Glucose biosynthesis from amino acids

Pyruvic acid is important as an intermediate in sugar metabolism. This acid is formed as the final product of the glycolytic pathway from 3-phosphoglycerate via phosphoenolpyruvate. Pyruvic acid is also formed through the oxidative pentose phosphate cycle. The degradation of glucose in the cycle yields the C3 product glyceraldehyde 3-phosphate, which can be oxidized to pyruvate. Pyruvic acid is the principal precursor for the biosynthesis of amino acids such as alanine, as well as leucine and valine. 

Pyridoxine is involved as a co-factor coenzyme in about 100 enzyme systems. Thus, in addition to the reactions mentioned above, it is required for glycogen phosphoryl-ase, which catalyses the release of glucose from stored glycogen, haemoglobin biosynthesis, the generation of glucose from amino acids (gluconeogenesis), the biosynthesis of niacin from tryptophan and nucleic add biosynthesis. 

From tables of standard free energies of formation, we find AG,° = -2885 kj-mol-1. Therefore, the maximum nonexpansion work obtainable from 1.00 mol C6H1206(s) is 2.88 X 103 kj. About 17 kj of work must be done to build 1 mol of peptide links (a link between amino acids) in a protein, so the oxidation of 1 mol (180 g) of glucose can be used to build up to about 170 mol of such links. More visually the oxidation of one glucose molecule is needed to build about 170 peptide links. In practice, biosynthesis occurs indirectly, there are energy losses, and only about 10 such links can be built. A typical protein has several hundred peptide links, so several dozen glucose molecules must be sacrificed to build one protein molecule. 

The biosynthesis of fatty acids occurs extramitochondrially and by a set of enzymes that are different from those of fatty acid degradation. Nevertheless, both processes may involve the same, although not exchangeable, intermediates. Acetyl-CoA forms the building blocks of the newly synthesized fatty acid. It may be derived from glucose, amino acids, or ethanol. 

Microbes and plants synthesize aromatic compounds to meet their needs of aromatic amino acids (L-Phe, L-Tyr and L-Trp) and vitamins. The biosynthesis of these aromatics [69] starts with the aldol reaction of D-erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), which are both derived from glucose via the central metabolism, into DAHP (see Fig. 8.13). DAHP is subsequently converted, via a number of enzymatic steps, into shikimate (SA) and eventually into chorismate (CHA, see later), which is the common intermediate in the biosynthesis of the aromatic amino acids [70] and vitamins. 

The biosynthetic pathway from SA into L-Phe [69, 70] is shown in Fig. 8.15. The synthesis of chorismate (CHA), the common intermediate in the biosynthesis of the aromatic amino acids, requires an extra equivalent of PEP, which limits the yield of L-Phe from glucose to 0.30 mol mol-1 if PEP is not conserved [91]. The further transformation of CHA into phenylpyruvic acid (PPY) suffers from inhibition by L-Phe and is also subject to transcriptional control [69, 92]. The final step is a reductive amination of PPY into L-Phe with consumption of l-G1u. 

Various inborn errors of metabolism (Table 25-1) result from deficiencies or absence of some of the enzymes listed in Figure 25-9. Some of these are discussed later in the chapter. The relationship of carbohydrate metabolism to the production of lactate, ketone bodies, and triglycerides is also depicted in Figure 25-9. The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative pathway for glucose metaboUsm that generates the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), which is used in maintaining the integrity of red blood cell membranes, in lipid and steroid biosynthesis, in hydroxylation reactions, and in other anabolic reactions. The complete picture of intermediary metabolism of carbohydrates is rather complex and interwoven with the metabolism of lipids and amino acids. For details, readers should consult a biochemistry textbook. 

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