The Embden-Meyerhof Pathway

Glucose is the energy source of the red ceU. In the normal situation (without increased oxidative stress )) 90% of glucose is catabohzed anaerobically to pyruvate or lactate by 

Although the pathway is reasonably straightforward, it is subjected to a complex mechanism of inhibiting and stimulating factors. Some of the enzymes involved are allosterically stimulated by products of the pathway (such as pyruvate Idnase [PK] by fructose diphosphate), while others may serve as strong inhibitors (such as glucose 6-phosphate for hexo-kinase [HK]). 

Hexokinase (HK EC 2.7.1.1) catalyzes the phosphorylation of glucose to glucose-6-phosphate (G6P) using ATP as a phosphoryl donor. The activity of HK is significantly higher in reticulocytes compared with mature red cells, where it is very low. The HK reaction is one of two rate-limiting steps in this pathway, the other being the phosphofructokinase reaction. 

In mammalian tissues, four isozymes of HK with different enzymatic properties exist, HK-I to III with an Mr of 

000 kDa. HK-I to III are considered to have evolved from an ancestral 50 kDa HK by gene duplication and fusion. Consequently, both the C- and N-terminal halves of HK-I to HK-III show extensive internal sequence similarity, but only in the case of HK-II was catalytic function maintained in both the C- and N-terminal halves, HK-I and HK-III have further evolved into enzymes with respectively catalytic (C-terminal) and regulatory (N-terminal) halves. 

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Yeast (qv) metabolize maltose and glucose sugars via the Embden-Meyerhof pathway to pymvate, and via acetaldehyde to ethanol. AH distiUers yeast strains can be expected to produce 6% (v/v) ethanol from a mash containing 11% (w/v) starch. Ethanol concentration up to 18% can be tolerated by some yeasts. Secondary products (congeners) arise during fermentation and are retained in the distiUation of whiskey. These include aldehydes, esters, and higher alcohols (fusel oHs). NaturaHy occurring lactic acid bacteria may simultaneously ferment within the mash and contribute to the whiskey flavor profile. 

All overview of the glycolytic pathway is presented in Figure 19.1. Most of the details of this pathway (the first metabolic pathway to be elucidated) were worked out in the first half of the 20th century by the German biochemists Otto Warburg, G. Embden, and O. Meyerhof. In fact, the sequence of reactions in Figure 19.1 is often referred to as the Embden-Meyerhof pathway. 

Defects in the Embden-Meyerhof Pathway 3.2.1. Hexokinase Deficiency... 

For many years, it was considered that the Embden-Meyerhof pathway was the major route of carbohydrate metabolism in a wide variety of organisms. However, evidence has been slowly accumulated to suggest that alternative routes exist. 

You will probably be familiar with glycolysis (the Embden-Meyerhof pathway, Figure 1.20) from previous studies at school perhaps, so let s use this important pathway to illustrate some points in the recommended strategy. 

With the advent of PM3, biochemical reactions, for example, those involved in the Embden—Meyerhof pathway, can be studied. Until now, systems such as glucose-6—phosphate were either poorly represented, or were prohibitively slow to calculate. 

An alternative pathway to the Embden-Meyerhof pathway of glycolysis for conversion of carbohydrates to pyruvate is the pentose-phosphate pathway (Fig. 5.13). Its main role is not ATP production but to provide NADPH for fat synthesis, and pentoses (in particular, D-ribose-5-phosphate) for nucleic acid synthesis. The pathway can also convert pentoses to hexoses, which can then be further metabolised by glycolysis. With regard to cestodes, a... 

Schroder, C., Selig, M., and Schonheit, P. 1994. Glucose fermentation to acetate, C02 and H2 in the anaerobic hyperthermophilic eubacterium Thermotoga maritima involvement of the Embden-Meyerhof pathway. Arch. Microbiol., 767,460-470. 

The action of ammonia on cytidine ribitol pyrophosphate (III) gave a cyclic phosphate IX which was oxidized by periodate and bromine to yield X, the cyclic 2,3-0-phosphate of glyceronic acid. This substance was purified by paper chromatography, and hydrolyzed with acid to the 2-phos-phate (XI) and 3-phosphate (XII) of D-glyceronic acid. These substances were utilized by a multi-enzyme system from rabbit muscle which degrades carbohydrates by way of the Embden-Meyerhof pathway. The ribitol phosphate (VII) is therefore L-ribitol 1-phosphate (o-ribitol 5-phosphate). ... 

