BIOCHIMICA ET BIOPHYSICA ACTA 1

IUPAC-IUB Commiss ion on Biochemical Nomenclature (CBN) Nomenclature for Vitamins B6 and Related Compounds*t

Tentative Rules

I N T R O D U C T I O N

The first n a t u r a l l y occurr ing fo rm of v i t a m i n B~ was isola ted in 1938. I t h a s t he s t ruc tu re , con- f i rmed by chemica l syn the s i s (1939), of 3 -hydroxy- 4,5 - b i s ( h y d r o x y m e t h y l ) - 2 - m e t h y l p y r i d i n e (I; R = - C H 2 O H ). The t r iv ia l n a m e ' py r idox ine ' , p roposed for th i s c o m p o u n d by P. Gy6rgy , c ame in to genera l use as a s y n o n y m for ' v i t a m i n B6'. Two o the r n a t u r a l c o m p o u n d s possess ing v i t a m i n B~ ac t iv i ty , de tec ted in 1944 a n d recognized as t he a ldehyde , or 4- formyl ana logue (I; R = - C H O ) of pyr idoxine , a n d t h e cor respond ing amine , or 4 - a m i n o m e t h y l ana logue (I ; R = -CH2NH2) , were des igna t ed ' py r idoxa l ' a n d ' p y r i d o x a m i n e ' respec- t ively .

W i t h i n t he n e x t few years , I. C. Gunsa lus , E. E. Snell, A. E. B r a u n s t c i n a n d o the rs d e m o n s t r a t e d t h a t a p h o s p h o r y l a t e d de r iva t ive of pyr idoxal , la ter ident i f ied as py r idoxa l 5 ' - p h o s p h a t e ( I I ; R = CHO), is t he coenzyme of a large g roup of specific e n z y m e s ca t a lys ing reac t ions of a m i n o group t ransfe r , deca rboxy la t i on a n d o the r m e t a - bolic t r a n s f o r m a t i o n s of ind iv idua l ami no acids. I n t he course of enzymic t r a n s a m i n a t i o n , py r idoxa l 5 ' - phospha t e undergoes reversible convers ion in to p y r i d o x a m i n e 5 ' - p h o s p h a t e ( I I ; R = - C H ~ N H 2 ) , wh ich ha s coenzyme ac t iv i ty for t h e a m i n o t r a n s - ferases (EC 2 . 6 . 1 . - ) , b u t n o t for o the r t ypes of v i t a m i n B6-dependen t e n z y m e s (2, 3).

I n t he I U P A C Definitive Rules for the Nomen- clature of Vitamins, pub l i shed in 1960 (4), t he t e r m ' py r idox ine ' was r e c o m m e n d e d as a gener ic

* This document is an extension {with minor revision) of Section M-7 of the earlier IUPAC-IUB Tentative Rules, Trivial Names of Miscellaneous Compounds of Importance in Biochemistry (1).

Document of the IUPAC-IUB Commission o n Biochemical Nomenclature (CBN), approved by IUPAC and IUB in 1970 and published by permission of IUPAC and IUB. Comments on and suggestions for future revisions of these tentative rules may be s e n t t o any member of CBN: O. Hoffmann-0stenhof (Chairman), W. E. Cohn (Secretary), A. E. Braunstein, P. Karlson, B. Keil, W. Klyne, C. Li6becq, E. C. Slater, E. C. Webb and W. J. Whelan. Reprints of this document may be obtained from Waldo E. Cohn, Director, NAS-NRC Office of Biochemical Nomenclature, Biology Division, Oak Ridge National Laboratory, Box Y, Oak Ridge, T e n n . 37830, U.S.A.

des igna t ion of t h e B e v i t a m i n s , a n d 'pyr idoxol ' as t he t r iv ia l n a m e for t h e alcohol fo rm (I; R = - C H 2 O H ) p rev ious ly des igna t ed as py r idox ine (Rule V-7) . I n t h e I U P A C - I U B Tentative Rules of 1966 (1) for t h e n o m e n c l a t u r e of v i t a m i n s a n d re la ted c o m p o u n d s (Rule M - 7 . 1 ) , it was sugges t ed t h a t t h e l a t t e r c o m p o u n d shou ld be des igna t ed ' py r idox ine ' or 'pyr idoxol ' .

