Caffeic acid phenylpropanoid

Hydroxy cinnamic acids are included in the phenylpropanoid group (C6-C3). They are formed with an aromatic ring and a three-carbon chain. There are four basic structures the coumaric acids, caffeic acids, ferulic acids, and sinapic acids. In nature, they are usually associated with other compounds such as chlorogenic acid, which is the link between caffeic acid and quinic acid. 

Simple phenolic compounds include (1) the phenylpropanoids, trans-cinnamic acid, p-coumaric acid and their derivatives (2) the phenylpropanoid lactones called coumarins (Fig. 3.4) and (3) benzoic acid derivatives in which two carbons have been cleaved from the three carbon side chain (Fig. 3.2). More complex molecules are elaborated by additions to these basic carbon skeletons. For example, the addition of quinic acid to caffeic acid produces chlorogenic acid, which accumulates in cut lettuce and contributes to tissue browning (Fig. 3.5). 

The 4-coumarate CoA ligase (4CL EC 6.2.1.12) enzyme activates 4-coumaric acid, caffeic acid, ferrulic acid, and (in some cases) sinapic acid by the formation of CoA esters that serve as branch-point metabolites between the phenylpropanoid pathway and the synthesis of secondary metabolites [46, 47]. The reaction has an absolute requirement for Mg " and ATP as cofactors. Multiple isozymes are present in all plants where it has been studied, some of which have variable substrate specificities consistent with a potential role in controlling accumulation of secondary metabolite end-products. Examination of a navel orange EST database (CitEST) for flavonoid biosynthetic genes resulted in the identification of 10 tentative consensus sequences that potentially represent a multi-enzyme family [29]. Eurther biochemical characterization will be necessary to establish whether these genes have 4CL activity and, if so, whether preferential substrate usage is observed. 

The chemical and physical evidence for the presence of lignin in the material deposited at wound margins is supported by biochemical studies on the enzymes involved in phenylpropanoid metabolism. Thus, the extractable activities of phenylalanine ammonia-lyase, tyrosine ammonia-lyase, cinnamate-4-hydroxylase, caffeic acid O-methyltransferase,... 

Several simple non-volatile phenylpropanoids are known to be allelochemics. Among these are -coumaric acid, ci and trans-caffeic acid (17), chlorogenic acid, and a caffeyl derivative of an aldaric acid (97). 

Phenylpropanes are aromatic compounds with a propyl side chain attached to the benzene ring, which can be derived directly from phenylalanine. Naturally occurring phenylpropanoids often contain oxygenated substituents, e.g. OH, OMe or methylenedioxy, on the benzene ring. Phenylpropanoids with hydroxyl substituent(s) on the benzene ring belongs to the group of phenolics, e.g. caffeic acid and coumaric acid. 

Phenylpropanoid biosynthesis gives rise to caffeic acid, lignins,... 

As discussed in Section 7, the general phenylpropanoid pathway originally included the biosynthesis of the hydroxycinnamic acids caffeic acid (3.32), femlic acid (3.33), 5-hydroxyferulic acid (3.34), and sinapic acid (3.35) from />coumaric acid (3.30), as well as the corresponding CoA-esters... 

MAURY, S., GEOFFROY, P., LEGRAND, M., Tobacco O-methyltransferases involved in phenylpropanoid metabolism. The different caffeoyl-coenzyme A/5-hydroxyferuloyl-coenzyme A 3/5-O-methy (transferase and caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferase classes have distinct substrate specificities and expression patterns., Plant Physiol., 1999,121,215-223. 

Phenylpropanoids have an aromatic ring with a three-carbon substituent. Caffeic acid (308) and eugenol (309) are known examples of this class of compounds. Phenylpropanoids are formed via the shikimic acid biosynthetic pathway via phenylalanine or tyrosine with cinnamic acid as an important intermediate. Phenylpropanoids are a diverse group of secondary plant compounds and include the flavonoids (plant-derived dyes), lignin, coumarins, and many small phenolic molecules. They are known to act as feeding deterrents, contributing bitter or astringent properties to plants such as lemons and tea. 

Lithospermic acid (phenylpropanoid, caffeic acid trimer, benzofuran)... 

Hydroxycinnamic acids possess a C6-C3 skeleton and formally belong to the group of phenylpropanoids. The different compounds present in wine are mainly derived from the hydroxycinnamic acids caffeic acid, p-coumaric acid, ferulic acid, and sinapic acid (Fig. 9C.2). These derivatives can be present in cis- and trans-configured forms, while the trans forms are more stable and therefore more prevalent. In wine HCA are present in low amounts in their free form, while the depside forms, i.e. esters of l-(-i-)-tartaric acid, are predominant. The ubiquitous chlorogenic acids, esters of HCA and quinic acid, cannot be found in wine but are replaced by the tartaric acid esters instead (Ong and Nagel 1978 Singleton et al. 1978 Somers etal. 1987). 

