Embden-Meyerhof scheme

D-Erytbrose 4-Phosphate. [R-(R, R )]-2,3-Di-kydroxy-4-(pkosphoitaoxytbuuinal 4-D-eryrftrojep/tosp/toric acid. CjHjOjP mol wt 200.08. C 24.01%, H 4,53%, O 55.98%, P 15.48%. Occurs in minute amounts in muscle flesh of all animals. Important natnral intermediate in the Embden -Meyerhof scheme of alcoholic fermentation and glycolysis. Prepn hy chemical synthesis Ballou cl al, J. Am. Oiem. Sac. 77, 2658, 5967 (1955). Outline Chem. Eng. News 34, 2506 (1956). 

The three major processes in carbohydrate metabolism, namely the Calvin cycle of photosynthesis (Figure 11.19), the Embden-Meyerhof scheme of glycolysis (Figure 11.20) and the Krebs cycle of respiration (Figure 11.21) all require ATP and/or other phosphate esters such as NAD+, NADP or Acetyl-CoA to act as energy carriers. Both ATP and NADPH are involved in the fixation of nitrogen and numerous other biochemical cycles (Section 11.5). 

These reactions have been designated the Embden-Meyerhof scheme, in recognition of the pioneer discoveries that led to the acceptance of this pathway, but workers in many other laboratories have contributed heavily to the study of the glycolytic enzymes. The reactions indicated as unidirectional are in fact reversible, but under ordinary circumstances the reverse reactions do not occur to significant extents. In order to reverse the glycolytic system, additional reactions by-pass the irreversi-O. H. Lowry, N. R. Roberts, and C. Lewis, J. Biol. Chem. 220, 879 (1956). 

Glyoxalase. Before the Embden-Meyerhof scheme was recognized as the major pathway for glucose metabolism, an enzyme was found that could produce lactic acid rapidly. It was reasonable, therefore, that this enzyme, glyoxalase, and its substrate, methyl glyoxal, were used in many speculations about the nature of glycolysis. Today they are not... 

Although it is true that the Embden-Meyerhof scheme traces the most general form of the start of carbohydrate catabolism, there exists an alternative route, oxidative in nature, which with a fragment of the glycolysis... 

The intermediary metabolism of carbohydrate is discussed in Chapter 4, to which the reader is referred for details of the enzymatic conversion of hexoses, the formation of glycogen, and the Embden-Meyerhof scheme of glycolysis. Terminal oxidation of carbohydrate is also discussed the oxidation and reactions of pyruvic acid, the monophosphate shunt, and the tricarboxylic acid cycle are illustrated diagrammatically. 

Embden-Meyerhof scheme, and page 250, plus or minus a couple, Lipmann s previously mentioned analysis of pyruvate oxidation in a lactic acid bacterium, and only a year later Wiggle P, P on page 99, Advances in Enzymology,... 

The possibility that these pathways of glucose degradation are entirely nonphosphorylative is unlikely, as will be seen below. Nevertheless, to a certain extent, the nonphosphorylated compounds parallel the pathway of oxidative degradation of glucose-6-phosphate. As these facts imply, we shall not be concerned with merely one but with several alternative pathways to the Embden-Meyerhof scheme. 

Fig. 11. The fate of the carbon atoms of glucose in (A) the oxidative pathway and (B) the formation of pyruvate in the Embden-Meyerhof scheme.

By known pathways of metabolism, the j3-carbon of pyruvate forms CO2 only under conditions in which the entire moiety is oxidized to C02 and water. Therefore, by means of the Embden-Meyerhof scheme, the proportion of Ci in total CO2 should never exceed the proportion of Ci in glucose carbon or 1 6. However, the decarboxylation of 6-phosphoglu-conate must lead to a selective appearance of Ci in the total CO2. Under conditions in which this pathway is very active and some carbon is conserved, as in growth or other synthesis, this use of the pathway will be revealed by a higher proportion of Ci in total CO2 than its proportion in the initial carbohydrate carbon. 