One regre t t ab le consequence of t hese confl ict ing r e c o m m e n d a t i o n s , g iv ing rise to jus t i f ied cr i t ic ism, is t he con t i nu ing use of t he word ' py r idox ine ' in two dif ferent m e a n i n g s - - a s a gener ic t e r m for sub- s t ances w i th v i t a m i n B 6 ac t iv i ty , and as t h e t r iv ia l n a m e of a defini te chemica l c o m p o u n d (which, inc identa l ly , is one of t he less a b u n d a n t a m o n g t he n a t u r a l l y occurr ing fo rms of v i t a m i n Be).

A n ex t ens ive l i t e ra tu re h a s a c c u m u l a t e d on t he c h e m i s t r y and b iochemis t ry o f t h e B 6 v i t a m i n s a n d eoenzymes , o f the i r me t abo l i t e s a n d o f m a n y re la ted s y n t h e t i c c o m p o u n d s t h a t o f ten exh ib i t biological ac t iv i ty as s u b s t i t u t e s for or as a n t a g o n - is ts of t h e cor respond ing n a t u r a l p roduc t s . A n u m b e r of t r iv ia l a n d semi t r iv ia l n a m e s , s o m e t i m e s incorrec t or a m b i g u o u s , h a v e been coined for v i t a m i n B e de r iva t ives a n d ana logues , a n d severa l fo rms of a b b r e v i a t e d des igna t ions for t hese com- p o u n d s h a v e been in t roduced . Fo r example , t h e abb rev i a t i ons p y r i d o x a l - P , P -py r idoxa l , P L P ( the s y m b o l u sed m o s t f r equen t ly ) , P A L P , Pa lP , P A L P O are in use for py r idoxa l 5 ' -phospha te , a n d s imi lar a b b r e v i a t e d fo rms h a v e been u sed for o the r m e m b e r s of t h e g roup a n d the i r der iva t ives .

T he I U P A C - I U B Commis s ion on Biochemica l N o m e n c l a t u r e (CBN), a t i t s m e e t i n g in J u n e 1968, decided to pub l i sh a special d o c u m e n t , e x t e n d i n g Sect ion M-7 of t he 1966 Ru les (1), to p u t in order t he n o m e n c l a t u r e of t he v i t a m i n B 6 field a n d to un i fy r e l evan t abb rev ia t ions for use in s i t ua t i ons where th i s is essent ia l . The p re sen t Tentative Rules are ba sed on a d ra f t p repa red b y A. E. B r a u n s t e i n a n d E. E. Snell a f te r consu l t a t i on w i th o the r ac t ive workers in t h e field.

R U L E S

[replacing Sect ion M-7 of ref. (1)]

T h e t e r m v i t a m i n B e shou ld be u sed as t he gener ic descr ip tor for all 2 - m e t h y l p y r i d i n e der iva- t ives exh ib i t i ng qua l i t a t i ve ly t he biological a c t i v i t y

Reproduced with kind permission o f the Biochemical Journal, 119 (1970} 1 -4

Biochim. Biophys. Acta, 222 (1970) 1 - 4

2

R R

o cH2o Po 2 - , c " "N"

(I) (II)

COOH C 0 - - 0

H3C" "-N/ H]C - " , N f

(III) (IV)

of pyridoxine. This term should be used in derived terms such as vi tamin B 6 deficiency, v i tamin B 6 activity, v i tamin B~ antagonists (5, 6).

7.1. Compound I (R =-CH2OH), 3-hydroxy- 4,5-bis(hydroxymethyl)-2-methylpyridine, should be designated pyridox/ne or pyridoxol. The alkyl residue formed by removal of the 4 ' -OH group is named pyridoxyl (e.g. in compounds such as N~-pyridoxyl-L-lysin_e and the like).

