Biochem. J. (1978) 171, 21-35
`Printed in Great Britain
`
`The Nomenclature of Lipids a
`(Recommendations 1976)b,C
`
`IUPAC-IUB Commission on Biochemical Nomenclatured
`
`CONTENTS
`I. Fatty acids, neutral fats, long-chain alcohols and long-chain bases
`A. Generic terms (Lip-1.1 - 1.5).
`B. Individual compounds .
`1. Fatty acids and alcohols (Lip-1.6 - 1.7) .
`2. Sphinganine and derivatives (Lip-1.8 - 1.11)
`3. Glycerol derivatives (Lip-1.12 - 1.13)
`C. Symbols and abbreviations (Lip-1.14 - 1.18).
`II. Phospholipids.
`A. Generic terms (Lip-2.1 - 2.10)
`B. Individual compounds (Lip-2.11 - 2.12)
`III. Glycolipids.
`A. General considerations
`B. Generic terms (Lip-3.1 - 3.5) .
`C. Individual compounds (Lip-3.6 - 3. 12) .
`D. Symbols and abbreviations (Lip-3.12 - 3.14).
`IV. Neuraminic acid (Lip-4.1 - 4.3).
`Appendix A: names of and symbols for higher fatty acids.
`Appendix B: symbols recommended for various constituents of lipids
`Appendix C: abbreviated representation of gangliosides
`
`21
`
`22
`22
`23
`23
`23
`25
`25
`26
`26
`28
`28
`28
`29
`29
`30
`31
`33
`34
`35
`
`a Documentc of the IUPAC-IUB Commission on
`Biochemical Nomenclature (CBN) approved by IUPAC
`and IUB in 1976, and published with the cooperation of
`the IUB Commission of Editors of Biochemical
`Journalsd. Comments on these Recommendations and
`suggestions for future revisions may be sent to any
`member of CBNd.
`b These Recommendations are a revision and extension
`of "The Nomenclature of Lipids", which appeared in
`1967, as amended in 197011'
`Vol. 171
`
`c Reprints of this document, supplied by the publishing
`journals, may be obtained from W. E. Cohn (Director
`of the NAS-NRC Office of Biochemical Nomenclature),
`Biology Division, Oak Ridge National Laboratory,
`P. O. Box Y, Oak Ridge, Tenn., U.S.A., 37830.
`d Members of CBN are: 0. Hoffmann-Ostenhof (Chair-
`man), W. E. Cohn (Secretary), A. E. Braunstein, H. B. F.
`Dixon, B. L. Horecker, W. B. Jakoby, P. Karlson,
`W. Klyne, C. Liebecq, E. C. Webb.
`
`HYDRITE EXHIBIT 1018
`(1 OF 15)
`
`

`
`22
`
`IUPAC-IUB COMMISSION
`
`In 1967, a "Document for Discussion" on lipid
`nomenclature[11 was issued by CBN. It included
`a special system for the designation of configura-
`tion in glycerol derivatives that deviated con-
`siderably from standard stereochemical nomen-
`clature%. This system is based upon a fixed num-
`bering ("stereo-specific numbering") for glycerol,
`regardless of substituents. It was hopedl[1 that
`"discussion will lead shortly to the formulation"
`of recommendations acceptable to chemists in the
`field of lipids.
`In subsequent years, there has been little discus-
`sion about this principle of stereospecific num-
`bering; it has been well accepted within the field
`of glycerol derivatives, for which it has been
`especially usefule, and is widely used. However,
`during this same period, many new and complex
`lipids and glycolipids have been isolated. Moreover,
`
`the Commissions on the Nomenclature of Organic
`Chemistry (CNOC) and Inorganic Chemistry
`(CNIC) issued, in 1973, "Nomenclature of Or-
`ganic Chemistry, Section D"[21, which includes a
`section on the nomenclature of phosphorus-con-
`taining organic.compounds and necessitates a
`reconsideration of the earlier nomenclature[ I in
`this area.
`The present "Recommendations 1976" are based
`on reports of working groups on lipidsf and
`glycolipidsg. The main features are:
`1. the system of stereospecific numbering is
`retained;
`2. semisystematic nomenclature is extended to
`the plasmalogens;
`3. a semisystematic nomenclature for higher
`glycosphingolipids, based on trivial names for
`specific tri- and tetrasaccharides, is proposed.
`
`RECOMMENDATIONS
`
`I. FATTY ACIDS, NEUTRAL FATS, LONG-CHAIN ALCOHOLS AND LONG-CHAIN BASES
`
`A. Generic terms
`Lip-i. 1. The term fatty acid designates any one
`Lip-1. 2. Neutral fats are mono-, di- or triesters of
`glycerol with fatty acids, and are therefore termed
`of the aliphatic monocarboxylic acids that can
`be liberated by hydrolysis from naturally occur-
`monoacylglycerol, diacylglycerol or triacylgly-
`ring fats and oils. In the terms "free fatty acids"
`cerol, as appropriate. "Acylglycerols" includes
`or "nonesterified fatty acids", now widely in use,
`mixtures of any or all of these.
