IUPAC-IUB Commission on Biochemical Nomenclature (CBN)
World Wide Web version prepared by G. P. Moss
School of Physical and Chemical Sciences, Queen Mary University of London,
Mile End Road, London, E1 4NS, UK
These Rules are as close as possible to the published version [see Arch. Biochem. Biophys., 1974, 161(2), iii-xi (between pages 334-335); Biochem. J., 1975, 147, 1-10; Biochemistry, 1974, 13, 1555-1560; Eur. J. Biochem., 1974, 45, 7-12; Pure Appl. Chem., 1976, 48, 495-502; Biochemical Nomenclature and Related Documents, 2nd edition, Portland Press, 1992, pages 272-277; Copyright IUPAC and IUBMB; reproduced with the permission of IUPAC and IUBMB]. If you need to cite these rules please quote these references as their source. In setting up the World Wide Web version some errors were detected and appropriate corrections have been made. The changes have been marked by which is a link to details of the change and where it applies. A PDF of the printed version is available.
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Note. In this document the names cobyrinic acid, cobinic acid, cobamic acid, and cobalamin, and names derived from them, imply the relative and absolute configurations shown in the structural formulas. a and b are used as in Steroid Nomenclature (2) and the IUPAC E Rules (3) to indicate stereochemical configuration. Epimers at C-3, C-8, and C-13 may be designated as, e.g., 13-epicobalamin.
1. The corrinoids are a group of compounds containing four reduced pyrrole rings joined into a macrocyclic ring by links between their a positiom; three of these links are formed by a one-carbon unit (methylidyne radicals) and the other by a direct Ca-Ca bond. They include various B-12 vitamins, factors, and derivatives based upon the skeleton of corrin, C19H22N4 (structure I). The atoms are numbered and the rings are lettered as shown in structure I. The numbering is thus the same as that of the porphyrin nucleus, number 20 being omitted to preserve the identity.
Note. The name "corrin" was proposed by those who established its structure because it is the core of the vitamin B-12 molecule; the letters "co" of corrin are not derived from the fact that vitamin B-12 contains cobalt. However, this does not apply to the "cob" terms below, all of which do contain "co" for cobalt.
2. Some important corrinoids that are more unsaturated than corrin itself are derivatives of octadehydrocorrin. This has sometimes been called tetradehydrocorrin because it has four additional double bonds. Although this could be indicated by the prefix "tetrakis(didehydro)," "octadehydro" is preferred.
The octadehydrocorrin system IA has the trivial name corrole.
Note "Pentadehydrocorrin" in the previous document (1) was an error.
3. Many important corrinoids have a regular pattern of substituents on the methylene carbon atoms of the reduced pyrrole rings and a cobalt atom in the center of the macro cyclic ring. The heptacarboxylic acid II is named cobyrinic acid. The carboxyl groups are designated by the locants a to g, as shown in II. Cobyrinic a,b,c,d,e,g-hexaamide, formerly sometimes referred to as Factor V1a, is named cobyric acid. Substituents on the side chains may be designated by appropriate locants, e.g., 7b1-methylcobyrinic acid, if -CH(CH3)CO2H replaces -CH2CO2H at C-7b of cobyrinic acid.
4. The compound III (R = OH, R' = H), which is the amide formed by combination of cobyrinic acid with D-1-amino-2-propanol at position f, is named cobinic acid; its hexaamide (III; R = NH2, R' = H) is named cobinamide.
5. The compound III (R = OH, R' = structure V) in which cobinic acid is further substituted at the 2 position of the aminopropanol by an a-D-ribofuranose 3-phosphate residue (V) is named cobamic acid; its hexaamide (III; R = NH2, R' = V) is named cobamide.
6. Glycosyls and nucleotides (which are N-glycosyl derivatives at C-1 of the ribofuranose unit) of cobamides are named by adding the name of the appropriate aglycon radical (ending in "yl") as a prefix to the name of the corrinoid allotted according to 1-5, e.g., aglyconylcobamide (VI).
