies and damaged bile acid biosynthesis in leucodystrophy, , Refsum disease, and Tangier disease. infants, children, and adults. Since bile acids have several important These lipidoses are characterized by dysfunctional lipid metabolism physiological functions, such as emulsifying fats and fat-soluble and result in abnormal metabolite accumulations. One of the first vitamins, and involvement in cholesterol, bilirubin, , and disorders recognized as an inborn error of lipid metabolism was drug metabolites elimination, a failure in the multistep enzymatic Refsum disease, which produces toxic levels of phytanic acid if conversion of cholesterol to bile acids will accumulate unusual bile untreated. acids and metabolic intermediates. Gaucher disease is a progressive sphingolipid-degradation Name Structure Cat. No. disease characterized by genetic in the lysosomal O-Acetyl-L - A6706-1G hydrochloride A6706-5G enzyme , which leads to decreased enzymatic N, N -Dimethylglycine CH3 O D1156-10MG activity. Measurements of the metabolites methylcholine, N H3C OH D1156-5G phosphatidylcholine, and sphingomyelin are important for studying D1156-10G the pathophysiology of Gaucher disease. The main therapy used D1156-25G

N,N -Dimethylglycine CH3 O D6382-5G to treat Gaucher disease is enzyme-replacement therapy in order N hydrochloride • HCl D6382-25G to normalize sphingolipid degradation and to prevent H3C OH damage caused by sphingolipid accumulation. Another promising Globotriaosylsphingosine - G9534-1MG therapeutic approach to Gaucher disease is to decrease the tissue from porcine blood glucocerebrosidase level to a which can be cleared by DL-Hexanoylcarnitine - H2132-25MG the existing glucocerebrosidase. chloride 3-Hydroxy-3- O O H4392-100MG

A deficiency of the lysosomal enzyme α-galactosidase A results methylglutaric acid HO OH H4392-1G HO CH3 in the progressive accumulation of the glycosphingolipids Palmitoyl- L -carnitine O CH2(CH2)13CH3 P1645-5MG globotriaosylceramide Gb3 and digalactosyl-ceramide in Fabry chloride O O P1645-10MG CH3 P1645-25MG disease, which can cause early from cardiac, renal, and H3C N OH cerebrovascular events. CH3 Cl Palmitoyl- DL -carnitine P4509-100MG Dimethylglycine dehydrogenase (DMGDH) deficiency is an chloride P4509-1G inborn error of choline metabolism caused by a in the Phytanic acid, mixture of - P4060-5MG hDMGDH and results in increased N,N-dimethylglycine isomers P4060-25MG Pristanic acid solution, O P6617-5MG concentrations of 100-fold in and 20-fold in . H C mixture of isomers 3 OH CH3 CH3 CH3 CH3

26

Lipid Metabolites as Biomarkers for the Diff erentiation of Diseased and Healthy Cells

Lipid Metabolites as Biomarkers for the Differentiation of Diseased and Healthy Cells

The human body regulates cellular lipid concentrations by location results from acidic sphingomyelinase deficiency in Niemann-Pick and time, and deregulation is associated with a variety of human disease A and B, while cholesterol accumulation occurs in Niemann- diseases. In addition to disorders due to inborn errors of lipid Pick disease C due to mutations in either the NPC1 or NPC2 . metabolism, diseases like cardiovascular disease, diabetes, cancer, Cholesterol is an important regulator of lipid organization and , and neurodegenerative diseases are frequently lipid a precursor for biosynthesis. The gene encoding related. A key feature of diabetes, , and the apolipoprotein E4 variant of the principal cholesterol carrier is excessive lipid accumulation in cells. Excess energy is stored protein in the brain (the E4 allele of APOE ) is a significant risk factor as triacylglycerols for later use when are scarce. These for Alzheimer′s disease. Lipid peroxidation due to phospholipase triacylglycerols, along with the precursors to membrane lipids, are activation may contribute in part to Parkinson′s disease. stored in cytoplasmic lipid droplets in eukaryotic cells. -pathogen Name Structure Cat. No. interactions in lipid metabolism are also of interest in infectious N-Acetyl- D -sphingosine OH A7191-1MG disease research since pathogenic microorganisms can use the host's HO CH2(CH2)11CH3 A7191-5MG lipids as a carbon and energy source, which provides an advantage to H3C NH the pathogen in persistence, virulence, and overcoming host immune O Acrolein O 01679-10ML responses. Major drug classes like the and H2C H (COX) inhibitors target enzymes involved in lipid metabolism. Cholesterol CH3 CH3 C8667-500MG Increased concentrations of lysophosphatidylcholines and decreased CH3 CH3 C8667-1G concentrations of antioxidative ether phospholipids in serum have H3C H H C8667-5G H H C8667-25G been associated with acquired obesity. Detailed analysis of the HO C8667-100G local concentrations of lipids, their precursors, and metabolites as a Cholesterol CH3 CH3 20808-100G-R function of time will aid the understanding of their roles in the vital CH3 CH3 20808-1KG-R functions of cells. H3C H H H H Next to , the central nervous system has the highest HO