Two metabolic patterns are discernible from the results. Carbon atoms 2, 1, and 7 of shikimate (VI) are derived almost equally from G-1,6, G-2,5, and G-3,4, respectively. In the Embden-Meyerhof pathway of hexose metabolism (see Fig. 2), D-fructose 1,6-diphosphate is cleaved to 1,3-dihydroxy-2-propanone phosphate (G-1,2,3) and D-glycerose 3-phosphate (G-4,5,6), and the two trioses are interconverted by triose phosphate isomerase. The observed randomization of label between Cl and C6, C2 and C5, and C3 and C4 of hexose therefore implies that C2, Cl, and C7 of shikimate are derived from a 3-carbon intermediate of glycolysis. The small but significant preponderance of G-6 over G-1, of G-5 over G-2, and, presumably, of G-4 over G-3, can be explained by recent observations that, in the aldolase cleavage of D-fructose 1,6-diphosphate, the 1,3-dihy-... 

Fig. 2.—a Schematic Representation of the Embden-Meyerhof Pathway to Show the Distribution of Label from n-Glucose in the 3-Carbon Intermediates of the Pathway. [P denotes —PO(OH)j.]... 

Since the completion of this manuscript in 1992, Schafer and Schonheit [ 110] have demonstrated that gluconeogenesis in P. furiosus proceeds via the reactions of the Embden-Meyerhof pathway (see section 2.4). 

As previously mentioned and in the earlier discussion of fermentation methanol, bacteria of the genus Zymomonas such as Z. mobilis are known to convert hexoses to ethanol at high yields and short residence times. These bacteria are facultative anaerobes that have fermentative capacity and convert only glucose, fructose, and sucrose to equimolar quantities of ethanol and CO2 the pentoses are not converted. The Entner-Doudoroff pathway is utilized instead of the Embden-Meyerhof pathway, and a net yield of 1 mol of ATP is generated, not 2 mol as in bakers yeast. But pyruvate is the same key intermediate. In Z. mobilis, it is decarboxylated by pyruvate decarboxylase to yield acetaldehyde which is then reduced to ethanol by alcohol dehydrogenase. 

The Embden-Meyerhof pathway via pyruvic acid is the normal route to fermentation products from biomass carbohydrates (Chapter 11). Enteric bacteria appear to have the unique capability of converting pyruvic acid directly to formic acid (Section I1,D) ... 

Figure 21 -8 Major glycolytic pathways of the erythrocyte. Substrates are in uppercase type, and enzymes are in parentheses. EMP, The Embden-Meyerhof pathway HMP hexose monophosphate pathway or pentose shunt RLC, the Rapoport-Luebering cycle ADP, adenosine diphosphate ATP, adenosine triphosphate NAD, nicotinamide-adenine dinudeotide NADH, reduced nicotinamide-adenine dinucleotide NADP, nicotinamide-adenine dinucleotide phosphate NADPH, reduced nicotinamide-adenine dinucleotide phosphate.The step from ribulose-5-phosphate, which is shown as being catalyzed by transketolase and transaldolase, is an abbreviation of this portion of the HMR...

Nicotinamide adenine dinudeotide (NADH)-cytochrome b5 reductase (EC 1.6.2.2 cytbSr) uses NADH generated in the reaction in the Embden-Meyerhof pathway by glycer-aldehyde 3-phosphate dehydrogenase, to reduce the 12kDa protein cytochrome b5. Cytochrome b5 in turn reduces methemoglobm to hemoglobin. 

Figure 4.1 Homolactic fermentation. The fermentation of one mole of glucose yields two moles of lactic acid via the Embden-Meyerhof pathway.

Be familiar with the Embden-Meyerhof pathway of RBC metabolism. 

The Embden-Meyerhof pathway ends with the production of pyruvic acid when, however, oxygen is not in short supply, the pyruvic acjd is itself further oxidized to carbon dioxide ... 

The Embden-Meyerhof pathway.and the citric acid cycle, whilst amongst the most universal of glucose oxidation systems found in nature, are by no means the only ones. Many variants on the citric acid cycle are known to exist in different organs and species, and several alternative cycles or shunts have been suggested. That the cycle itself occurs in almost all tissues has been confirmed abundantly, in particular by the use of isotopic tracers, but it is often difficult to obtain a quantitative estimate of the extent to which the glucose oxidized in the living cell uses the cycle or is diverted to other routes. 

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