7. Most of the important natural products in this series have aglycon radicals containing an imidazole nucleus, one N of the latter being covalently bonded to the ribose while the other is coordinately bonded to what is, by this attachment, defined as the cobalt-a position. The latter situation (VII) is assumed to exist unless otherwise indicated. When another ligand occupies the cobalt-a position, it and its locant may be indicated by, e.g., (Coa-ligand)-aglyconylcobamide (VIII). The absence of a "Coa-ligand" term, as in the cobalamins (see Section 9), indicates that the aglycon radical attached to the ribose occupies the cobalt-a position as well.
8. Cobamides bearing a ligand in the cobalt-b position (which implies Co(III)) may be named as follows:
or, if the aglycon is attached to the cobalt-a position, as indicated in Section 7
In a cobalamin (see Section 9), the latter becomes simply
See also Section 15.
9. Cobalamins. A cobalamin is a cobamide in which 5,6-dimethylbenzimidazole is the aglycon attached by a glycosyl link from its N-1 to the C-1 of the ribose and additionally linked, as stated in Section 7, by a bond between the N-3 and the cobalt (in position a). They may be named as cobamides, as above, or according to the pattern:
(ligand in Cob position, if any)-cobalamin (Xb)
Coa-[a-(5,6-Dimethylbenzimidazolyl)]-Cob-cyanocobamide, also known as vitamin B-12, is termed cyanocobalamin.
Coa-[a-(5,6-Dimethylbenzimidazolyl)]-Cob-aquacobamide, also known as vitamin B-12a, is termed aquacobalamin.
Coa-[a-(5,6-Dimethylbenzimidazolyl)]-Cob-hydroxocobamide, also known as vitamin B-12b, is termed hydroxocobalamin. (Note: aquacobalamin is the conjugate acid of hydroxocobalamin.)
Coa-[a-(5,6-Dimethylbenzimidazolyl)]-Cob-nitritocobamide, also known as vitamin B-12c, is termed nitritocobalamin.
10. Anion(s) associated with the corrinoids is (are) stated in the usual way after the name of the (cationic) corrinoid, e.g., cobamic dichloride (not dichlorocobamic acid).
11. The state of oxidation of the cobalt may be specified, when necessary, as follows:
Note. The previous document (1) erred in prefixing "cyano" to names 2 and 3.
12. Displacement of the ribosyl-bound aglycon base from its normal coordinate bonding to position a of the cobalt by another ligand (or by water) may be indicated by placing the name and locant of the replacing ligand before the corrinoid name and enclosing the modified corrinoid name (see Section 6) in parentheses. (See also Section 7.)
Coa-aqua-Cob-methyl(2-methyladenylcobamide), in which the 2-methyladenyl residue is attached to the ribose residue but is not coordinately bound to the cobalt atom, having been displaced by water. Methyl occupies the Cob position.
13. Modified, derived, or related compounds are named systematically from the largest of the compounds I, II, or III that is contained in them.
cobyrinic acid a,b,c,d,e,g-hexaamide f-2-hydroxyethylamide
3,8,13,17-tetraethyl-1,2,2,5,7,7,12,12,15,17,18-undecamethylcobalticorrin dichloride (for the dichloride of fully decarboxylated cobyrinic acid)
12a1-carboxycobyrinic acid (for cobyrinic acid in which the 12a-methyl group has been replaced by -CH2CO2H)
14. Replacement of the cobalt atom in compounds II or III by another metal or by hydrogen is indicated by replacing "co" in the "cob" part of the name with the name or the root of the name of the replacing metal followed by "o" or "i" according to its valence (e.g., cupri, cupro, zinco). When cobalt is replaced by hydrogen, "hydrogeno" replaces "co."
Examples: ferrobamic acid; hydrogenobamic acid
See Note to Section 1 concerning corrin. This replacement nomenclature does not apply to corrole (Section 2).
15. Cofactor Forms. The coenzymatically active forms of the B-12 vitamins (Section 12) and their analogs possess an organic ligand, either methyl or 5'-deoxy-5'-adenosyl, attached to the b position of the cobalt by a carbon-to-cobalt bond, i.e., in the position of the CN in formula IV. These adducts (4) should be named according to the pattern:
Coa-(radical in a position)-Cob-(ligand in b position)(corrinoid name) or (ligand in b position)cobalamin, if the radical in the a position is dimethylbenzimidazole
Note For brevity, 5'-deoxy-5'-adenosyl may be replaced by adenosyl, with definition, as is commonly seen in S-adenosylmethionine. The intermediate form, 5'-deoxyadenosyl, should not be used.
