Dehydroquinate

Some biochemical processes involve alcohol dehydration as a key step. An exanple is the conversion of a compound called 3-dehydroquinic acid to 3-dehydroshikimic acid. 

Dehydroquinic acid and [l,6-14C]-D-shikimic acid methyl ester were not incorporated, indicating a very early branch from the shikimate pathway. The intermediacy of 4-amino-3,4-dideoxy-D-araf>ino-heptulosonic acid 7-phosphate (37) was proposed, consistent with later findings on the role of the variant aminoshikimate pathway [94]. 

This enzyme [EC 4.2.1.10] catalyzes the reaction of 3-dehydroquinate to produce 3-dehydroshikimate and water. 

This enzyme [EC 4.6.1.3] catalyzes the conversion of 3-deoxy-(2raZ mo-heptulosonate 7-phosphate to form 3-dehydroquinate and orthophosphate. The enzyme requires cobalt and the hydrogen atoms located on C7 of the substrate are retained on C2 of the product. 

CELLOBIOSE PHOSPHORYLASE CHORISMATE SYNTHASE COBALAMIN ADENOSYLTRANSFERASE 3-DEHYDROQUINATE SYNTHASE... 

The shikimate pathway begins with a coupling of phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate to give the seven-carbon 3-deoxy-D-arabino-heptulo-sonic acid 7-phosphate (DAHP) through an aldol-type condensation. Elimination of phosphoric acid from DAHP, followed by an intramolecular aldol reaction, generates the first carbocyclic intermediate, 3-dehydroquinic acid. Shikimic acid (394) is... 

Figure 3. Hypothetical alternative enzyme path between 3-dehydroquinate and shikimate. A reversed order of the dehydratase and dehydrogenase steps of the classical pathway (top) would produce the quinate route (bottom).

Inhibition of Dehydroquinase Type II Dehydroquinase type II is an important enzyme in the shikimic and quinic routes. It ensures the reversible conversion of 3-dehydroquinate (DHQ) into 3-dehydroshrkimate (DHS). Ehmination of the hydroxyl is assisted by an acid/base catalysis that is associated with a residue of the active site. 

The enolate involved in the conversion of 3-dehydroquinate into 3-dehydroshiki-mate can be sterically and electronically mimicked by a vinyl fluoride. However, the ketonization process is impossible. This vinyl fluoride is a competitive inhibitor of dehydroquinase II that is 20 times more powerful than the nonfluorinated analogue (Figure 7.7). Moreover, it is very selective toward dehydroquinase I, whUe it acts according to a different mechanism. ... 

The product of the DAHP synthase, 3-deoxy-D-arabino-heptulosonate 7-phosphate, is shown in its cyclic hemiacetal form at the beginning of Eq. 25-2. Its conversion to 3-dehydroquinate is a multistep process that is catalyzed by a single enzyme, 14/15 which is the product of E. coli gene am B. The elimination of... 

Dehydration of 3-dehydroquinate (step c), the first step in Eq. 25-3, is the first of three elimination reactions needed to generate the benzene ring of the end products. This dehydration is facilitated by the presence of the carbonyl group. After reduction of the product to shikimate (step d)19 a phosphorylation reaction (step e)20,21 sets the stage for the future elimination of Pj. In step/, condensation with PEP adds three carbon atoms that will become the a, P, and... 

Quinic acid, a compound accumulated by many green plants, can be formed by reduction of 3-dehy-droquinate (Eq. 25-2) in both plants and bacteria. Quinic acid can be converted into useful industrial products such as benzoquinone and hydroquinone, and its production by bacteria provides a convenient route to these compounds.168 In the main shikimate pathway 3-dehydroquinate is dehydrated to 3-dehydroshikimate (Eq. 25-3). The latter can be dehydrated... 

The shikimate pathway is common to both plants and microorganisms (Figure 3-3). Shikimate is synthesized from the substrates phosphoewo/pyruvate (3.9) and erythrose 4-phosphate (3.17). These two precursors are derived from glycolysis and the pentose phosphate pathway, respectively, and are condensed to 3-deoxy-D-ara6/ o-heptulosonate 7-phosphate (DAHP 3.18) by the enzyme DAHP synthase. The subsequent steps result in the formation of 3-dehydro-quinate (3.19) by the enzyme 3-dehydroquinate synthase, 3-dehydroshikimate... 

S. L. Rotenberg and D. B. Sprinson, Isotope effects in 3-dehydroquinate synthase and dehydratase. Mechanistic implications, J. Biol. Chem., 253 (1978) 2210-2215. 

FIGURE 3.2 The common aromatic pathway to chorismate in Escherichia coli K12, where 5 is phosphoe-nolpyruvate, 6 is erythrose 4-phosphate, 7 is 3-deoxy-D-arabinoheptulose 7-phosphate, 8 is 3-dehydroquinic acid, 9 is 3-dehydroshikimic acid, 10 is shikimic acid, 11 is shikimic acid 3-phosphate, and 12 is 5-enolpyru-vylshikimic acid 3-phosphate. 

---