P. F. Blackmore, J. F. Williams, and M. G. Clark
School of Biochemistry University o f New South Wales Kensington, N.S.W. 2033, Australia
I
I
Textbook Errors, 772
Biological Asymmetry of Glycerol
Frequently in textbwks of biochemistry1 the biologically derived terminal monophosphate ester of glycerol is referred to in one or more of the following ways L-a-glycerophosphate, a-glycerophosphate, glycerol phosphate, glycerol 1-phosphate or L-glycerol 1-phosphate, all of which are incorrect. Only occasionally has the recently adopted ( I ) and correct nomenclature been used, namely Sn-glycem-3-phosphoric acid (I) (2). Less conventionally but more frequently L-glycerol 3-phosphate (3) and D-glycerol 1-phosphate are used. The latter two names using D/L nomenclature although formally correct and still acceptable are becomine less often used in the literature. and the stereospcifie numbering system according to the IUPAC-IUB Commission of Biochemical nomenclature is now preferred ( I ) . This system is based on the priorities of the R/S system of Chan, Ingold, and Prelog (4). CH.DH
HO-F-H
I
CH.Q-PO:I
This ester, namely Sn-glycero-3-phosphoric acid is obtained by enzymatic reduction of dihydroxyacetone phosphate by L-glycerol 3-phosphate: NAD oxidoreductase (E.C. 1.1.1.8), acid or base hydrolysis of phosphatidic acid or enzymatic phosphorylation of glycerol by ATP:glycerol phosphotransferase ( E X . 2.7.1.30). This ability of enzymes to distinguish in many cases between chemicallv identical erouns is exdained hv the three point attachment theoryUof ogston (5). ~iolo&cally svnthesized elvcerol from either carboxvl-labelled acetate (6) or [3,4-'4ej glucose (7) gives rise to 4~ labelled glycogen in the liver of the rat, the glucose units of which contain 14C principally in C-3, and C-4, thus studies in uiuo have shown that glycerol although apparently a symmetrical molecule is metabolized asymmetrically in confirmation of the hypothesis of Ogston (5). Chemically prepared glycerol labelled with 14C in the terminal carbon (8) may be considered as DL-[I-l'C] glycerol or Sn-[1,3-"C] glycerol (7, 9, 10) since during metabolism in uiuo of this compound, it behaves as a mixture of Sn-[3-14C] and Sn-[lI4C] glycerol because [1,3,4,6-14C] glucose is formed (11); this being consistent with reaction (11.2 *THDH
ATP
'CH,OH
a o ~
HO-7-H:
*H -"
111
*CH:OH
ATP
'CH~OH
H~+H
194.
(31 MeGilvery, R. W.. "Bhchemistry A Functional Appmaeb," W . B. Saundcm Co.. Philadelphia, 1970.p. 251. (11 Cahn. R. S., Ingold, C. K.. and Relq. V.. Angou. ChDm Intern. Ed. Engl., 5. 385
(19661.
(51 Ogston, A. O..Nafure. 162.963(19481. (61 Seharnbye. P., andWmd. H. G.. J. B i d Cham.. M6.875(1.W) 171 Sviek. R. W.. andNako.A..J. B i d Chem... 2M. . 883119541. L. I., Bnd ~ ~ M. L., J A~ ~ ~ chpm. , . ~ Soc., 74. 241s ~ (1952). ~ i is (9) Blackmore. P. F.. Clark. M. 0.. and Williams, J. F.. J. Lobslkd Compounds.. 8. (101 Genauose,J., Schmidt, K., andKatz, J.,AwI. Biach~m..34.161 (19701 '111 Doemchuk, A. P.J. B i d Chsm., 196.423(19521.
Sn-11. 3-"Cl plycero-3-P
am
(11 "TheNomenclatu?eofLipids."Biorhem., 6.3287 (1967). (21 Lchninger, Albert. L., 'lBiacbemiatry," Worth Publishers. Inc., New Yark. 1970. p.
71 ,1971,
which is catalyzed by ATP: glycerol phosphotransferase. On the other hand, biologically prepared [I-'4C] glycerol, which results in the synthesis of [3,4-14C] glucose (6, 7), is consistent with reaction (2) for the phosphorylation of glycerol. Thus biologically synthesized [I-14C] glycerol can be considered as Sn-[I-*4C] glycerol or L-[I-14C] glycerol. HO+
Literature Cited
. .,...-,.
'CH~O-PO,?-
*~H~OH Sn-11. 3-"CI elyceral
In conclusion, many textbwks of biochemistry incorrectlv name the naturallv occurrine" nhosnhate ester of . . glycerol, which arises from reduction of dihydroxyacetone phosphate by the enzyme L-glycerol 3-phosphate:NAD oxidoreductase. For example the L-rr-glycerol phosphate naming of the ester does not distinguish between L-glycerol 1-P or L-glycerol 3-P because the use of a nomenclature does not allow a choice to be made between the two alternatives. While the use of L-glycerol I-phosphate is entirely erronous where the authors have used conventional numbering nomenclature of organic compounds to describe the position of the phosphate group, it is interesting to note that this is the isomer obtained by chemical reduction of D-glyceraldehyde 3-phosphate. When students are confronted with the different types of nomenclature, for example, L-glycerol 1-phosphate and L-glycerol 3phosphate (which is the correct naming), in different texts, they may be led to conclude that both isomers exist in uiuo, which of course is erroneous. In order to be both correct and a t the same time properly educate the student, authors of biochemistry textbooks should be consistent and accurate with their nomenclature in naming glycerol phosphate and all symmetrical intermediw compounds and products. I t is of course most interestmi and "seful to feature as examples enzymes which act on apparently symmetrical molecules in an asymmetric fashion. I t is also imperative that the graduate student or researcher who may be studying the metabolic fate in uiuo of the individual carbon atoms of '4C specifically labelled glycerol, appreciates that chemically prepared (8) '4C-terminally labelled glycerol is metabolized in a different manner, in respect to the intennediary distributions of 14C, to that of biologically prepared Sn-[I-'4C] glycerol which is the only specifically labelled compound.
i ~ i
Suggestions of material suitahle for this column and columns suitable far publication directly should he sent with as many details as possible, and particularly with reference to modem textbmks, to W. H. Eherhardt, School of Chemistry, Georgia Institute of Technology, Atlanta, Georgia 30332. 1 Since the purpose of this column is to prevent the spread and continuation of errors and not the evaluation of individual texts, the sources of errors discussed will not he cited. In order to be presented, an e m must occur in at least two independent recent standard hooks. >Theasterisk indicates the position of theW2. Volume 50, Number 8, August 1973
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