Metabolic grids

As briefly described above, proposed biosynthetic pathways to the monolignols follow a metabolic grid, with a number of parallel and redundant pathways for the synthesis of the major lignin components, namely guaiacyl and syringyl units. Currently, the methylation steps in the lignin biosynthetic pathway are believed to follow two main branches dependent on COMT and CCoAOMT,... 

Dixon, R.A., Ghen, R, Guo, D. and Parvathi, K. (2001) The biosynthesis of monolignols a metabolic grid, or independent pathways to guaiacyl and syringyl units Phytochemistry, 57,1069-84. 

In the early stages of the biosynthesis of agroclavine (7) and elymoclavine (8) a metabolic grid appears to operate. Dimethylallyltryptamine (9) and its... 

Quinolizidine Alkaloids.—Previous results demonstrate that the quinolizidine skeleton in its entirety derives from lysine.Further research has indicated that lysine is a precursor of all the alkaloids of this type in five species of Leguminosae. From the levels of activity observed in the individual alkaloids it was concluded that saturated alkaloids are precursors for those with a pyridone ring. This was supported by the observation that label from radioactive sparteine (24) and lupanine (25) appeared in more highly oxidized alkaloids. (This compares with a similar situation in the biosynthesis of matrine-type alkaloids. ) A metabolic grid for the biosynthesis of quinolizidine alkaloids from lysine was proposed, based on these results,... 

The pathways shown in Fig. 2 are a composite from work with many different species and tissues. They compose a metabolic grid resulting from 7-oxidase, 13-hydroxylase,... 

YABE, K., CHIHAYA, N., HAMAMATSU, S., SAKUNO, E., HAMASAKI, T., NAKAJIMA, H., BENNETT, J.W., Enzymatic conversion of averufin to hydroxyversicolorone and elucidation of a novel metabolic grid involved in aflatoxin biosynthesis, Appl Environ. Microbiol, 2003, 69, 66-73. 

YABE, K., ANDO, Y., HAMASAKI, T., A metabolic grid among versiconal hemiacetal acetate, versiconol acetate, versiconol and versiconal during aflatoxin biosynthesis, y. Gen. Microbiol., 1991,137, 2469-2475. 

The sequence of the hydroxylation and esterification steps in Myrothecium spp. fermentations between trichodermol (110) and the C-7 diastereoisomeric trichoverrins (C-6"S) (140) and isotrichoverrins (C-6"R) is unclear and has still to be tested with specifically labelled compounds. The pattern of secondary metabolites which could be intermediates, verrucarol (138), verrol (139), the trichodermadienediols (136) and the trichoverrols (137), again suggests a metabolic grid rather than a unique pathway. 

The mechanism of p—carotene cleavage is still unproven, but probably involves oxidative 15,15 cleavage to retinal. The sequence involves the loss of a C2 unit, a reduction of the 11,11 double bond and a series of oxidations. The nature of the proposed metabolic grid, with the different steps in the two different mating types, explains why trisporic acid is only synthesised when the two thalli are in diffusion contact i.e. the intermediates (and/or enzymes) can then diffuse from one cell to the other to complete the metabolic pathway. 

Fig, 3. Proposed metabolic grid scheme for the collaborative biosynthesis of trisporic acid showing mating-type specific reactions. 

Investigations with enzyme preparations are of importance in the elucidation of the details of secondary metabolic pathways. Each step can be examined independently from the metabolic grid of the producer cell, i.e., without interference from other transformations of the administered precursor or the products formed. The reaction in question can be measured by following the transformation of the substrates as well as the synthesis of the products and the consumption of cosubstrates, e.g., NADH or NADPH. The sensitivity of the determination of enzyme activities can be improved by sophisticated methods using other enzymes or isotopes. 

The involvement of a metabolic grid in which inteiconversion of various 4 -hydroxycinnamyl derivatives participate. (See Scheme 44). 

Figure 1.9. Proposed general metabolic grid of the biosynthesis of diamino acids. A. decarboxylation B. cyclization C. methylation. Pathway A leads to symmetrically labeled compounds in pathways B and C the original asymmetry is retained.

Figure 1.18a. Proposed metabolic grid for the biosynthesis and interconversions of quinolizi-dine alkaloids and related products in Fabaceae (Papilionaceae). For definition of symbols, see Table 1.2. Construction of the metabolic grid of lupine alkaloids The data on the various conversions of the lupine alkaloids were used to construct short metabolic pathways. Data concerning the distribution of lupine alkaloids in Leguminosae were drawn from Boit (1961) Cranmer and Turner (1967) Mears and Mabry (1971) Aslanov et al. (1972) Wicky and Steinegger (1965) Faugeras and Paris (1968) Bratek and Wiewiorowski (1959) Balcar-...

Table 1.2. Metabolic Grid Symbols and Extent of Occurrence of Fabaceae (Papilionaceae) Alkaloids and Precursors ... 

Although the results presented so far indicate an interdependency between the PN cycle and ricinine biosynthesis, the details concerning the order of intermediates in ricinine biosynthesis have not been elucidated. The conflicting evidence (Waller et aL, 1965 Hiles and Byerrum, 1969) in which the PN cycle intermediate is the immediate precursor of ricinine may best be explained by a complicated relationship between the cycle and ricinine biosynthesis. One possible relationship is the metabolic grid concept, which is defined as a series of pm allel reactions in which analogous transformations occur, but at different rates thus a compound may be converted to a product by several different parallel pathways (Bu Lock, 1965). The proposed metabolic grid, as shown in the structure. Figure 6.37, in which several of the PN cycle intermediates enter into the ricinine biosynthesis pathway, explains the similarity of radioisotopic incorporation results when each of the PN cycle intermediates ([ C]-labeled) were fed (Waller et al., 1965). It is presumed that these reactions are catalyzed by their respective enzymes. The report that a tenfold excess of NAD blocks... 

Figure 6.37. A metabolic grid proposed for the biosynthesis and control of metabolism of ricinine. A1—quinolinic acid A2—nicotinic acid mononucleotide A3—nicotinic acid adenine dinucleotide A4—nicotinamide adenine dinucleotide A5—nicotinamide A6—nicotinic acid A7—nicotinamide mononucleotide B1— AT-demethjiiicinine B2— ricinine Cl— N-methylnicotinic acid and C2— AT-methylnicotinamide. pyridine nucleotide cycle and postulated reaction sequence (Nowacki and Waller 1975a). Courtesy of Pergamon Press, Ltd., copyright 1975.

Catechol-O-methyltransferase from rat liver requires S-adeno-sylmethionine as a methyl donor and can methylate catechol but not monohydroxy derivatives of phenylethylamine. In vivo, O-methylation occurs exclusively in the meta position to the carbon side chain, but with purified preparations of the enzyme in vitro methylation can lead to both meta and para methylation. The ratio of products is susceptible. to both the polarity of the substrate and the pH of the medium . In man 3-methoxy-4-hydroxy-mandelic acid (18) comprises about 40 per cent of the total urinary metabolites produced from the catecholamines whilst in other pecies 3-methoxy-4-hydroxyphenylglycol (19), isolated as a sulphate ester, is the predominant breakdown product . A typical metabolic grid which indicates the possible types of pathway leading from noradrenalin (17) to both of these metabolites is shown in Figure 4.4 analogous metabolic schemes may be drawn up for both adrenalin and dopamine. 

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