Coa-[a-(5,6-dimethylbenziniidazoiyl)]-Cob-adenosylcobamide, or adenosylcobalamin, for the compound formerly known as "coenzyme B-12"
Coa-[a-(5,6-dimethylbenzimidazolyl)]-Cob-methylcobamide or methylcobalamin, for the compound involved in several reactions, including methionine biosynthesis, where a methyl group is ligated to the cobalt in the b position
Coa-[a-(7-adenyl)]-Cob-adenosylcobamide, the coenzymatically active form of "pseudovitamin B-12," capable of replacing adenosylcobalamin in many systems.
16. Summary. The trivial names applied to corrinoids of varying complexity are perhaps confusing to the nonspecialist, and it seems desirable to tabulate (in outline) how they are interrelated (Table 1).
|Section||Description||Specific Names, in Increasing Order of Complexity|
|1||Skeleton (porphyrin nucleus minus C-20)||Corrin (I)|
|3||1, with standard side chains and with cobalt||Cobyrinic acid (II)||Cobyric acid|
|4||3, with D-1-amino-2-propanol at position f||Cobinic acid (III)||Cobinamide|
|5||4, with D-ribofuranose 3-phosphate at position 2 of the aminopropanol||Cobamic acid (III-V)||Cobamide|
|7||5, with heterocyclic base attached by N-glycosyl link at position 1 of ribose and attached as an a ligand to cobalt (Sections 6; 7)||Aglyconylcobamide (VI)|
|9||Many "B12" vitamins and derivatives, in which the Cobalamin heterocyclic base is 5,6-dimethylbenzimidazole, are given the trivial name "cobalamin" (Section 9)||Cobalamin|
|15||"B12 coenzymes," compounds in which a further organic group (X-yl) is b-ligated to cobalt (Sections 9, 15)||X-ylcobalamin; (Coa-ligandyl)-|
(1) In formulas II and III, the corrin nucleus is represented as being roughly in the plane of the paper. Bonds joining peripheral substituents to the nucleus are shown by the same convention as in the steroid series (2), i.e., full (heavy) lines are bonds lying above the plane of the ring system, while dashed (broken) lines are bonds lying below this plane.
(2) Formulas II, III, and IV represent the true absolute stereochemical configuration of the structures as determined by X-ray work (5, 6). The CN is in the b position of the cobalt, the ribose-bound heterocyclic base in the a position, in formula IV. When adenine is the heterocyclic base, it is usually bound to the ribose by its N-7, the opposite from what is seen in the nucleic acids.
(3) Formula VIV, it is written with the a-substituent at C-1 above the plane of the ring (i.e., the reverse of the usual carbohydrate method) (7).
(1) IUPAC-IUB (1966), Biochem. J. 102, 19; IUPAC Information Bulletin 26, 19; J. Biol. Chem. 241, 2992; and elsewhere.
(2) IUPAC-IUB (1969), Arch. Biochem. Biophys. 136, 13; Biochemistry 8, 2227; 10, 4994; Biochim. Biophys. Acta 164, 453 (248, 387); Pure Appl. Chem. 31, 283 (1972); and elsewhere. [Now available as the 1989 recommendations on steroids]
(3) IUPAC (1971), Eur. J. Biochem. 18, 151; J. Org. Chem. 35, 2899; Pure Appl. Chem. 45, 11 (1976); and elsewhere. [Available as the 1974 recommendations on stereochemistry; Section E]
(4) L. Ljungdahl, E. Irion, and H. G. Wood (1966), Fed. Proc., Fed. Amer. Soc. Exp. Biol. 25,1642.
(5) D. C. Hodgkin, J. Kamper, J. Lindsey, M. MacKay, J. Pickworth, J. H. Robertson, C. B. Shoemaker, J. E. White, R. J. Prosen, and K. N. Trueblood (1957), Proc. Roy. Soc. Ser. A, 242, 228.
(6) D. C. Hodgkin (1965), Science 150, 979.
