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4.4Intracellular Metabolism

Intracellular metabolism consists of many different enzymatic reactions. While several important pathways are shared among organisms, some are specific to each organism (group). Intracellular metabolism basically consists of three stages (Fig. 4-3).
(1) Synthesis and decomposition of substances
Complex substances (organic compounds) that function in the body, such as proteins, polysaccharides, and complex lipids (some of which are macromolecules), are composed of units of amino acids, monosaccharides, and fatty acids, respectively. These substances revert to these basic units on degradation.
(2) Conversion through intermediate metabolites
In case of carbohydrates and lipids, the units comprising these organic compounds are produced through formation of intermediate metabolites and redox reactions between simple basic metabolites.
(3) Interconversion
Basic metabolites are mutually converted by redox reactions, phosphorylation, dephosphorylation, etc.
In process (1), each metabolic pathway is independent. Furthermore, descriptions of the specific structures of biological materials will be provided in Chapter 6. In (2) and (3), the formation and breaking of carbon–carbon bonds are important. In particular, hexose synthesis through condensation of two trioses (by aldolase), citric acid synthesis through condensation of acetyl-CoA, and oxaloacetate (by citric synthetase) and fatty acid syntheses through condensation of acylated enzyme and malonyl-CoA (by fatty acid synthetase) are each important as methods for formation carbon–carbon bonds in the body. These reactions are all performed using the reactivity of carbonyl groups (Fig. 4-4).

Fig. 4-3 Schematic Diagram of the Basic Metabolic Pathway

Glu, glutamic acid; Asp, aspartic acid; Ala, alanine; FBP, fructose-1,6-bisphosphate; G3P, glyceraldehyde-3-phosphate; OAA, oxaloacetate; 2-OG, 2-oxoglutarate

Fig. 4-4 Examples of Carbon–Carbon Bond forming Reactions

In amino acid synthesis, amino groups are formed by a reaction between carbonyl groups and ammonia. For example, alanine is synthesized from pyruvic acid and aspartic acid from oxaloacetate.

The representative reaction for NADH generation is the removal of carbon dioxide from the carbonyl group at the end of R-CO-COOH by enzymes, such as pyruvate dehydrogenase. In respiration, oxygen is inhaled and carbon dioxide is exhaled, but at the cellular level, carbon dioxide release is performed separately from oxygen absorption.

When the metabolic system is viewed from the perspective of energy, decomposition of complex substances into units in (1) has a negative ΔG and hence simply occurs via hydrolysis. Conversely, the synthesis of complex substances requires the addition of energy, which is achieved by conjugation with reactions like ATP hydrolysis.. In metabolism, in many cases, the conversion of substances must be performed bidirectionally. However, if a reaction has a negative ΔG in one direction, it will have a positive ΔG in the opposite direction, and thus, the reaction cannot proceed spontaneously. Therefore, it is necessary to catalyze different reactions using different enzymes and observe the point at which ΔG of the overall reaction becomes negative by conjugating (occurring simultaneously as one comprehensive reaction) reactions with a reaction with a high negative ΔG value, such as ATP hydrolysis (Fig. 4-3, "Energy-requiring reaction". If ΔG of a reaction is negative, then hydrolysis reveals no results (Fig. 4-3, "Hydrolysis"). However, if there is sufficient energy, then it can be conjugated with ATP or NADH synthesis to extract energy (Fig. 4-3 , "Energy-producing reaction"). In carbohydrate and fatty acid metabolism, reducing power is obtained during their decomposition into basic metabolites and is consumed during their synthesis. Energy is lost during the reaction; hence, the overall energy may not be sufficient when a substance is converted in this manner. Therefore, energy must be obtained through partial decomposition of carbohydrates or fatty acids for the occurrence of cellular activity. For this reason, glycolysis and β-oxidation are generally explained as energy acquisition methods. Therefore, an overall influx of substances (top of Fig. 4-3; substances with high energy content) must occur for the survival of heterotrophs such as humans and Escherichia coli. This does not indicate that these substances are produced from nothing, but they are rather synthesized by photosynthetic organisms, such as autotrophs, using sunlight as an energy source (see Fig. 4-2).

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Fermentation in a Cell-free System

In the 19th century, chemistry was actively studied to explain biological phenomena and examine substances that constitute living organisms, resulting in the establishment of organic chemistry. Thus, we can consider that organic chemistry has developed from research targeting biochemistry. The word “organic” originally was specific to organisms. In 1833, diastase was extracted from malt solution during starch hydrolysis. However, at that time, it was very difficult in organic chemistry (biochemistry) to reproduce complicated biochemical reactions occurring in organisms in test tubes. In 1897, the German biochemist Eduard Buchner who had been studying fermentation with yeast added a great quantity of sucrose, which was used as a preservative for perishable goods (jams etc.), in an attempt to preserve lysed yeast cells. As a result, foam bubbled from the mixture, and this was the first evidence of fermentation. At that time, quartz sand was used for cell lysis. However, he completely ground the cells with sand and used a high-pressure hydraulic press to squeeze them, thus deforming the cells. This was the generation of a cell-free system in which the cells are broken and the biochemical reactions can be studied in a test tube. This led to the discovery of various enzymes related to fermentation, and later, to an understanding of the basic metabolic pathway called the glycolytic pathway.

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