Figure 4 Current view of the phenylpropanoid pathway to the monolignols 19-23. 4CL, 4-hydroxycinnamate coenzyme Aligases pC3H , p-coumarate 3-hydroxylase C4H, cinnamate 4-hydroxylase CAD, cinnamyl alcohol dehydrogenases CCOMT, hydroxycinnamoyl CoA O-methyltransferases CCR, cinnamoyl-CoA oxidoreductases COMT, caffeic acid O-methyltransferases F5H , ferulate 5-hydroxylase HCT, hydroxycinnamoyl-CoA shikimate hydroxycinnamoyltransferase HOT, hydroxycinnamoyl-CoA quinate hydroxycinnamoyltransferase PAL, phenylalanine ammonia lyase TAL, tyrosine ammonia lyase.

Lignans are dimers of phenylpropanoid units linked by the central carbons of their side chains while naturally occurring dimers that exhibit linkages other than this type of bond are known as neolignans. Much attentions has been devoted to the oxidative, acidic or alkaline dimerisations of arylpropenoid molecules and particularly 4-hydroxycinnamic acids such as ferulic and caffeic acids [24-34]. 

Phenolic compounds include a wide range of secondary metabolites that are biosynthesised from carbohydrates through the shikimate pathway [14]. This is the biosynthetic route to the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, and only occurs in microorganisms and plants. In the first step, the glycolytic intermediate phosphoenol pyruvate and the pentose phosphate intermediate erythrose-4-phosphate are condensed to 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), a step catalysed by DAHP synthase. Intermediates of the shikimate pathway are 3-dehydroquinate, shikimate, and chorismate (Fig. 1). Phenylalanine is biosynthesised from chorismate, and from phenylalanine all the phenylpropanoids. Quinate is produced from 3-dehydroquinate and incorporated into chlorogenic and isochlorogenic acids (caffeoyl quinic acids) by combination with caffeic acid. Gallic acid is produced from shikimate. 

Figure 3.1 Primary flux of carbon through phenylpropanoid pathway in Arabidopsis. PAL, phenylalanine ammonia-lyase 4CL, 4-(hydroxy)cinnamoyl CoA ligase C4H, cinnamate 4-hydroxylase HCT, hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyltransferase C3 H, /7-coumaroylshikimate 3 -hydroxylase CCoAOMT, caffeoyl CoA O-methyltransferase F5H, ferulate 5-hydroxylase COMT, caffeic acid/5-hydroxyferulic acid o-methyltransferase CCR, cinnamoyl CoA reductase CAD, cinnamyl alcohol dehydrogenase. Not depicted is the HCT catalyzed synthesis of/r-coumaroyl quinate.

Fig. 10. The pathway of aromatic biosynthesis in the cytosol and its point of interface with phenylpropanoid biosynthesis at the reaction catalyzed by phenylalanine ammonia-lyase (PAL). Enzymes sensitive to inhibition by caffeic acid (CAF) are indicated by dark shading. Abbreviations as in Figure 9 additionally, GIN, cinnamic acid COU, coumaric acid.

Scheme 12.22. A representation of the deamination of phenylalanine (Phe,F) to (F)-cinnamic acid and the conversion of the latter into more highly oxidized derivatives. The caffeic acid and ferulic acid serve as introductory compounds to phenylpropanoids. EC numbers and some graphic materials provided in this scheme have been taken from appropriate links in a URL starting with http //www.chem.qmul.ac.uk/iubmb/enzyme/.

In a similar study, different phenylpropanoid acids, such as cinnamic acid (32), p-coumaric acid (33), caffeic acid (34), and ferulic acid (35), were fed to recombinant yeast containing four different initial flavanone biosynthetic plant genes, C4H, 4CL, CHS, and CHI, at different time intervals to produce flavanones. In cinnamic acid-supplemented culture, 16.3 mg 1 of pinocembrin (31) and 0.2 mg 1 of naringenin (30) were produced. Naringenin (28.3 mg 1 ) and (2S)-eriodictyol (6.5 mg 1 ) were detected in p-coumaric acid- and caffeic acid-supplemented cultures, respectively. No flavanones were produced with ferulic acid precursor substrate [33]. The production of pinocembrin and naringenin in S. cerevisiae was 22- and 62-fold higher compared to that of respective flavanones in E. coli [34]. 

Phenylpropanoids, which display a Cs-Cs arrangement, are frequently, but not always, phenolic compounds. From a biosynthetic point of view, these compounds derive from phenylalanine and tyrosine and some examples are ferulic, cinnamic, caffeic acids, among others. 

Esters of 3a-Hydro tropane/-4tortropaiie with Phenylpropanoid Acids (T5). This group of metabolites is a small one with hydroxycinnamic acids as acyl components, i.e., caffeic acid, femlic add, sinapic acid. It is also a rather rarely occurring group (six genera, 12 spedes = 7% of all species checked). Such alkaloids could be... 

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