(7) IUPAC-IUB (1971), Biochem. J. 125, 673-695; Biochemistry 10, 3983-4004; Biochim. Biophys. Acta 244, 223-302; Eur. J. Biochem. 21, 455-477, 25, 4 (1972); J. Bol. Chem. 247, 613-634 (1972); Tentative Nomenclature Appendix No 7 (Sept 1970) IUPAC Inf.; and elsewhere. [Now available as the 1996 recommendations on carbohydrates]
Appendix: Abbreviations for Corrinoids
This appendix was inspired by the burgeoning literature concerning corrinoid compounds, many of which have long and unwieldy names - a fact that has led to a variety of ad hoc abbreviations that in turn has led to difficulties for the reader.
Many individuals, including but not limited to those whose names appear in the references, have assisted in the development of the system and symbols here proposed. They are not here named, but a special acknowledgment is made of the assistance of B. M. Babior to CBN in the construction of this appendix.
In accordance with several preceding CBN documents (1-3), as well as with standard chemical practice, the abbreviations are constructed by assembling symbols representing the various radicals involved, rather than from combinations of letters drawn haphazardly from the complete names of the compounds. The use of symbols reflects the actual structure of a compound and facilitates the writing of equations for its chemical transformations. In particular, the use of DBC, DMBC, etc., is discouraged, as is the use of B-12 (except as vitamin B-12), coenzyme B-12, and "factor" terms.
I. Names and Symbols
|of free acid||of hexaamide||(for the hexaamide)|
|cobyrinic acid||cobyric acid||Cby|
Note A cobalamin is a cobamide in which 5,6-dimethyibenzimidazole is covalently bonded to the ribose in a-glycosidic linkage; it is thus a dimethylbenzimidazolylcobamide and can be symbolized as such. However, it is often convenient to have a short symbol for this complex, hence Cbl. Cbl is recommended in place of the former B12 or B-12 for chemical use.
II. Designation of Substituents Attached to Cobalt
Ligands coordinated to the a and b position of the cobalt (below and above the plane of the corrin residue, respectively, as shown in structure IV) are represented by terms that precede the symbol for the corrinoid residue. If the positions of the ligands are unknown or not specified, the two terms representing the ligands in the a and b position are enclosed in one set of parentheses and are separated by a comma. If the positions are known and specified, the a ligand is set apart by parentheses; the b is enclosed (separately) only if its complexity may make it ambiguous. If the ligands are identical, a single term followed by the subscript 2 is used.
A. Anion Substituents. The chemical symbol for the anion used. Aqua is abbreviated aq. Examples:
|(Me)aqCbi||(methyl)aquacobinamide (4) (methyl in a position)|
|(CN)MeCbi||(cyano)methylcobinamide (methyl in b position)|
|(CN,aq)Cbi or (aq,CN)Cbi||cyanoaquacobinamide (ligand location unspecified)|
B. Alkyl Substituents.
(1) Primary substituents are designated by naming the alkyl groups without denoting the position attached to the cobalt, as it is always 1. Examples:
Note. Symbols for alkyl groups are Me, Et, Pr, Pri, Bu, Bus, But, Pe, Hx, Hp, ....
(2) Secondary substituents are named similarly, except that the position attached to the cobalt is given by a locant suffixed to the name of the alkyl group (as in the -X-yl name). Examples:
(aq)(Bu-2)Cbi or (aq)BusCbi (aqua)(sec-butyl)cobinamide (5)
(aq)(3-OAcBu-2)Cby (aqua)(3-acetoxybut-2-yl)cobyric acid
(3) Alicyclic groups are indicated by a small "c" before the symbol for the alkyl residue. In these compounds, cobalt is always assumed to be substituted in position 1 of the ring. Examples:
(4) 5'-Deoxy-5'-adenosyl in the b coordination position, as in "coenzyme B-12," is represented by the symbol Ado for "adenosyl"; a 2'-deoxyadenosine residue by dAdo (3). Unusual deoxyadenosyl residues can be indicated by superscripts (e.g., d3Ado, d2,3Ado). See C below.