`"free" and "nonesterified" are actually redundant Comments
`and should be omitted (See Lip-i .14). [The
`i) The term "acyl" is used in Organic Nomenclature[31
`designation "aliphatic carboxylate (C o-C26,
`to denote the radical formed by loss of the OH group
`nonesterified)" used by the Commission on Quan- from the acid function of any acid (cf. Lip-1.6). We are
`tities and Units in Clinical Chemistry is correct,
`concerned here with acyl radicals of aliphatic carboxylic
`but rather cumbersome.] Whenever the sum of
`acids with four or more carbon atoms, the larger members
`fatty acids and their esters is determined by an
`of which (> Clo) are also known as "higher fatty acids."
`analytical method, this should be explicitly
`stated. (See also Lip-i .6).
`
`e CBN does not wish to imply that the idea of stereo-
`specific numbering should be applied to other groups of
`compounds. It is the symmetry of glycerol itself, but
`the asymmetry of its derivatives carrying different
`substituents at 0-1 and 0-3, as well as the unique place
`of these compounds in lipid metabolism, that makes this
`special treatment desirable.
`
`f Members of the Working Group on Lipid Nomenclature
`e-.
`H. Hirschmann (U.S.A.), P. Karlson (Germany; convenor),
`W. Stoffel (Germany), F. Snyder (U.S.A.), S. Veibel
`(Denmark), F. Vogtle (Germany).
`g Members of the Working Group on Glycolipid Nomen-
`clature: S. Basu (U.S.A.), R. 0. Brady (U.S.A),
`R. M. Burton (U. S. A.), R. Caputto (Argentina), S. Gatt
`(Israel), S. I. Hakomori (U.S.A.), M. Philippart (U.S.A.),
`L. Svennerholm (Sweden), D. Shapiro (Israel),
`C. C. Sweeley (U. S. A.), H. Wiegandt (Germany;
`convenor).
`
`1978
`
`HYDRITE EXHIBIT 1018
`(2 OF 15)
`
`

`
`NOMENCLATURE OF LIPIDS
`
`23
`
`ii) The old terms monoglyceride, diglyceride and tri-
`glyceride are discouraged and should progressively be
`abandoned, not only for consistency, but mainly be-
`cause strict interpretation does not convey the intended
`meaning. "Triglyceride", taken literally, indicates three
`glycerol residues (e.g., cardiolipin), diglyceride two (e.g.,
`phosphatidylglycerol), and a monoglyceride is a mono-
`acylglycerol.
`Lip-1.3. The generic term "long-chain alcohol"
`or "fatty alcohol" refers to an aliphatic compound
`with a chain-length greater than C10 that possesses
`a terminal CH2OH group. Such alcohols should be
`named according to systematic nomenclature13 .
`(See Lip- 1.7).
`Lip-1.4. The term sphingoid or sphingoid base
`refers to sphinganine (cf. Lip-1.8), [D-erythro-2-
`amino- ,3-octadecanediol (I)], its homologs and
`stereoisomers (II, III), and to the hydroxy and
`unsaturated derivatives of these compounds
`(IV - VI). The term "long-chain base" may be
`used in a wider sense to indicate any base con-
`taining a long-chain aliphatic radical.
`Lip-1.5. The following generic terms are used for
`the following groups of compounds:
`a) sphingolipid, for any lipid containing a
`sphingoid;
`b) ceramide, for anN-acylated sphingoid;
`c) sphingomyelin, for a ceramide-l-phospho-
`choline (see ref.[21 for this use of "phospho";
`also Lip-2.1 1);
`d) glycosphingolipid, for any lipid containing a
`sphingoid and one or more sugars. (See sec-
`tions I, B, 2 and II, A for other generic terms).
`
`B. Individual compounds
`1. Fatty acids and alcohols
`Lip-1.6. Fatty acids (cf. Lip-1.1) and their acyl
`radicals (cf. Lip-1.2, comment i) are named ac-
`cording to the IUPAC Rules for the Nomenclature
`of Organic Chemistry (ref.[31, Rule C4). (A list
`of trivial names is given in Appendix A.) Fatty
`acids are numbered with the carbon atom of the
`carboxyl group as C-1. By standard biochemical
`convention, the ending -ate in, e.g., palmitate
`denotes any mixture of the free acid and its ion-
`ized form in which the cations are not specified.
`The ending -ate is also used to designate esters,
`Vol. 171
`
`e.g., cholesteryl palmitate, ethylidene dilaurate,
`etc. (cf. Lip-1 .12). Structural isomers of poly-
`unsaturated acids, hitherto distinguished by Greek
`letters (e.g., ca- and 'y-linolenic acids), are better
`distinguished by the locants of the unsaturated
`linkages (e.g., (9,12,15)- and (6,9,12)-linolenic
`acids, respectively). (See Lip-1.15). However, the
`Greek letter prefixes may be useful in (defined)
`abbreviations (see Appendix A).
