48 BIOCHEMICAL EDUCATION July 1976 Vol. 4 No. 3

Formula 3

CI H2--O-- P .J~/oOH CH 3 \ O H = I + H3PO 4

CHOH C = 0 1 I

COOH COOH

Phosphoglyceric A. Pyruvic A.

through a series of phosphorylated compounds, but he had the fertile imagination to recognize all the important intermediaries. And yet it is rather startling, when reading EMBDEN'S paper now, to see that after all this success in developing, with amazing intuition, the right skeleton scheme for glycolysis, he was still reluctant to accept the phosphorylated intermediaries as the true inter- mediaries in glycolysis. Somewhere in his mind a doubt still remained. This, I would guess, was due to the fact that at that time he really could not quite understand why the phosphate came into fermentation and glycolysis because he did not realize how it was functioning there.

Figure 1 brings the puzzle to a final solution, including the question of what inorganic phosphate had to do in fermentation. The latter, as you know, was resolved in WARBURG'S laboratorya~: the finding that phosphoglyceraldehyde + phosphate is oxidized not to phosphoglyceric acid but to phosphoglyceryi phosphate, that is, the anhydride between its carboxyl and phosphoric acid; then phosphoglyceryl phosphate transfers its energy-rich carboxyl anhydride phosphate obligatorily to ADP to yield ATP. The sequence in Figure 1 gives glycolysis as we formulate it now, namely, that the first reaction is an energy-requiring reaction. That explains the long induction period in cell-free fermentation, since it appears that all such compounds that can transfer energy-rich phosphate will shorten or abolish the induction. Thus, the first step is the phosphorylation of the hexose to FDP, which splits to two interconvertible triose phosphates, of which phosphoglyceraldehyde is normally used; then the DPN-linked oxidation of phosphogly- ceraldehyde + inorganic phosphate to phosphoglyceryl ~ P + DPNH refunds the used energy-rich phosphate by converting Redox potential into "-- P-potential. But, energetically, that would still only balance out; however, the additional energy-rich phosphate that is formed in fermentation results from the conversion of phospho- glycerate. The 3'-phosphoglycerate, after conversion to 2'- phosphoglycerate, equilibrates to form the energy-rich phospho- enolpyruvate; this reacts again with ADP, which throws the second energy-rich ~ P into the ATP, leaving pyruvate to be reduced by DPNH to lactate. Thus, we now understand that not only DPN/ DPNH but also ATP/ADP are coenzymes for glycolysis and alcoholic fermentation, acting as links in the metabolic energy transformation.

ph- ph- ph- ph"-'

hexose/2, ph glyceraldehyde + ph g I ycer yl'-' ph glycerate -H20 enolperuvate ,- , - , p h

pyruvate +2H lactate

Figure I

This brings me to the end, and I hope I have been able to give you some of the excitement those who were involved in this type of work went through during that period. I have tried to revive the revelation we got from EMBDEN'S extraordinary intuition which welded together a coherence where others had only 'seen the trees but not the woods'. I have since heard a good deal from Gerhard SCHMIDT about this man for whom he had the greatest admiration. It is very sad that EMBDEN died soon after this discovery. But his name has remained attached to glycolysis, in that we still talk of its mechanism as the EMBDEN-MEYERHOF cycle.

Let me close with a word about the characteristics of these two men: EMBDEN, with whom Gerhard worked and MEYERHOF, who was my guide. I would say that I agree with those people who sort scientists, as they do painters and writers, into romantics and classics, and to me one of the best examples of a romantic scientist is EMBDEN and of a classic scientist, MEYERHOF.

REFERENCES i G. Embden, H. J. Deuticke, and G. Kraft, Klin. Wocbensch. 12, 213 (1932).

z A. Harden and W. J. Young, Proc. Royal SOc. (London) B (1906), p. 77.

3 F. Lipmann, Biochem. Z. 274, 329, 412 (1934).

4 A. Harden, Alcoholic Fermentation, London, Longmans Green, 4th ed., 1932.

s R. Nilsson, Arkiv f6r Kemi, Mineralogi och Geologi, 10A, 1 (1930).

s K. Lohmann, Biochem. Z. 222, 324 (1930).

7 F. Lipmann and K. Lohmann, Biochem. Z. 222,389 (1930).

s O. Warburg and W. Christian, Biochem. Z. 303, 30 (1939).

9 E. Negelein and H. Br6mel, Biochem. Z. 303, 132 (1939).

Index to Biochemical Reviews, 1975 Compiled by Ruth E. Arnstein, Mary Harvey and H. R. V. Arnstein. Published by North-Hol land of Amste rdam on behalf of the Federat ion of European Biochemical Societies (F.E.B.S.) . 1976. Pp 60.

Indexes for 1971-72, 1973, 1974 or 1975: DM 1S.00 (U.S.$ 6.00) each; Any two: DM 25.00 (U.S.S. 10.00); any three DM 35.00 (U.S.$ 14.00); all four DM 45.00 (U.S.$18.00) . May be obta ined from Professor S. P. Dat ta , Biochemistry, University College, London WC1E 6BT, England. Remittance, payable to " F E B S " m u s t be sen[

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The Index for 1975 is the fourth annual compilation and is a reprint of a supplement to the June 1976 issue of FEBS Letters. Reviews of previous issues were reviewed in Biochemical Education, 1974, 2, S0 and 1976, 4, 2. References are given to about 2000 reviews on biochemical topics which were published in 1975 and classified under around 170 headings, such as Caleitonin, calcium, cancer, carbohydrates, catecholamines . . . etc. As the Index has appeared in print within six months of the end of the year it covers, biochemists will find this a valuable guide to recent literature.

B. A. Kilby