Biochemical Engineering Fundamentals, Part 1 - Bailey J., Ollis D. 1989

Stoichiometry and Energetics of Metabolic Transformations
Carbon Catabolism
Embden - Meyerhof - Parnas Pathway

The processes of nutrient breakdown aimed at energy extraction are called Catabolism. CARBOHYDRATES serve as the source of carbon-containing nutrients in the overwhelming majority of cases, although some microorganisms can also utilize Amino Acids, Hydrocarbons, and Other Compounds. The Diversity of the microbial world is illustrated by the fact that virtually any carbohydrate or related compound can be assimilated by one microorganism or another. Most microorganisms capable of utilizing carbohydrates can also process glucose, the most common monosaccharide. In the following section, we will examine the main PATHWAYS OF GLUCOSE degradation. There are at least seven different pathways of Glucose Catabolism. The Nature of the microorganism determines which of these mechanisms is implemented and what end products are formed. Here, our primary focus will be on the participation of the energy and electron transfer processes discussed above, the overall Stoichiometry of the metabolic pathway, and the identification of Key Intermediates along this path.

The Embden–Meyerhof–Parnas (EMP) pathway, shown in Fig. 5.1, involves ten enzyme-catalyzed steps starting with glucose as the initial substrate and yielding Pyruvate as the final product of the reaction sequence (Fig. 5.4). In this section, we will examine this most thoroughly studied pathway of Carbon Catabolism, paying special attention to energetics and reduction processes.

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FIG. 5.4. The Embden–Meyerhof–Parnas (EMP) pathway. Note that each six-carbon substrate molecule (glucose) yields two three-carbon intermediates, each of which undergoes the sequential transformations depicted on the right side of the figure.

An Analysis of the reaction sequence of the EMP pathway shown in Fig. 5.4 reveals that each step is a simple isomerization, ring Cleavage, or migration of small groups, such as hydrogen atoms or a phosphate group. Ultimately, two moles of pyruvate are formed from one mole of glucose. The first and third reactions occur in conjunction with ATP Hydrolysis; these reactions do not proceed spontaneously in the required direction. Two other stages are associated with the release of Free energy sufficient for ADP phosphorylation; these two reactions occur twice during The conversion of each molecule of starting glucose, so the net result of the EMP pathway is the phosphorylation of ADP. As shown in Fig. 5.4, the dehydrogenation of glyceraldehyde-3-phosphate is coupled with the reduction of NAD⁺, and this reaction occurs twice per glucose molecule converted. Thus, the overall stoichiometry of the EMP metabolic pathway can be expressed by the following equation:

The conversion of glucose to pyruvic acid provides Cells with reserves of chemical energy and reducing equivalents. Energy storage through the conversion of this or any other substrate is called substrate-level phosphorylation.

The EMP metabolic pathway also performs another important function related to supplying starting Materials for a series of biosynthetic reaction sequences. Not only pyruvate, but also A number of intermediates of this metabolic pathway are used as biosynthetic substrates (precursors) (see Fig. 5.1). For this reason, the EMP metabolic pathway is called amphibolic (like some other metabolic pathways), implying that it provides The Cell with both Energy Sources and starting materials.

In Muscle tissue cells and lactic acid Bacteria, as well as in a number of other cells, the EMP pathway does not terminate at the pyruvate stage, but is extended by one more step:

The entire sequence of reactions starting with glucose and ending with lactic acid is called Glycolysis. It is interesting to compare the free energy change in glycolysis:

with the free energy change of The breakdown of a single glucose molecule:

It follows from equations (5.13) and (5.14) that energy equivalent to 14.6 kcal/mol of glucose (or 7.3 kcal/mol of ATP) is conserved in the form of high-energy phosphates. The apparent efficiency of free energy transfer is 14/47 × 100 = 31%. Adjusting for actual concentrations and the prevailing in vivo pH (see Table 5.3) shows that this estimate is significantly understated, and the true efficiency is about 53%. The reason for such a substantial difference between the apparent and actual efficiencies becomes clear after correcting the $\Delta G^\circ'$ values given in Table 5.3 in accordance with actual concentrations (see Exercise 5.4); the correction results show that $\Delta G'$ is approximately zero for all steps except three (the conversion of glucose to G6P, F6P to FDP, and PEP to Pyr; Structure/97.html">Definitions of Abbreviations are given in Table 5.3). Thus, most elementary reactions in the EMP sequence are near-equilibrium and, consequently, reversible. We will understand The Significance of non-equilibrium steps for the overall process after studying the enzymatic Regulation of the EMP pathway (Sec. 5.7.2).

Table 5.3. Concentrations of intermediates involved in glycolysis in human erythrocytes and the corresponding Standard Free Energy changes. Note that the concentrations of all substances differ significantly from the 1 M value used in defining the standard free energy. The $\Delta G^\circ'$ values correspond to the steps involving the intermediate specified in the given row^a

^aFrom: Lehninger A. L., Biochemistry, 2d ed., table 16.1, Worth Publishers, Inc., New York, 1975.