`Lip-i. 7. Long-chain alcohols (fatty alcohols) and
`the radicals derived from them should be desig-
`nated by their systematic names (ref.131, Rules
`C-201 and A-I et seq.), but not by trivial names
`that are derived from those of fatty acids.
`Examples: 1-hexadecanol and hexadecyl-, not palmityl
`alcohol and palmityl-; 1-dodecanol and dodecyl-, not
`lauryl alcohol and lauryl-.
`
`2. Sphinganine and derivatives
`Lip-.8. The compound previously known as
`dihydrosphingosine [2D-amino-1,3D-octadecane-
`diol or D-erythro-2-amino-1,3-octadecanediol or
`(2S, 3R)-2-amino-1 ,3-octadecanediol] is called
`sphinganine (I).
`Lip-i. 9. Trival names of higher or lower homol-
`ogs of sphinganine may be derived by adding a
`prefix (ref.[31, Rule A-1) denoting the total num-
`ber of carbon atoms in the main chain of the
`homolog, e.g., icosasphinganine* for the C20
`compound (III), hexadecasphinganine for the C16
`compound.
`Lip-i.10. Affixes denoting substitution of sphin-
`ganine (hydroxy, oxo, methyl, etc.) are used as
`usual, according to existing rules[31. The configu-
`rations of additional substituents should be
`specified by the prefixes "D" or "L " (italic
`capitals, cf. ref.[41) following the locant of sub-
`stitution. These prefixes refer to the orientation
`of the functional groups to the right or left,
`respectively, of the carbon chain when written
`vertically in a Fischer projection with C-I at the
`top (cf. Formulae I - VI). If the configuration is
`unknown, the prefix "X" may be used. In the
`case of a racemic mixture, rac should be used as
`a prefix to the name.
`
`* Formerly eicosasphinganine (see footnote d in
`Appendix A).
`
`HYDRITE EXHIBIT 1018
`(3 OF 15)
`
`

`
`24
`
`CH,OH
`H-C--- NH,
`H-C-OH
`[CH,l,3
`CH3
`
`I
`
`CH,OH
`H,N-C-H
`H-C-OH
`(CHI,l31
`C/I3
`
`II
`
`Sphinganine
`D-erythro or 2S,3R
`configuration implied]
`
`(2R,3R)- (or D-threo-)
`2-Amino-1 ,3-octa-
`decanediol
`
`CH20H
`LWOI
`H-C-N/NH
`
`H-C-OH
`(CH11,6
`C/I
`
`111
`Icosasphinganine*
`
`CH,OH
`
`#H C-NH2
`
`H-C-OH
`
`C-#II
`H-C
`IC/I,?],?
`CI,
`
`V
`
`C/IOH
`
`H-C-NH2
`
`H-C-OH
`
`H-C-OH
`
`C/I
`
`IV
`
`4D-Hydroxysphinganine;
`(2S,3S,4R)-2-amino-
`1,3,4-octadecanetriol;
`(phytosphingosine).
`
`C/I20H
`
`H-C-N/,Y
`
`H-C-OH
`
`C-H
`
`C-H
`ICH/I3
`CH3
`
`VI
`
`Sphingosine;
`trans-4-sphingenine;
`(4E)-sphingenine;
`(2S,3R,4E)-2-amino-4-
`octadecene- ,3-diol.
`
`cis-4-Sphingenine;
`(4Z)-sphingenine.
`
`* Formerly eicosasphinganine (see footnote d in
`Appendix A).
`
`IUPAC-IUB COMMISSION
`
`Sphingoids differing from sphinganine in their
`configurations at C-2 and/or C-3 should not be
`named as derivatives of sphinganine, but with
`fully systematic nameS31, using the prefixes
`D-threo, L-erythro, as appropriate, e.g., D-threo-
`2-amino-I,3-octadecanediol, or (2R, 3R)-2-amino-
`1,3-octadecanediol, for II (cf. Rule Carb-8 in
`ref.s5I). (cf. Lip-1.11, ex. 4).
`Comment. The semisystematic names for the sphingoids
`are significantly shorter than the fully systematic names
`only if the terms chosen imply not only substituents but
`also configurations. Therefore, the name "sphinganine"
`specifies the D-erythro configuration, and it is logical
`that the names of stereoisomers of sphinganine differing
`in configuration at C-2 and/or C-3 should not include
`"sphinganine" as a root. (This recommendation differs
`from that in the previous documentl1 1.)
`The configurations usually encountered have identical
`configurational prefixes only if a DIL but not if the RIS
`system[61 is used; e.g., C-3 is D and R in icosasphinganine
`(III) and D and S in 4D-hydroxysphinganine (IV). When-
`ever it is desirable to use the RIS system, the fully sys-
`tematic name should be used with the specification of
`configuration at every center (and, when applicable, of
`the configuration at the double bond).