The study of these metabolic steps is quite active at the present time. As noted above, Dickens found that ribose-5-phosphate was fermented anaerobically to ethanol, a 2-carbon compound, inorganic phosphate, and CO2. Racker observed that extracts of E. colt converted ribose-5-phosphate to a triose phosphate, which could be analyzed in the presence of triose phosphate isomerase as dihydroxyacetone phosphate.Therefore, the products of the oxidative pathway eventually join the Embden-Meyerhof scheme at the triose phosphate stage, the major difference being the formation of 2 moles of triose phosphate in the latter pathway and only 1 mole via the phosphogluconate pathway. 

Several investigators had observed the formation of hexose phosphates during nucleoside and pentose metabolism by cell extracts. It was considered until recently that these hexose phosphates arose from a reversal of the Embden-Meyerhof scheme operative on triose phosphate derived from pentose. It has now been found by Dische that more hexose may be generated from adenosine in hemolysates than would be expected from the proportion of 3-carbon fragments in the pentose molecule, i.e., 0.75 mole hexose per mole pentose instead of a maximal 0.6. Furthermore, much of the carbon of the pentose was in hexose monophosphate produced under conditions in which hexose-6-phosphate and hexose-1,6-diphosphate were not interconvertible. 

Some cells lack certain enzymatic steps and therefore lack certain pathways. Studies of the homo- and heterofermentative organisms are instructive in this regard. In the homofermentative lactic acid bacteria, the utilization of C Mabeled glucose to form lactate and the distribution of in the lactate suggest that the basic degradative procedure is that of the Embden-Meyerhof scheme. An observed slight randomization of... 

Thus we find an organism, Leuconostoc mesenteroides, which can only ferment glucose by the way of phosphogluconate because of the presence of only the enzymes of the phosphogluconate pathway. Conversely, it has already been noted that muscle is low in the dehydrogenases of this system, and it might be anticipated that this tissue would reveal the use of glucose predominantly by the Embden-Meyerhof scheme. 

Among cells which have both systems, yeast ferments glucose predominantly by the Embden-Meyerhof scheme and Pseudomonas lindneri uses the oxidative pathway. To E. coli having both, as will be discussed below, both mechanisms are quite important in the normal economy of the cell growing on glucose. 

A recent study (Bloom, B., Stetten, M. R., and Stetten, D., J. Biol. Chem. 204, 681 (1953)) of the catabolism of isotopic glucose in mammalian systems has confirmed this utilization of the Embden-Meyerhof scheme in muscle. Even more interesting, however, is the result that at least 75% of glucose utilization in liver proceeds by a non-glycolytic pathway wherein the C, of glucose is preferentially converted to CO2. 

Under conditions of virus infection with the same CO2 production per mole of glucose, 29% of the Ci was contained in the CO2. This is equivalent to a maYinmiTTi of 29% of the glucose metabolized via the oxidative pathway or a minimum of 6%. These differences were real and reproducible and are of the same order as the shifts in the amounts of pentose and desoxypentose synthesized during glucose utilization. It was suggested as a result of these studies that the ribose of RNA was derived mainly via the oxidative pathway, whereas the desoxyribose of DNA arose from triose phosphate generated from the Embden-Meyerhof scheme. 

It has been suggested that the basic mechanism of ribose synthesis in this animal involves a 2-carbon -b 3-carbon condensation of fragments derived from the Embden-Meyerhof scheme. On the other hand, since the conditions of the experiment did not involve a net synthesis of RNA, it is possible that the phosphogluconate path was operative but that a dilution of the 2-carbon fragment occurred by exchange reactions at the ribulose-5-phosphate level. It may be noted that both mechanisms involve the reversibility of the reaction. 

Engel hardt and Barkash have attributed the more efficient use of glucose in the presence of oxygen by various cells to the existence of a pathway other than the Embden-Meyerhof scheme. Lipmann observed the inhibition of glycolysis by oxidizing agents, and Engelhardt and... 

In addition to the Embden-Meyerhof scheme, at least two other pathways for glucose utilization have been unequivocally demonstrated, as presented in Fig. 23. The conversion of glucose to uronic acid and hexosa-... 

Triose can enter one of two pathways Either it is broken down further according to the Embden-Meyerhof scheme (see below), or two molecules of triose condense to form a new molecule of hexose (fructose diphosphate) which may reenter the cycle. It is possible, therefore, to decompose hexose completely to CO2 and coenzyme-bound hydrogen (NADPH2). Unlike NADH2, NADPH2 cannot produce... 

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