C. Cobamides of the Cobalamin Type. As the symbol Cbl designates a-(5,6-dimethylbenzimidazolyl)cobamide [cob(III)alamin], only those cobamides having this base utilize Cbl. Those containing another base are named as cobamides, utilizing the symbol Cba. Hence, Cbl is preceded by only a single term, the one representing the b-substituent. Examples are given in Table IA.
|CN-Cbi||Cyanocob(III)alamin (vitamin B-12)|
|AdoCbl||Adenosylcob(III)alamin (6, 7)|
|PrCbl||n-Propylcob(III)alamin; methyl-, etc., similarly (8, 9)|
|(Ade)(Pr-2)Cba or (Ade)Pri-Cbaa||Coa-[a-(Aden-9-yl)]-Cob-isopropylcobamide|
|(5-MeOBza)MeCba||Coa-(5-Methoxybenzimidazolyl)-Cob-methylcobamided (12, 13)|
|(2-MeAde-7)CN-Cbaa||Coa-[a-(2-Methyladen-7-yl)]-Cob-cyanocobamide (11, 14)|
|(Ade)CN-Cbaa||Coa-[a-(Aden-9-yl)]-Cob-cyanocobamide (pseudovitamin B-12)|
|(Ade)OH-Cbaa||Coa-[a-(Aden-9-yl)]-Cob-hydroxocobamide (hydroxopseudovitamin B-12)|
a Ade alone represents adenine bonded to the ribosyl moiety through its 7 position (i.e., a 7-a-D-ribofuranosyladenine). Bonding to the cobalt is thus through N-9. When these positions are reversed, Ade-7 and aden-7yl are used (i.e., the locant specifies the N linked to cobalt).
b Bza = benzimidazolyl.
c As this is a cobalamin, the adenine residue is not in the Coa position, but is attached (-9-yl) to a but-4-yl residue that is in turn linked to the b position of the cobalt. Named as a cobamide, it would be (Me2Bza)[4-(Ade-9)Bu]Cba.
d Factor IIIm (12, 13).
(ii) If the replacing base (in a position) is unspecified, the term (?) is used, e.g., (?)MeCba. The term (OH/base) indicates that the ribose residue is not attached to the Coa-linked base.
(iii) If the a substituent (the "base") is displaced from the cobalt by another ligand, but remains attached to the ribosyl residue, the same system is used. Example:
|(Ade/CN)CN-Cba||Coa-cyano-Cob-cyano(adenylcobamide) or dicyanoadenylcobamide|
In abbreviating cobalamin derivatives, the base need not be specified. Replacement of the base by another Coa ligand is indicated by merely adding to the abbreviation a term corresponding to the replacing ligand. Examples:
|(OH)MeCbl||Coa-hydroxo-Cob-methylcobalamin or Coa-hydroxo-Cob-methyl(dimethylbenzimidazolylcobamide)|
|(CN)2Cbl||Coa-cyano-Cob-cyanocobalamin or dicyanocobalamin|
(iv) Cobalt valences of II or I may be indicated by superscripts (e.g., CblII).
III. Designation of Alterations and Substitutions on the Corrin Ring
Substituents on the ring itself are represented by symbols following the symbol for the corrinoid, with locants indicating the positions of the substituents. Epimerization is indicated in a similar manner. Symbols representing replacements on the carboxyl groups at the periphery of the corrin residue follow those that designate substituents directly on the ring. The location of the substituent is indicated by the letter corresponding to the carboxyl group that carries it. Examples:
|(aq)AdoCbi(e-PhNH)||Coa-aqua-Cob-adenosylcobinic a,b,c,d,g-pentaamide e-anilide|
|(CN)ClCby(8-NH-c-lactam)||Coa-cyano-Cob-chloro-8-aminocobyrinic acid c-lactam|
|(CN)2Cby(OMe)7||dicyanocobyrinic heptamethyl ester (16)|
If the location of the carboxyl substituent(s) is unknown, a term of the following structure should be used:
where a:g indicates a substitution at the periphery of the ring, X is the replacing group, and n refers to the number of carboxyl groups substituted. Examples:
|(CN,aq)Cby[a:g-(NH2)5]||cyanoaquacobyrinic acid pentaamide (17)|
|(CN)2-Cby[10-Cl-a:g-(NH2)5]||10-chloro derivative of the above|
IV. Replacement of Cobalt by Other Metals (18, 19)
Corrinoids containing metals other than cobalt are symbolized by placing the symbol of the replacing metal in square brackets preceding and attached to the symbol of the corrinoid. Thus, a hydrogenocobamide utilizes [H]Cba, a nickelocobalamin [Ni]CblII, a zincocobinamide [Zn]CbiII, etc. Phenylcupribamide (19, 20) could be indicated as (Ph)[Cu]CbaII. I, II, and III may be added as superscripts when needed.