`Examples:
`(2R,3R)-2-amino-1,3-octadecanediol, for II;
`(2S,3S,4R)-2-amino-1 ,3,4-octadecanetriol for IV;
`(2S,3R,4E)-2-amino-4-octadecene-1,3-diol for sphin-
`gosine (V). (See also Lip-1.1 1.)
`Lip-. 11. Names for unsaturated compounds are
`derived from the names of the corresponding
`saturated compounds by the appropriate infixes,
`namely ene, diene, yne, etc.'3]. If the geometry
`of the double bond is known, it should be indi-
`cated by the more modern E/Z system (Cf.'6l,
`Rule E-2.2), e.g., (4E)-sphingenine for sphin-
`gosine (V).
`The trivial name sphingosine (V) is retained. If
`trivial names other than sphingosine are used, they
`should be defined in each paper in terms of this
`nomenclature, or of the general nomenclature of
`organic chemistry'3].
`Other names for the substances described in Lip-1.10
`and Lip-1.1:
`4D-hydroxysphinganine for IV, formerly known as
`phytosphingosine;
`(4E)-sphingenine for sphingosine (V);
`(4Z)-sphingenine for the geometric isomer of sphin-
`gosine (VI);
`D-threo-2-amino-1 ,3-octadecanediol for-the C-2 epimer
`of sphinganine (II); cf. Lip-1.10, Ex. 1.
`
`1978
`
`HYDRITE EXHIBIT 1018
`(4 OF 15)
`
`

`
`NOMENCLATURE OF LIPIDS
`
`25
`
`3. Glycerol derivatives
`Lip-i. 12. Esters, ethers and other 0-derivatives
`of glycerol are designated according to Rule
`Carb-1 5 of the Rules of Carbohydrate Nomen-
`clature[SI i.e. by a prefix, denoting the substituent,
`preceded by a locant. If the substitution is on a
`carbon atom, the compound is designated by its
`systematic name and not as a derivative ofglycerol
`(e.g., 1,2,3-nonadecanetriol for C16H33CHOH-
`CHOH-CH20H, which could be considered as
`1-C-hexadecylglycerol). It is permissible to omit
`the locant "O" if the substitution is on the oxy-
`gen atoms of glycerol.
`
`Examples: tristearoylglycerol or tri-O-stearoylglycerol or
`glycerol tristearate, or glyceryl tristearate;
`1,3-benzylideneglycerol or 1,3-0-benzylideneglycerol;
`glycerol 2-phosphate (a permissible alternative to this
`term is 2-phosphoglycerol).
`
`Comment. The alternative system set forth in Rule
`Carb-16 of the Rules on Carbohydrate Nomenclaturel5,
`i.e. the use of the suffix -ate, is less suitable for glycerol
`esters, with the exception of the phosphates (see Exam-
`ples). However, this system may be used to designate
`esters of monofunctional alcohols, e.g. cholesteryl
`palmitate (cf. Lip-1.6).
`Lip-1.13. Stereospecific numbering. In order to
`designate the configuration of glycerol derivatives,
`the carbon atoms of glycerol are numbered stereo-
`specifically. The carbon atom that appears on top
`in that Fischer projection that shows a vertical
`carbon chain with the hydroxyl group at carbon-2
`to the left is designated as C-1. To differentiate
`such numbering from conventional numbering
`conveying no steric information, the prefix "sn"
`(for stereospecifically numbered) is used. This
`term is printed in lower-case italics, even at the
`beginning of a sentence, immediately preceding
`the glycerol term, from which it is separated by
`a hyphen. The prefix "rac- "(for racemo) precedes
`the full name if the product is an equal mixture
`of both antipodes; the prefix "X-" may be used
`when the configuration of the compound is either
`unknown or unspecified (cf. Lip-i.10).
`
`Examples:
`sn-glycerol 3-phosphate for the stereoisomer
`VIII), previously known as either L-o-glycero-
`(VII
`phosphoric acid or as D-glycerol i-phosphate;
`rac-1-hexadecylglycerol;
`1,2-dipalmitoyl-3-stearoyl-X-glycerol.
`
`Vol. 171
`
`Comments
`i) The problem of distinguishing between stereoisomers
`was discussed in extenso in the 1967 document[1 1. In
`brief, difficulties arise because glycerol is a prochiral
`compound. The parent substance of many phospholipids,
`natural glycerol phosphate, has been named both as L-ot-
`glycerol phosphate'7' (VII) and, according to standard
`rules of nomenclature, D-glycerol 1-phosphate'81 (VIII).
`When the RIS system (sequence rule) is applied, substitu-
`tion of one of the primary hydroxyl groups often leads
`to changes in the configurational prefix, thus obscuring
`chemical and biogenetical relationships; it is generally
`inapplicable to the steric description of such mixtures
`as occur in triacylglycerols isolated from natural sources:
`The stereospecific numbering of glycerol and its deriva-
`tives as proposed by Hirschmannl9l, described above
`(and in ref.l l1), avoids these difficulties; it has proved
`useful and is widely accepted.