Comment: 'Pyridoxine' should not be used as a generic name synonymous with 'v i tamin B~' (5, 6).

7.2. Compound I ( R f ~ 3 H O ) should be designated pyridoxal. The bivalent radical formed by removal of the oxygen atom from the CHO group is named l~yridoxylidene.

7.3. Compound I (R ~-CH2NH2) should be designated pyridoxamine.

7.4. The commonly occurring oxidized meta- bolites of pyridoxal, namely 3-hydroxy-5-hydroxy- methyl-2-methylpyridine-4-carboxylic acid (III) and the corresponding lactone (IV), should be designated 4-pyridox/e ae/,d and 4-pyridoxolaetone respectively. (Three less commonly occurring metabolites of pyridoxine, formed by oxidation a t position 5', have also been detected, namely the aldehyde, the carboxylic acid and its lactone; they have been designated by the trivial names 'iso- pyridoxal ' , '5-pyridoxic acid' and '5-pyridoxo- lactone' respectively.)

Vitamin B 6 Phosphates

7.5. The 5'-phosphoric esters of pyridoxine, pyridoxal and pyridoxamine (II ; R = -CH2OH, -CHO, -CH2NH2) should be designated pyridoxine 5'-phosphate (or pyridoxine-5'-P), pyridoxal 5"- phosphat~ (or pyridoxal-5'-_P) and pyridoxamine 5"-phosphate (or pyridoxamine-5 '-P) respectively. The positional numeral, 5'-, may be omit ted where no ambigui ty arises (in biochemical papers etc.);

NOMENCLATURE FOR VITAMIN B 6

ClIO CHO CH 3

H O ~ C H 2 O H H O ~ H O - - P O 3 H 2

H3C / "-N / ~CH 3 H3C / " - N f

(v) (vi)

e.g. pyridoxal 5 '-phosphate may be abbreviated pyridoxal-P.

For convenience (for example in names of derived compounds), i t is admissible to use the symbol P (for 'phosphoric ester') as a prefix, for example: N~-(5'-P-pyridoxyl)-L-lysine; P-pyrid- oxylideneimines.

Derivatives and Analogues

7.6. From the trivial names already indicated, semitrivial names for various derivatives and analogues of the B 6 vi tamins and their phosphoric esters (coenzyme analogues) can be constructed according to the conventional rules of organic nomenclature (see also 7.9). Examples:

5'-deoxypyridoxal, 2-demethylpyridoxal, or 2-norpyridoxal, 2-propyl-2-norpyridoxal, 6-methylpyridoxal (Compound V), 4'-deoxypyridoxine 5'-phosphate, 5 ' -methylpyridoxal-5 ' -P (Compound VI), pyridoxal N-oxide 5'-phosphate.

Abbreviated Designations

7.7. As noted in the Introduct ion, many abbreviat ions have been used in the past to repre- sent the three principal forms of v i tamin B 6, their phosphoric esters and analogues in the text of papers. Those listed in column 2 of the Table have achieved prominence as the favoured forms. Their use in text in place of the approved trivial names (column 1), which are sufficiently short, is not recommended. I t is admissible to use these abbre- viations, with ad hoe definition in each paper (and with the consent of the editors concerned), when necessary in cases of space restriction, e.g. in tables, in figures and in extensive lists of derivatives and their reactions.

Use of Symbols in the Designation of Derivatives and Analogues

7.8. Pyridoxyl (7.1) and pyridoxylidene (7.2) groups and similar residues of v i tamin Bs phos- phates and analogues (7.5, 7.6) frequently occur in natural substances (B6-dependent enzymes), and in modified or synthetic products (e.g. enzymes reconsti tuted with coenzyme analogues or reduced

Biochim. Biophys. Acta, 222 (1970) 1 - 4

I U P A C - I U B COMMISSION ON BIOCHEMICAL NOMENCLATURE

Table . Abbreviated designations

Trivial name (abridged)* Abbreviation~

Pyridoxal PL Pyridoxamine PM Pyridoxine PN Pyridoxal- P PLP Pyridoxamine- P PMP Pyridoxine- P PNP