Galactocerebrosides from R R=fatty acid C4905-10MG cellular lipid concentration. Injuries and disorders of the CNS may NH CH2OH bovine brain HO C4905-25MG be influenced by changes in lipid metabolism. The accumulation of OO (CH2)12CH3 OH LDL-derived lipids in the arterial wall results in atherosclerosis and is OH OH a risk factor for stroke. Lipid metabolism is altered by tumor necrosis L -α-Glycerophosphoryl- - G5291-10MG factor-α (TNF-α) and interleukin-1 (IL-1), which stimulate production choline G5291-50MG of , ceramide, and reactive species. Reactive G5291-100MG oxygen species that exceed the cell′s capability for N-Hexanoyl- D -sphingosine OH H6524-1MG H6524-5MG result in oxidative yielding oxidized phospholipids that are CH3(CH2)11CH2 OH H3C NH metabolized to 4-hydroxynonenal, 4-oxo-2-nonenal, and acrolein. O Neurodegenerative diseases, CNS injuries, and brain traumas can be HNE-DMA OH H9538-2MG OCH3 influenced by lipid oxidation because of the high lipid content and H3C H9538-5MG oxygen consumption of the brain. Sphingomyelin accumulation OCH3 Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 27

Name Structure Cat. No. Name Structure Cat. No.

D -α-Hydroxyglutaric acid O O H8378-25MG Sphingomyelin S7004-5MG disodium salt NaO ONa H8378-100MG S7004-10MG OH H8378-250MG S7004-50MG

Malondialdehyde H3C CH3 O 63287-1G-F S7004-100MG tetrabutylammonium salt N S7004-500MG CH H O 63287-5G-F H3C 3 Sphingomyelin S0756-50MG - N-Palmitoyl- D - P6778-1MG S0756-100MG sphingomyelin P6778-10MG S0756-500MG semisynthetic from bovine brain sphingomyelin Trisodium (2RS ,3 RS )-2- O ONa 59464-10MG O O methylcitrate 59464-50MG OH N-Octanoyl- D -sphingosine O1882-5MG NaO ONa HO HO CH2(CH2)11CH3 CH3 HN CH2(CH2)5CH3 O

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Altered Lipid Metabolites in Aging

Altered Lipid Metabolites in Aging

The development of cognitive and neurodegenerative disorders, Name Structure Cat. No. cardiovascular diseases, metabolic disorders, bone diseases, certain Cholesterol CH3 CH3 C8667-500MG CH 3 C8667-1G forms of cancer, and autoimmune diseases with increasing age CH3 H3C H H C8667-5G has been associated with the stability of the cell and biochemical H H C8667-25G HO reactions within it. Like DNA and proteins, lipids are sensitive to C8667-100G that produce . Endogenous HNE-DMA OH H9538-2MG OCH3 H9538-5MG , such as malonic dialdehyde and methylglyoxal, are H3C OCH3 the major initiators of metabolic disorders. Age-related diseases Malondialdehyde H3C CH3 O 63287-1G-F N develop when cells cannot control formation or abolish the tetrabutylammonium salt 63287-5G-F H C CH H O negative methylglyoxal effect on their metabolism. Toxic aldehydes 3 3 Methylglyoxal solution O M0252-25ML cause cumulative damage over a lifetime if not counteracted by the H CH3 M0252- cell′s ability to avoid the formation of endogenous aldehydes or O 100ML to neutralize their negative effects without damaging vital cellular M0252- 250ML components. The aging process and the individual′s life span is M0252- influenced by the balance of the two opposing processes of anti- 500ML aging effects and the aging effects of toxic aldehydes. M0252-1L (+)-α-Tocopherol, activity: CH3 T1539-25G HO ≥1000 IU/g CH3 CH3 CH3 Cholesterol levels in human serum above 6.5 mmol/L are known to CH3 T1539-100G be associated with a higher risk of developing Alzheimer′s disease, H3C O CH3 CH3 while a reduction of cholesterol in the serum in midlife lowers the risk of dementia. Bile acids act as regulators of aging that benefit health Xanthophyll OH X6250-1MG X6250-5MG HO and longevity and modulate housekeeping longevity assurance pathways. It is likely that the mechanisms for the positive effects of bile acids are evolutionarily conserved. The time-dependent accumulation of age pigments like lipofuscin occurs in all cells, but it is more prominent in cells which are not active in cell division. These age pigments appear together with lipid droplets in the . Order sigma.com/order Technical service sigma.com/techinfo sigma.com/lifescience 29