`ii) The enantiomer of sn-glycerol 3-phosphate (VII) is
`sn-glycerol 1-phosphate (IX), as is evident from the
`structures.
`
`CH20H
`
`CH2OPO3H2
`
`HO-C-H
`
`- H-C-OH
`
`CHOPO3H2
`
`CH2OH
`
`VII
`
`-
`
`Vill
`
`iCH2OPO3H2
`HG-C--H
`
`CH2OH
`
`lx
`
`sn-Glycerol 3-phosphate
`IL-(glycerol 3-phosphate)
`-D-(glycerol 1-phosphate)I
`
`sn-Glycerol 1-phosphate
`[L-(glycerol 1-phosphate)
`D-(glycerol 3-phosphate)I
`
`C. Symbols and abbreviations
`Lip-1.14. The term "fatty acids" (cf. Lip-i.1)
`should not be abbreviated. The use of abbrevia-
`tions like "FFA" for "free fatty acids" or "NEFA"
`for "non-esterified fatty acids" is strongly
`discouraged.
`Comment. The words "acids" and "esters" serve to
`distinguish the "free" (nonesterified) and "bound"
`(esterified) fatty acids, and are as short as or shorter than
`the abbreviations themselves.
`Lip-i. 15. In tables and discussions where various
`fatty acids are involved, the notation giving the
`number of carbon atoms and of double bonds
`(separated by a-colon) is acceptable, e.g. 16: 0 for
`palmitic acid, 18: 1 for oleic acid. Also, terms
`such as "(18:0) acyl" may be used to symbolize
`radicals of fatty acids. (See Appendix A).
`
`HYDRITE EXHIBIT 1018
`(5 OF 15)
`
`

`
`26
`
`IUPAC-IUB COMMISSION
`
`Comment. This system is already widely used. It should,
`however, be kept in mind that it sometimes does not
`completely specify the fatty acid. For example, ao-lino-
`lenic acid and -y-linolenic acid are both 18: 3 acids; the
`designation 18: 3 is therefore ambiguous. In such a case,
`the position of double bonds should be indicated, e.g.
`18: 3(9,12,15) for (9,12,15)-linolenic acid, formerly
`known as a-linolenic acid.
`Lip-1.16. It is sometimes desirable (for example,
`in discussing the biosynthesis of lipids) to indi-
`cate the position of each double bond with
`reference not to the carboxyl group (always C-1),
`but to the end of the chain remote from the
`carboxyl. If n is the number of carbon atoms in
`the chain (i.e., the locant of the terminal methyl
`group) and x is the (lower) locant of the double
`bond, the position of the double bond may be
`defined as (n minus x). Thus, the common posi-
`tion of the double bond in oleic and nervonic
`acids may be given as 18 - 9 and 24 - 9, respec-
`
`tively. This structural regularity should not be
`expressed as c9.
`Lip-i.17. The system described in Lip-i.15 may
`also be used to denote alcohols and aldehydes
`related to fatty acids, provided that the nature of
`the residue is clearly indicated either by the ap-
`propriate name of the compound(s) [e.g. (18: i)-
`alcohol] or in the heading of the table. The I-ene
`of alk-I-en-i-yl (i.e., l-alkenyl) compounds is not
`counted in this system (see Lip-2.1O, comment).
`
`Lip-i. 18. For many complex lipids, a represen-
`tation of the structures using symbols rather than
`structural formulae may be useful. Symbols pro-
`posed for various constituents are given in Ap-
`pendix B (see also ref.l'01), and, for glycolipids, in
`Lip-3. 13. They are constructed in analogy to
`those in use for amino acidsl[", nucleosidesl[21
`and saccharides1'3].
`
`II. PHOSPHOLIPIDS
`
`A. Generic terms
`The Rules ofThe Nomenclature ofOrganic Phos-
`phorus Compounds (also known as D-Rules)[21
`recognize, for biochemical usage, the prefix
`phospho- as an alternate to O-phosphono- (or
`N-phosphono). By a similar convention[IO], -phos-
`pho- may be used as an infix to designate the
`phosphodiester bridge present in such compounds
`as glycerophosphocholine. The use of root names
`like "phosphatidic acid" is retained and extended
`(Lip-2.3 - 2.4).
`Lip-2. 1. Phospholipid may be used for any lipid
`containing phosphoric acid as mono- or diester.
`Likewise, lipids containing C-phosphono groups
`(e.g. compound X) may be termed "phosphono-
`lipids."
`Lip-22. Glycerophospholipid signifies any deriv-
`ative of glycerophosphoric acid that contains at
`least one O-acyl, or O-alkyl, or O-(i-alkenyl)
`group attached to the glycerol residue. Generic
`names for other classes of phospholipids may be
`coined according to this scheme, e.g., sphingo-
`phospholipid, inositolphospholipid.
`
`Comment. The old terms, "phosphatide," "phospho-
`glyeride," and "phosphoinositide" are no longer recom-
`mended because they do not convey the intended
`meaning (see also Lip-1.2).