* Recommended for use in text. t Previous major abbreviations; not recommended for

use in text. Admissible (with ad hoc definition) in special eases, e.g. where required by space limitations (see 7.7); they may also be combined with approved symbols (7) for commonly occurring substituents, e.g. 6MePL (Compound V). Compounds involving the pyridoxyl or pyridoxylidene radicals should generally be symbolized as indicated in para. 7.8 [see ref. (7)]. For isotopic replacement see para. 7.9.

3 idcne-L-aminoacy l res idues a n d t h e cor responding phosphor i c es ters ;

P-(3deoxy)Pxd~=Lys- for t h e N6-(3-dcoxy-5"-P - pyr idoxyl idene)-L- lysyl res idue ;

( 3Me-2nor )Pxy-P

I • . . -Leu-Lys-Gly- . . . for an N6-(3-O-methyl -2 -

nor -5 ' -P ) -pyr idoxy l -L- lysy l res idue in a pep t ide sequence ;

(6Me)Pxd

II . . . - L e u - L y s - G l y - . . . for an N6-(6-methy l -

pyr idoxyl idene) - L - lysyl res idue in a pep t ide s equence ;

P y r i d o x a l - P I

• . . - G l y - S e r - V a l - . . . for a hypo the t i c a l pyr id- oxal-5 '-P-3-O.L-seryl (phosphodies ter) res idue in a pep t ide sequence .

w i th bo rohydr ide or both) , in comb i na t i on wi th a m i n o a c y l or pep t idy l res idues.

To r ep re sen t such der iva t ives in condensed fo rms s imi lar to those r e c o m m e n d e d for s u b s t i t u t e d poly- pep t ides , i t is sugges t ed to use t h e following symbols :

P x y - (hav ing a single bond) for t he py r idoxy l g roup

P x d = (hav ing a double bond) for t he pyr idoxy l - idene group.

T h e cor responding 5 ' - phospho ry l a t ed res idues m a y be de s igna t ed by add i ng t h e s y m b o l P as a h y p h e n a t e d prefix or suffix, a n d c o m m o n a lkyl or acy l s u b s t i t u e n t s b y pref ixes in pa ren theses , com- posed f rom the r e c o m m e n d e d s y m b o l s a n d the i r locan t s (7-9). Examples :

P x y

P x y - L y s - or P x y Lys- or -Lys- or -Lys (Pxy) - for t he N 6-pyridoxyl-L-lysyl res idue ;*

P - P x y

[ I I P-Pxy~-Lys- or P - P x y Lys - or Lys - or -L ys (P -

Pxy ) - for t he cor respond ing N6-(P-pyr idoxyl ) -L- lysyl res idue ;*

P x d ~ L y s - etc. , P-Pxd=~Lys - etc. for t h e N 6- p y r i d o x y l i d e n e - L l y s y l res idue a n d i ts phosphor ic es te r ;

Pxya-Lys - or P x y - V a l - etc. for N2-pyr idoxy l - x~-lysyl a n d o the r N2-py r idoxy l -L-aminoacy l resi- dues ; t

P - P x y - L y s - , P - P x y - V a l - etc. for t he corre- spond ing N2- (P-pyr idoxy l ) -L-aminoacy l r e s i d u e s ; t

Pxd=Val- , P - P x d = V a l - etc. for N2-pyr idoxy l -

* The latter two symbols are more suitable for use in sequences (see last three examples).

t In N-terminal position.

