Synthesis from glucose

Liquid Polyols from Glucose Synthesis and Characterization. Liquid polyols were prepared from a-D-glucose (1) and the aglycon, a PTHF diol (2), by acid-catalyzed reactions under nitrogen at 130 °C in N-methyl pyrrolidone, NMP, solutions ( -0). 

M.p. 190-192 C. The enolic form of 3-oxo-L-gulofuranolactone. It can be prepared by synthesis from glucose, or extracted from plant sources such as rose hips, blackcurrants or citrus fruits. Easily oxidized. It is essential for the formation of collagen and intercellular material, bone and teeth, and for the healing of wounds. It is used in the treatment of scurvy. Man is one of the few mammals unable to manufacture ascorbic acid in his liver. Used as a photographic developing agent in alkaline solution. 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Succinyl-CoA derived from propionyl-CoA can enter the TCA cycle. Oxidation of succinate to oxaloacetate provides a substrate for glucose synthesis. Thus, although the acetate units produced in /3-oxidation cannot be utilized in glu-coneogenesis by animals, the occasional propionate produced from oxidation of odd-carbon fatty acids can be used for sugar synthesis. Alternatively, succinate introduced to the TCA cycle from odd-carbon fatty acid oxidation may be oxidized to COg. However, all of the 4-carbon intermediates in the TCA cycle are regenerated in the cycle and thus should be viewed as catalytic species. Net consumption of succinyl-CoA thus does not occur directly in the TCA cycle. Rather, the succinyl-CoA generated from /3-oxidation of odd-carbon fatty acids must be converted to pyruvate and then to acetyl-CoA (which is completely oxidized in the TCA cycle). To follow this latter route, succinyl-CoA entering the TCA cycle must be first converted to malate in the usual way, and then transported from the mitochondrial matrix to the cytosol, where it is oxida-... 

Table V indicates the incorporation and distribution of labeled compounds into kasugamycin (1), when they are added during the production of this antibiotic. Glucose is incorporated into kasugamine and d-inositol. Mt/o-inositol is mainly incorporated into the d-inositol moiety, suggesting the synthesis of d-inositol moiety through myo-inositol or its derivative from glucose or other carbon sources.

Figure 20.7 The industrial synthesis of ascorbic acid from glucose.

Figure 16-5. Participation of the citric acid cycle in fatty acid synthesis from glucose. See also Figure 21-5.

Scheme 6.15 Synthesis of adipic acid from glucose using E. coli...

The Jirst indirect route in glucose synthesis involves the formation of phosphoenolpyruvate from pyruvate without the intervention of pyruvate kinase. This route is catalyzed by two enzymes. At first, pyruvate is converted into oxaloacetate. This reaction occurs in the mitochondria as the pyruvate molecules enter them, and is catalyzed by pyruvate carboxylase according to the scheme... 

If the synthesis starts from glucose molecules, then the initial step is the transfer of glucose residues from UDP-glucose onto an intermediary acceptor-dolichol phosphate (membrane-bound polyprenol phosphate). Dolichol phosphate assists in the synthesis of an... 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

The main question is whether synthesis of PHA in plants can succeed in bringing the cost of the polymer down to the range of 0.5 -1 US /kg. Bacterial production of PHA typically relies on a carbon source, such as sucrose or glucose, which is produced from photosynthesis and extracted from plants. Synthesis of PHA directly in plants would, therefore, represent a saving in terms of the number of intermediary steps linking C02 fixation to PHA production. Furthermore, starch is one of the cheapest plant commodity product on the market, at about 0.25 US /kg [86]. It is, thus, likely that the production cost of PHA in plants will be substantially cheaper than bacterial fermentation. The final cost of producing PHA in plants will depend on a number of factors. 

The acetyl CoA used for ACh synthesis in mammalian brain comes from pyruvate formed from glucose. It is unclear how the acetyl CoA, generally thought to be formed at the inner membrane of the mitochondria, accesses the cytoplasmic ChAT. This may also be a regulated, rate-limiting step. 

Dioxalicyclo[3.2.1]octane, or (+)-exo-brevicomin (66), is the aggregating pheromone of the western pine beetle. It has been prepared from glucose using a procedure based on the retro synthesis design shown in Figure 1-2884 ... 

An impressive one-pot six-step enzymatic synthesis of riboflavine from glucose on the laboratory scale has been reported with an overall yield of 35-50%. Six different enzymes are involved in the various synthesis steps, while two other enzymes take care for the in situ cofactor regenerations [12]. This example again shows that many more multi-enzyme cascade conversions will be developed in the near future, as a much greater variety of enzymes in sufficient amounts for organic synthetic purposes will become available through rapid developments in genomics and proteomics. 

In common with cholesterol synthesis described in the next section, fatty acids are derived from glucose-derived acetyl-CoA. In the fed state when glucose is plentiful and more than sufficient acetyl-CoA is available to supply the TCA cycle, carbon atoms are transported out of the mitochondrion as citrate (Figure 6.8). Once in the cytosol, citrate lyase forms acetyl-CoA and oxaloacetate (OAA) from the citrate. The OAA cannot re-enter the mitochondrion but is converted into malate by cytosolic malate dehydrogenase (cMDH) and then back into OAA by mitochondrial MDH (mMDH) Acetyl-CoA remains in the cytosol and is available for fatty acid synthesis. 

---