`Lip-2.3. Phosphatidic acid signifies a derivative
`of a glycerol phosphate (glycerophosphate) in
`which both remaining hydroxyl groups of glycerol
`are esterified with fatty acids. The position of
`the phosphate group may be emphasized by
`stereospecific numbering.
`Comment. For the most common (3-sn)-phosphatidic
`acid and its derivatives, the locants are often omitted.
`However, "phosphatidyl" without locants can lead to
`
`C/120-COR
`
`R'CO-O--C-H-/ o
`11
`CH2O-P-ICH2J2-NH2
`
`OH
`
`x
`A phosphonolipid
`
`CH2O-COR
`H203P-O- C-.H
`CH2O-COR'
`
`XI
`
`2-Phosphatidic acid
`
`1978
`
`HYDRITE EXHIBIT 1018
`(6 OF 15)
`
`

`
`NOMENCLATURE OF LIPIDS
`
`27
`
`ambiguities. It is therefore preferable to use the proper
`locants, for example, 2-phosphatidic acid for compound
`XI, and 3-sn-phosphatidylserine for XIIa.
`Lip-2.4. The common glycerophospholipids are
`named as derivatives of phosphatidic acid, e.g.
`3-sn-phosphatidylcholine (this term is preferred
`to the trivial name, lecithin; the systematic name
`is 1 ,2-diacyl-sn-glycero-3-phosphocholine); 3-sn-
`phosphatidylserine; I-phosphatidylinositol (see
`comment ii below); 1,3-bis(3-sn-phosphatidyl)-
`glycerol.
`
`CH,O0 -COR
`
`NZH
`RX-O-C-H 0
`CH2O-P-O-CH2-CH-COH
`OH
`
`XII a
`
`Phosphatidylserine (3-sn-phosphatidylserine)
`
`CH2O-COR
`HO-C-H 0
`NH2
`CH0-P-O-CH2-CH-CO2H
`OH
`
`XIIb
`
`A 2-lysophospholipid
`
`Comments
`i) It is understood that, in combination with compounds
`like ethanolamine (properly, 2-aminoethanol) or serine,
`which bear both hydroxyl and amino groups, substitu-
`tion by phosphorus is at the hydroxyl group of the
`ethanolamine or serine. Substitution at any other posi-
`tion, or where confusion may arise, requires a locant.
`ii) The phosphorylated derivatives of 1-(3-sn-phospha-
`tidyl)inositol should be called 1-phosphatidylinositol
`4-phosphate and 1-phosphatidylinositol 3,4-bisphos-
`phate, respectively. The use of "diphosphoinositide"
`and "triphosphoinositide" for these is discouraged, as
`these names do not convey the chemical structures of
`the compounds and can be misleading. (Cf. also Table IV
`in ref.I101).
`Lip-2.5. As an alternative, generic names may be
`coined according to Lip-i .13, i.e. using glycerol
`phosphate (glycerophosphate) as the stem. In this
`case, the stereospecific numbering of glycerol
`
`Vol. 171
`
`should be used to indicate the position of the
`phosphoric residue as well as the other substi-
`tuents (acyl-, alkyl-, 1-alkenyl). If the nature of
`these substituents cannot be specified, the prefix
`"radyl" may be used.
`Lip-2.6. Derivatives of phosphatidic acids re-
`sulting from hydrolytic removal of one of the
`two acyl groups may be designated by the old
`prefix lyso e.g. lysophosphatidylethanolamine for
`compound XIIb. A locant may be added to des-
`ignate the site of (hydro)lysis, 2-lyso designating
`hydrolysis at position 2, leaving a free hydroxyl
`group at this carbon atom.
`Comment. The "lyso" terms originated from the fact
`that these compounds are hemolytic. It is here redefined
`to indicate a limited hydrolysis of the phosphatidyl
`derivative (i.e., "deacyl").
`Lip-2. 7. The term plasmalogen may be used as a
`generic term for glycerophospholipids in which
`the glycerol moiety bears an I-alkenyl ether group.
`Lip-2. & The term plasmenic acid signifies a de-
`rivative of sn-glycero-3-phosphate in which
`carbon-I bears an 0-(i -alkenyl) residue, and
`position 2 is esterified with a fatty acid (XIII).
`This term can also be used to name derivatives,
`e.g. plasmenylethanolamine.
`Comments
`i) The use of "phosphatidyl" as a name for the acyl
`radical of phosphatidic acid has facilitated the nomen-
`clature of its various compounds (see Lip-2.4). Therefore,
`it seems logical to offer a similar short term for XIII,
`i.e., "plasmenic acid," as an alternative to the more sys-
`tematic name, 2-acyl-1-alkenyl-sn-glycerol 3-phosphate,
`which, of course, may be used if desired. "Plasmenic"
`is a contraction of "plasmalogenic", and may be especial-
`ly useful in naming derivatives, e.g., plasmenylserine.
`ii) Isomers like those bearing the phosphate residue in
`position 2 (e.g. compound XIV) should not be named
`in this way but as derivatives of the corresponding
`glycerophosphate, using stereospecific numbering.
