Quinic acid metabolism

The bacterium Klebsiella pneumonia can use quinic acid as a carbon source for its growth the first step here is oxidation of quinic acid to 3-deoxyhydroquinate (DHQ), which is catalyzed by the enzyme quinic acid dehydrogenase. Actually, thermodynamics predicts that the reverse reaction is favored. So if a second bacterium, which made DHQ, had inserted into it the gene for the dehydrogenase, and if this second bacterim did not normally metabolize quinic acid, then this would result in the second organism synthesizing quinic acid from DHQ. 

Accordingly, a strain of E. coli was first engineered to produce elevated levels of DHQ by increasing the levels of certain key enzymes transketolase, 3-deoxy-D-arabino-heptulosonic acid 7-phospate (DAHP) synthase, and DHQ synthase. Also, the strain has reduced levels of DHQ dehydratase, which if present would divert some of the metabolic flow into the biosynthesis of aromatic amino acids its blockage results in higher production of quinic acid. 

We comprehensively summarized chlorogenic acids and related compounds in absorption, metabolism and biological activity. Chlorogenic, caffeic and quinic acids are well absorbed in humans and rats. Metabolic transformations of chlorogenic acids in the human system may be crucial for their biological effect. 

In the 1950s, it has been reported that chlorogenic acid is invariably found in cider apple juices [19]. In some varieties, it may constitute more than 0.25% (w/v) of the juice. Lactobacillus hydrolyzes chlorogenic acid to caffeic acid and quinic acid during cider fermentation [19]. Both of these acids are then further metabolized by Lactobacillus. 

Quinic acid is metabolized to aromatic substances by gut flora when ingested by animals. However, the microorganisms responsible have not been identified. Species difference of aromatization of quinic acid may be related to gut flora. 

Caffeic acid derivatives Caffeic acid (110), Chloro-genic acid (111) its butyl ester, Rosmarinic acid (112), KOP (Caffeic acid oxidised polymer). 3,4,5-Tri-O-caffeoyl-quinic acid, 4,5-Di-O -caffeoylquinic acid, Synapoic acid Many sp. Securidaca longipedunculala HSV HIV Virucidal, Cellular DNA metabolism. Binding of gpl20 to CD4 HIV-RT [16. 73, 74] [75, 76]... 

The role of quinic acid in the shikimic acid pathway is not understood. In some plants, compared with shikimate, quinate administered exogenously is more effectively incorporated into the aromatic amino acids. These results have been interpreted to mean that quinate occurs on the pathway of aromatic amino acid synthesis and is not a shunt metabolite as depicted in Fig. 2. Different routes of metabolism for quinate and shikimate are also suggested by other experiments. For example, when p CJglucose and [ C]ery-throse are compared for eflSciency of their conversion into shikimate and... 

Fio. 4. Reactions in the aromatic synthetic and quinic acid catabolic pathways, indicating the metabolic relationships of the two dehydroquinase isozymes in Neurospora crassa [60]. 

Dehydoquinic acid is also synthesized in a sequence of enzymatically catalysed reactions from phosphoenolpyruvate and D-erythrose-4-phosphate which are both activated intermediates from the carbohydrate metabolism. As an unusual intermediate 3-dehydro-D-arabo-heptalose-7-phosphate (DAHP), a sugar containing 7 carbon atoms, is formed. After enzymatic condensation by DAHP-synthase followed by a dephosphorylation step, 3-dehydro-quinic acid is obtained and further transformed to 3-dehydroshikimic acid as shown above. 

During the elucidation of the aromatic biosynthetic pathway, compounds were found that appear to be made in side reactions. These include quinic acid, which is reversibly made from dehydroquinic acid through the action of a DPN-specific dehydrogenase. This enzyme is found in Aerobacter, but not in E. coli. 5-Phosphoshikimic acid is also accumulated by certain coli mutants, but has no known metabolic func-... 

Quinic acid, a carboxylated tetrahydroxycyclohexane, is a secondary plant substance formed from dehydroquinic acid, an intermediate in the shikimic acid pathway, the metabolic pathway leading to aromatic compounds. It, therefore, is ubiquitous in living plant cells. It has been isolated from cinchona bark and detected in the cambial sap of conifers (114). 

The most cautionary examples of selective metabolisms are those in which man behaves differently from most other mammals, for herein lies one of the dangers in transferring results from laboratory animals to man. Here are some examples. The only animals that dehydrogenate quinic acid to benzoic acid are man and the Old World primates, for not even the New World primates do so. The antibacterial sulphonamide sulpha-dimethoxine is excreted by man and the primates as the N -glucuronide, whereas the common laboratory animals excrete it as the AT-acetyl-derivative (Adamson, Bridges and Williams, 1966). Other aromatic amines such as aniline and sulphanilamide are acetylated in man, and many other mammals, as well as in most species of birds, amphibia, reptiles, and fish nevertheless dogs, frogs and turtles do not perform acetylation. Further examples of different metabolic paths followed by man on the one hand and mammals on the other have been traced for amphetamine, phenylacetic acid, and 6-propylthiopurine in Section 3.4 (p. 82). 

An example of process optimization by metabolic engineering is the production of intermediates for the synthesis of oseltamivir. This neuraminidase inhibitory drug (Tamiflu ) acts against the common as well as the threatening asian flu. Quinic and shikimic acid can serve as precursors (Scheme 4.20A), but the shiki-... 

Boudet A, Gadal P, Alibert G, Marigo G 1967 Biosynthesis and metabolism of aromatic compounds in higher plants. Demonstration of the alicyclic precursors quinic, 5-dehydroquinic, shikimic, and 5-dehydroshikimic acids in Quercus pedunculata. C R Acad Sci 265 119-122... 

MARTIN A.K. 1982a. The origin of urinary aromatic compounds excreted by ruminants 1. The metabolism of quinic, cyclohexanecarboxylic and non-phenolic aromatic acids to benzoic acid. British Journal of Nutrition, 47, 139-154. 

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