Lipid Metabolites in Biosynthesis

Lipid Metabolites in Natural Product Biosynthesis

Many natural compounds contain tailor-made lipid anchors or Name Structure Cat. No. lipid-like functional groups intended to localize them on the cellular Acetyl coenzyme A NH2 A2181-1MG trilithium salt O N membrane. Natural products with lipid anchors are of interest N A2181-5MG S CH3 N A2181-10MG H N for a number of cell migration processes of healthy and diseased - + + O N O Li Li A2181-25MG CH3 O P O O- O OH cells like wound healing, blood vessel formation, immune system H C - Li+ A2181-100MG 3 O P O O HN O O P OH function, and tumor metastasis. Certain lipid components of the OH O cell membrane itself, such as phosphatidylglycerol, cardiolipin, or O glycosylphosphatidylinositol, can also serve directly as anchors. Acetyl coenzyme A NH2 A2056-1MG N sodium salt O O N A2056-5MG These phospholipids are listed in the section on natural abundance H3C CH3 HO O P O P O N N A2056-10MG lipid metabolites. O A2056-25MG OH OH O NH O A2056-100MG • xNa OH Lipids in the cell walls and membranes of pathogenic microorganisms NH O HO P O H3C S and their related pathways are of particular interest for the OH development of novel bioactive compounds, especially if they have O no eukaryotic counterparts. Antibiotics like the phosphoglycolipids Coniferyl alcohol OH 223735- 100MG are the only known inhibitors of the peptidoglycan HO OCH3 223735-1G , which are involved in the biosynthesis of Farnesyl pyrophosphate O O F6892-1VL ammonium salt OPOPO- the bacterial cell wall. The lipoteichoic acids of the cell wall of 3NH + F6892-5VL O- O- 4 Gram-positive bacteria, anchored by their diacylglycerol moiety, Geranylgeranyl O O G6025-1VL are recognized by the , making them an OPOPO- pyrophosphate + G6025-5VL O- O- 3NH4 interesting scaffold for new approaches to natural therapeutic ammonium salt products. In Gram-positive bacteria, lipid A is of interest for the Geranyl pyrophosphate - G6772-1VL ammonium salt G6772-5VL development of immunostimulating compounds and Isopentenyl O O 00297 adjuvants. pyrophosphate trilithium H2C O P O P OLi OLi OLi salt CH The biosynthesis of eicosanoids such as prostaglandins, 3 Isopentenyl OH I0503-1VL thromboxanes, and begins with arachidonic acid and H C O O OH pyrophosphate 2 P P I0503-5VL OH involves a series of enzymatic reactions including radical formation, triammonium salt solution CH3 O O reaction with oxygen and cyclization, and reduction. Polyacetylenic • 3NH3 natural products contain a unique carbon-carbon triple bond and Malonyl coenzyme A NH2 63410- tetralithium salt N 10MG-F have a wide variety of biochemical and ecological functions. Initial N O H3C CH3 O O 63410- N N O P O P O departure points from primary metabolism include the three fatty HN O 50MG-F OLi OLi OH O acids crepenynic acid, stearolic acid, and tariric acid. LiO P O OH S OH O N OLi H O O 30

Name Structure Cat. No. Name Structure Cat. No.

Methylmalonyl NH2 M1762-1MG Lipoteichoic acid from - L2515-5MG N N O O OH coenzyme A tetralithium H H O O M1762-5MG Staphylococcus aureus L2515-10MG N N N N salt hydrate LiO S O P O P O O CH3 M1762-25MG L2515-25MG CH3 O O H3C OLi OLi

O OH Lipoteichoic acid from - L3265-5MG • xH2O HO P OLi O Bacillus subtilis L3265-25MG Lipid A, monophosphoryl - L6895-1MG from enterica L6895-5MG serotype minnesota Re Malonyl coenzyme A NH2 M4263-5MG 595 (Re mutant) N N lithium salt O O OH M4263-10MG H H O O N Lipid A, monophosphoryl - L6638-1MG N N N HO S O P O P O M4263-25MG CH3 O from F583 L6638-5MG O O H3C OH OH O M4263- (Rd mutant) • xLi HO P O OH OH 100MG Lipid A, diphosphoryl - L0774-1MG

from Salmonella enterica L0774-5MG serotype minnesota Re Lipoteichoic acid from - L3140-5MG 595 (Re mutant) Streptococcus pyogenes L3140-10MG Lipid A, diphosphoryl from - L5399-1MG L3140-25MG Escherichia coli F583 (Rd L5399-5MG mutant) Lipoteichoic acid from - L4015-5MG Streptococcus faecalis L4015-25MG L-NASPA - P0247-1MG P0247-5MG

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