`
`Cl,O-CH=CHR
`R'C-O-.- c-H
`
`CNHO-P03H2
`
`xIII
`
`A plasmenic acid
`
`CH2O-CH=CHR
`H203P-O=-C--NH
`
`CH20-COR'
`
`A7V
`
`3-Acyl-l-(l-alkenyl)-
`sn-glycerol 2-phosphate
`
`HYDRITE EXHIBIT 1018
`(7 OF 15)
`
`

`
`28
`
`IUPAC-IUB COMMISSION
`
`Lip-2. 9. The term lysoplasmenic acid may be
`used for a derivative of sn-glycero-3-phosphate
`that has an O-(l-alkenyl) residue on carbon-i, the
`hydroxyl group in position 2 being unsubstituted
`(XVa). This name may also be used in combina-
`tions like "lysoplasmenylethanolamine" (XVb).
`
`CH2O-CH=CHR
`HO-C-NH 0
`CH2O-P-OR'
`
`OH
`xv
`XVa: (R' = H):
`a lysoplasmenic acid
`XVb: (R' = CH2CH2NH2)
`a lysoplasmenylethanolamine
`
`CH2O-CH2 - CH2R
`RCO-O-C--H
`
`CH20- P03H?
`XvI
`A plasmanic acid
`
`palmitoleic acid). In such cases, the proper term "al-
`kenyl", if used without the ene locant(s), would be
`misleading. (See Lip-1.17).
`
`B. Individual compounds
`Lip-2.11. Individual glycerophospholipids in
`which the substituents can be specified are named
`according to existing Rules'2'3'5'61, using the in-
`fix -phospho-[2' IO to indicate the phosphodiester
`bridge.
`Example: 2-Palmitoyl-l-stearoyl-sn-glycero-3-phospho-
`ethanolamine for compound XVII.
`
`CH2O-COCn,Hx
`
`C,5Hj,C-O-D-C...H o
`
`CHO-P-O-CH2-CH2-NH2
`
`OH
`
`Lip-2.10. For compounds of type XVI, bearing a
`saturated ether group in position 1 and an acyl
`group in position 2 of sn-glycero-3-phosphate, the
`term plasmanic acid is proposed. Compounds
`deacylated in position 2, or with a substituent on
`the phosphoric residue, can be treated as are the
`plasmenic acids (Lip-2.9).
`Comment. The proposed names will be especially useful
`for naming phosphoric diesters (phosphodiesters), such
`as e.g. plasmanylethanolamine, instead of 2-acyl-1-alkyl-
`sn-glycero-3-phosphoethanolamine. The terms "plas-
`manic acid" and "plasmanyl" may also be applied to
`ethers with an alkyl group bearing a double bond within
`the chain, e.g. a 9-hexadecenyl residue (derived from
`
`XVii
`2-Palmitoyl-1-stearoyl-sn-glycero-3-phosphoethanolamine
`
`Lip-2.12. The ketone derived from glycerol,
`1,3-dihydroxy-2-propanone, also known as dihy-
`droxyacetone, may be termed "glycerone", if
`desired. The name is a contraction of "glycero-
`ketone", and may be useful to emphasize the
`relationship with glycerol, glyceraldehyde (gly-
`ceral), and glycerate. It also permits a simple
`symbolism (Appendix B) and the naming of
`derived lipids, e.g., 1-palmitoyl-3-phosphogly-
`cerone.
`
`III. GLYCOLIPIDS
`
`A. General considerations
`
`Glycolipids (a contraction of glycosyllipids) are
`generally named as glycosyl derivatives of the
`corresponding lipid, e.g., diacylgalactosylgly-
`cerol, glucosylceramide. Because of the heteroge-
`neity of the fatty acids and long-chain bases en-
`countered in most cases, a generic name for the
`lipid moiety is needed, i.e. ceramide. With higher
`
`glycosphingolipids, especially the gangliosides,
`naming problems arise from the complexity of
`the carbohydrate moiety of these compounds.
`The systematic names of the oligosaccharides
`linked to ceramide are so cumbersome that they are
`of the same practical value as, e.g., the systematic
`name for a peptide hormone such as insulin. It
`was felt that this difficulty could be overcome
`only by creating suitable trivial names for some
`
`1978
`
`HYDRITE EXHIBIT 1018
`(8 OF 15)
`
`

`
`NOMENCLATURE OF LIPIDS
`
`29
`
`parent oligosaccharides. In constructing these
`names (see Table I) the following principles were
`observed:
`1. The number of monosaccharide units in an
`oligosaccharide is indicated by the suffixes -biose,
`-triaose, -tetraose, etc. This follows the well-es-
`tablished practice in the carbohydrate field (cf.
`cellobiose, cellotetraose, maltotetraose, etc.),
`with the exception that the suffix -triose, as used
`in maltotriose, has been changed to triaose to
`avoid confusion with the monosaccharides called
`trioses.
