Procyanidin biosynthesis

There is no final consensus on whether procyanidin biosynthesis is controlled thermodynamically or enzymatically. In either case proanthocyanidins are synthesized through sequential addition of flavan-3,4-diol units (in their reactive forms as carbocations or quinone methides) to a flavan-3-ol monomer [218]. Based on the latest findings there is some evidence that different condensation enzymes might exist which are specific for each type of flavan-3,4-diol [64] and that polymer synthesis would be subject to a very complex regulatory mechanism [63]. But so far, no enzyme synthetase systems have been isolated and enzymatic conversion of flavanols to proanthocyanidins could not be demonstrated in vitro [219]. If biosynthesis was thermodynamically controlled, the variation in proanthocyanidin composition could be explained by synthesis at different times or in different compartments [64], The hypothesis of a thermodynamically controlled biosynthesis is based on the fact that naturally and chemically synthesized procyanidin dimers occur as a mixture of 4—>8 and 4—>6 linked isomers in approximate ratios of 3-4 1 [220]. Porter [164] found analogous ratios of 4—>8 and 4—>6 linkages in proanthocyanidin polymers. 

Stafford H A 1983 Enzymic regulation of procyanidin biosynthesis Lack of a flav-3-en-3-ol intermediate. Phytochemistry 22 2643-2646... 

The above observations tend to suggest that more than one metabolic pool for the production of proanthocyanidins may exist in a plant and these in some cases are localized in different tissues. There is some evidence for this in Stafford s observations on procyanidin biosynthesis in Douglas-fir callus tissue (130, 131). Here quite high concentrations of dimers and trimers based on catechin-4 (5) units are found, but the associated polymer is based almost entirely on epi-catechin-4 (2) units, and evidence was obtained that the latter are formed much more rapidly than the catechin-4 oligomers (131). Thus the main biosynthetic process appears to be directed towards the synthesis of epicatechin-4 units that are diverted to polymers, and it seems likely that the two types of unit may be derived from distinct metabolic pools. 

Proanthocyanidins and Procyanidins - In a classical study Bate-Smith ( ) used the patterns of distribution of the three principal classes of phenolic metabolites, which are found in the leaves of plants, as a basis for classification. The biosynthesis of these phenols - (i) proanthocyanidins (ii) glycosylated flavonols and (iii) hydroxycinnamoyl esters - is believed to be associated with the development in plants of the capacity to synthesise the structural polymer lignin by the diversion from protein synthesis of the amino-acids L-phenylalanine and L-tyro-sine. Vascular plants thus employ one or more of the p-hydroxy-cinnarayl alcohols (2,3, and 4), which are derived by enzymic reduction (NADH) of the coenzyme A esters of the corresponding hydroxycinnamic acids, as precursors to lignin. The same coenzyme A esters also form the points of biosynthetic departure for the three groups of phenolic metabolites (i, ii, iii), Figure 1. 

Earlier proposals (12, 13, U) and the results of biosynthetic experiments (18) have been adumbrated into a scheme of biosynthesis for the procyanidins (Figure k) in which it is suggested that they are formed as byproducts during the final stage of the synthesis of the parent flavan-3-ol structures, (+)-catechin and (-)-epicatechin (11, 18). A two step reduction of the f1av-3-en-3-ol... 

Camesecchi, S. Schneider, Y. Lazarus, S.A. Coehlo, D. Gosse, F. Raul, F. 2002. Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells. Cancer Lett. 175 147-155. 

Whether biosynthesis is enzymatically or thermodynamically driven, naturally occurring procyanidins in either case display a multitude of structural diversity of various degrees of polymerization, which is simply beyond the separating capacity of any chromatographic system. Nevertheless, all classical chromatographic procedures have been applied to procyanidin analysis. Some reviews on the chromatography of procyanidins are also available [26,107,221-222],... 

Treatment of Caco-2 cells with 50 pg/ml of procyanidin-emiched (PE) extracts from cocoa caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ODC and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis, which might be an important target in the antiproliferative effects of cocoa polyphenols. ... 

Details about structure, biosynthesis, and classification of phenolics are described in the other chapters in this handbook. Plant phenolics have a distinctive ability to form non-covalent, intermolecular complexes with each other and with both large and small molecules. Recognition of the antioxidant activities of many polyphenols has established correlation with the health benefits by such compounds [34]. This leads to the development of commercial products containing free-radical-scavenging phytochemical mixtures, for example, Pycnogenol (procyanidin extracted from Pinus maritima). Table 82.2 represents a list of polyphenolic compounds used in nutraceuticals and their biologic effects on human health. 

Jacques D, Opie C T, Porter L J, Haslam E 1977 Plant proanthocyanidins. Part 4. Biosynthesis of procyanidins and observations on the metabolism of cyanidin in plants. J Chem Soc Perkin Trans I 1637-1643... 

Kristiansen K N 1984 Biosynthesis of proanthocyanidins in barley Genetic control of the conversion of dihydroquercetin to catechin and procyanidins. Carlsberg Res Commun 49 503-524... 

Fig. 7.7.6. Biosynthesis of procyanidins through a flavan-3,4-diol intermediate. The bottom four diol and flavan-3-ol units react together to form procyanidin oligomers and polymers...

Analogous schemes, with some variations, may be used to accommodate the biosynthesis of esters and glycosides of caffeic acid, quercetin and hence the procyanidins (1, R = H). However several serious uncertainties arise when the origin of flavonoids such as myricetin and the prodelphinidins (1, R = OH) is considered. 3,4,5-Trihydroxycinnamic acid (5) is not an intermediate in lignin synthesis and, except as its various o-methyl ethers, it has not been encountered in nature. Its role as a putative precursor of the vicinal trihydroxyaryl (pyrogallol) group in... 

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