Isotopic Replacement

7.9 . I so topic r ep l acemen t in B 6 v i t amins , co- e n z y m e s a n d der iva t ives can be des igna t ed b y t he conven t iona l no ta t ions . Examples:

[ 3 A S 0 ] p y r i d o x a L P for py r idoxa l 5 ' - phospha t e label led w i th tsO a t 0 - 3 ;

[6 ' -3H,5 -32P]6-methy lpyr idoxamine-P for 6- m e t h y l p y r i d o x a m i n e 5 ' - phospha t e w i th t r i t i u m a t C-6 ' a n d a2p in t he p h o s p h a t e g roup ;

[2' .14C]Pxd II

• . . -Leu-Lys-Ser - . . . for a pep t ide sequence wi th a n N6-pyr idoxyl idene-L- lysyl res idue labelled w i t h 14C a t C-2'.

R E F E R E N C E S

1. Biochem. J. (1967) 102, 15, and elsewhere. 2. Snell, E. E. (1958). Vitams Herin. 16, 77. 3. Braunstein, A. E. (1960). In The Enzymes, 2nd ed.,

col. 2, p. 113• Ed. by Boyer, P. D., Lardy, It. & Myrb~ek, K. New York: Academic Press Inc.

4. J. Am. chem. Soc. (1960) 82, 5581. 5. International Union of Nutritional Sciences (1969).

Tentative Rules for Generic Descriptors and Trivial Names for Vitamins and Related Compounds. Nutr. Abatr. Rev. (in the Pr~s).

6. American Institute of Nutrition (1969). J. Nutr. 99, 244.

7. Amino Acid Derivatives and Peptides (IUPAC-IUB Tentative Rules) (1967}. Biochem. J. 102, 23, and elsewhere (revision in preparation).

8. Abbreviations and Symbols for Chemical Names of Special Interest in Biological Chemistry, 1965 Revision (IUPAC-IUB Tentative Rules) (1966). Biochem. J. 101, l , and elsewhere.

9. Abbreviations and Symbols for Nucleic Acids, Poly- nucleotides and their Constituents (IUPAC-IUB Recommendations) (1970). (in the Press).

Biochim. Biophy~ Acta , 222 (1970) 1 - 4

NOMENCLATURE FOR VITAMIN B 6

All Tentat ive Rules of the I U P A C - I U B Commission on Biochemical Nomen- clature (CBN) as well as a Document for Discussion are available from Waldo E. Cohn, Director, NAS-NRC Office of Biochemical Nomenclature, Oak Ridge National Laboratory, P.O. Box Y, Oak Ridge, Tenn. 37830, U.S.A. :

Abbreviat ions and Symbols for Chemical Names of Interest in Biological Chemistry. Revised Tentat ive Rules [see Bioehem. J. (1966) 101, 1].

Nomenclature of Vitamins, Coenzymes and Related Compounds: Trivial Names of Miscellaneous Compounds of Importance in Biochemistry, Nomenclature of Quinones with Isoprenoid Side Chains, Nomenclature and Symbols for Folic Acid and Related Compounds, Nomenclature of Corrinoids. Tentat ive Rules [see Bioehem. J. (1967) 102, 15].

Abbrevia ted Designation of Amino Acid Derivatives and Peptides. Tentat ive Rules [see Biochem. J. (1967) 102, 23].

Rules of Naming Synthetic Modifications of Natural Peptidcs. Tentat ive Rules [see Bioehem. J. (1967) 104, 17].

The Nomenclature ofLipids. A Document for Discussion [see Biochem. J. (1967) 105, 897].

Abbrevia ted Nomenclature of Synthetic Polypeptidcs (Polymerizcd Amino Acids) [see Bioehem. J. (1968) 11)6, 577].

The Nomenclature of Cyclitols. Tentat ive Rules [see Biochem. J. (1969) 112, 17]. A One-Letter Notat ion for Amino Acid Sequences. Tentat ive Rules [see Biochem.

J . (1969) 113, 1]. Revised Tentat ive Rules for Nomenclature of Steroids [see Biochem. J. (1969)

113, 5].

A document, OBN-5, describing the (American) NAS-NRC Office of Biochemical Nomenclature, and listing other rules affecting biochemical nomenclature, is available from its Director, Dr Waldo E. Cohn [see also J. chem. Docum. (1967) 7, 72].

Biochim. Biophys. Acta, 222 (1970) 1-4