V. Isotopic Labeling
A labeled position is indicated in the usual fashion (21), e.g.
As corrin contains no metal (the name "corrin" being derived from "core," not "cobalt"), complexes of metals with corrin require specification of both terms. Example: CuIICrn for copper(II) corrin.
(1) IUPAC-IUB Commission on Biochemical Nomenclature (1972), Arch. Biochem. Biophys. 150, 1; Biochem. J. 126, 773; Biochemistry 11, 1726; Biochim. Biophys. Acta 263, 205; Eur. J. Biochem. 27, 201; J. Biol. Chem. 247, 977; Pure Appl. Chem. 40, 315 (1974). [Now incorporated in 1983 version of amino acids and protein nomenclature.]
(2) IUPAC-IUB Commission on Biochemical Nomenclature (1972), Arch. Biochem. Biophys. 151, 597-602; Biochem. J. 127, 753-756; Biochemistry 11, 942-944; Biochim. Biophys. Acta 278, 211-217; Biopolymers 11, 321-327; Eur. J. Biochem. 26, 301-304; J. Biol. Chem. 247, 323-325; Pure Appl. Chem. 33, 437-444 (1973).
(3) IUPAC-IUB Commission on Biochemical Nomenclature (1970), Arch. Biochem. Biophys. 145, 425; Biochemistry 9, 4022; Tentative Nomenclature Appendix No 9 (Feb 1971) IUPAC Inf. [Now available on the web]
(4) W. H. Pailes and H. P. C. Hogenkamp (1968), Biochemistry 7, 4160.
(5) J. D. Brodie (1969), Proc. Nat. Acad. Sci. U. S. 62, 461.
(6) B. M. Babior (1969), J. Biol. Chem. 244, 2917.
(7) G. J. Cardinale and R. H. Abeles (1967), Biochim. Biophys. Acta 132, 517.
(8) H. P. C. Hogenkamp, J. E. Rush, and C. A. Swenson (1965), J. Biol. Chem. 240, 3641.
(9) J. Stavrianopoulos and L. Jaenicke (1967), Eur. J. Biochem. 3, 95.
(10) P. Overath, E. R. Stadtman, G. M. Kellerman, and F. Lynen (1962), Biochem. Z. 336, 77.
(11) R. Bonnett (1963), Chem. Rev. 63, 573.
(12) E. Irion and L. Ljungdahl (1968), Biochemistry 7, 2350.
(13) L. Ljungdahl, E. Irion, and H. G. Wood (1966), Fed. Proc., Fed. Amer. Soc. Exp. Biol. 25, 1642.
(14) M. Hayashi and T. Karnikub (1971), FEBS (Fed. Eur. Biochem. Soc.) Lett. 15, 213.
(15) Y. Uchida, M. Hayashi, and T. Kamikubo (1973), Vitamins (Jap.) 47, 27; (1973), Chem. Abstr. 78, 94046e.
(16) L. Wertheman, Dissertation, E.T.H. Zurich, 1968.
(17) K. Bernhauer, H. Vogelmann, and F. Wagner (1968), Z. Physiol. Chem. 349, 1281.
(18) J. I. Toohey (1966), Fed. Proc., Fed. Amer. Soc. Exp. Biol. 25, 1628.
(19) V. B. Koppenhagen and J. J. Pfiffner (1971), J. Biol. Chem. 246, 3075.
(20) V. B. Koppenhagen and J. J. Pfiffner (1970), J. Biol. Chem. 245, 5865.
(21) Instructions to Authors (1973), J. Biol. Chem. 248, 4; and elsewhere.