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

Stoichiometry and Energetics of Metabolic Conversions
Biosynthesis
Synthesis of Macromolecular Compounds

As shown in the general metabolic pathway map in the Introduction to this chapter, the polymeric Components of the Cell must be subsequently built from monomeric precursor molecules. This process again requires a large amount of metabolic energy, since any Condensation reaction is accompanied by an increase in Free energy. Furthermore, exceptionally large stores of free energy act as the driving force that strongly shifts the overall equilibrium toward The formation of the required polymers. This is particularly crucial in The Biosynthesis of polymers with strictly defined structures, such as Nucleic Acids and Proteins with specific sequences.

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FIG. 5.15. Simplified scheme of glucose synthesis from CO₂ in The Calvin Cycle.

As illustrated in Fig. 5.16, the energy stored in the phosphate bonds of ATP is utilized in the biosynthesis of four classes of Biopolymers through the intermediacy of other nucleotide triphosphates. A typical feature of macromolecular biosynthesis is the coupling of a condensation reaction with the Hydrolysis of two high-energy phosphate bonds. First, a nucleoside triphosphate is converted into a nucleoside monophosphate and pyrophosphate, which subsequently undergoes hydrolysis. This pathway releases approximately twice as much free energy (about 14 kcal/mol) as The conversion of a nucleoside triphosphate into the corresponding diphosphate. Variations of this general mechanism operate in the biosynthesis of Lipids, RNA, DNA, and Glycogen.

Here again, THE PRINCIPLE OF common intermediates is employed, albeit in a somewhat more complex form. For example, The addition of a glucose residue to a growing glycogen molecule proceeds in six stages, four of which are sequential and, consequently, linked by common intermediates (Table 5.5).

FIG. 5.16. Participation of high-energy nucleoside triphosphates in various biosynthetic pathways. (Reprinted by permission from: Lehninger A., Bioenergetics, 2d ed., p. 136, W. A. Benjamin, Inc., Palo Alto, 1975.)

Naturally, the synthesis of informational polymers (RNA, DNA, and proteins) is a considerably more complex process. In both cases, however, the elongation of the polymer chain is preceded by monomer activation. NUCLEOTIDES enter the synthesis of RNA and DNA in the form of nucleoside triphosphates, whereas the monophosphate is attached to the corresponding polymer chain, with the reaction accompanied by the release of pyrophosphate. Thus, the incorporation of a single monomeric residue requires an expenditure of 14 kcal/mol of energy. The activation of Amino Acids during Protein Synthesis proceeds According to the following scheme:

In addition, the attachment of The amino acid adenylate to the peptide chain is coupled with the hydrolysis of GTP; consequently, the incorporation of a single amino acid residue into a protein chain requires the hydrolysis of a total of three high-energy phosphate bonds. In Chapter 6, we will examine the mechanisms governing the biosynthesis of specific sequences of monomeric units in DNA, RNA, and proteins.

Table 5.5. Sequential Stages of glycogen biosynthesis in mammalian Cells (in Bacteria and plants, ATP-Glucose is formed as an intermediate instead of UDP-glucose)^a

^a Reprinted from: Lehninger A. L., Bioenergetics, 2d ed., p. 140, W. A. Benjamin, Inc., Palo Alto, Ca., 1971.