`2. The oligosaccharides are grouped in series ac-
`cording to their structure and biogenetic rela-
`tionship.
`3. Differences in linkage (e.g., 1 - 4 versus 1 -+3)
`in otherwise identical sequences are indicated by
`iso- or neo-, used as a prefix.
`On the basis of these names, the semisystematic
`nomenclature for neutral glycosphingolipids and
`gangliosides described below is recommended. A
`set of symbols has been devised that allows a
`simple representation of complex neutral and
`acidic glycosphingolipids (Table I).
`
`B. Generic terms
`Lip-3.1. The term glycolipid designates any com-
`pound containing one or more monosaccharide
`residues linked by a glycosyl linkage to a lipid
`part (e.g., a mono- or diacylglycerol, ajlong-chain
`base (sphingoid) like sphingosine, or a ceramide).
`Lip-3.2. The term glycoglycerolipid may be
`used to designate glycolipids containing one or
`more glycerol residues.
`Lip-3.3. The term glycosphingolipid, as hitherto,
`includes all compounds containing at least one
`monosaccharide and a sphingoid. The glycosphin-
`golipids can be subdivided as follows:
`Neutral glycosphingolipids:
`monoglycosyl- and oligoglycosylsphingoids;
`monoglycosyl- and oligoglycosylceramides.
`Acidic glycosphingolipids:
`sialosylglycosylsphingolipids (gangliosides);
`sulfoglycosylsphingolipids (formerly "sulfatides",
`which is not recommended) (cf Lip-3.1 1).
`Lip-3.4. Psychosine may be used as a generic
`name for l-monoglycosylsphingoids, although
`
`Vol. 171
`
`the latter is preferred. The nature of the monosac-
`charide and the sphingoid is not specified in this
`name.
`Lip-3.5. The term fucolipid may be used to des-
`ignate fucose-containing neutral or acid glycolipids.
`
`C. Individual compounds*
`Lip-3. 6. Glycoglycerolipids may be named either
`as glycosyl compounds according to Rule Carb-24
`or as glycosides according to Rule Carb-23151.
`Example: compound XVIII may be named either 1,2-
`diacyl-3-,B-D-galactosyl-sn-glycerol or 1,2-diacyl-sn-gly-
`cerol 3-3-D-galactoside.
`
`CH2O-COR
`RVW-O.-C-H
`
`HOC/IC20
`
`00
`OH
`
`XVII
`
`Comment. The first form is preferred, as the glycosphin-
`golipids are also named this way.
`Lip-3. 7. A glycosphingolipid is generally named
`-as a glycosylsphingoid or a glycosylceramide,
`'using the appropriate trivial name of the mono-
`or oligosaccharide residue for "glycosyl." It is
`understood that the sugar residue is attached to
`the C-I hydroxyl group of the ceramide. For
`glycosphingolipids carrying two to four saccharide
`residues, the trivial names listed in Table I are
`recommended.
`Comment. It is strongly recommended that the name of
`the oligosaccharide be defined in each publication by
`means of the standard symbols for sugars (as in Table I,
`column 1) rather than by the full name, which is often
`so long as to be confusing.
`Lip-3.8. The trivial name cerebroside designates
`1-,B-glycosylceramide (the natures of the sphingoid
`and of the fatty acid are not specified in this
`name).
`
`* "Individual" in this section refers to the
`carbohydrate moiety only.
`
`HYDRITE EXHIBIT 1018
`(9 OF 15)
`
`

`
`30
`
`IUPAC-IUB COMMISSION
`
`Lip-3.9. Glycosphingolipids carrying fucose ei-
`D. Symbols and abbreviations
`ther as a branch or at the end of an oligohexosyl-
`Lip-
`cip3.13. Simple or complex glycosphingolipids
`ceramide are named as "fucosyl(X)osylceramide"
`can berepresenedaccordiNgutexti
`where (X) stands for the root name of the oligosac-
`rues
`charide. The location of the fiicosyl residue is uIn- s
`t.-
`pendix B), together with the recommended[
`dicated by a Roman numeral designating the posi-
`symbols for the hexoses (Glc, Gal, etc.).
`tion of the monosaccharide residue in the parent
`Examples are given above, and in Table I and
`oligosaccharide (counting from the ceramide end)
`to which the fucose residue is attached, with an
`Appendix C.
`Arabic numeral superscript indicating the position
`within that residue to which the fucose is attached.
`If necessary, the anomeric symbol can be used as
`usual, i.e., preceding "fucosyl-."
`
`Examples for Lip-3.7 and Lip-3.9 (structures given in
`the symbols of Lip-3.13):*
`lactosylceramide for Gal(pl1-4)GlcCer;
`mucotriaosylceramide for Gal(p1-4)Gal(P1-4)GlcCer;
`1112-_e-fucosylisoglobotriaosylceramide for
`Fuc(cl-+2)-Gal(ol-+3)Gal(p1-4),Glc(pl-I)Cer
`Lip-3. 10. Sialoglycosphingolipids (synonym:
`gangliosides) ar