Precursor-product relationships

Fig. 12-1. Precursor-product relationship of atmospheric chemical reactions.

The prochirality concept is not necessarily an expression of a precursor-product relationship because there exist stereoselective reactions at pro-chiral elements that do not generate elements of chirality. An illustration of this is the reversible enzymatic dehydration of citric to cu-aconitic acid. In this process two prochiral centers of citric acid disappear and we obtain an achiral line of stereoisomerism that physically coincides with a prochiral plane of prostereoisomerism. 

Precursor-product relationships were studied in peanut cell cultures grown in B-5 Medium (8) that contained 2.8 ppm ( ClPCNB and 100 ppm 2,4-D. The liquid shake cultures were harvested after 3 hr, 9 hr, 24 hr, 3 days, 7 days and 14 days. The cells were extracted with 80% methanol and the extracts were made aqueous and partitioned against methylene chloride. Water-soluble metabolites were purified by various chromatographic methods and Identified by mass spectrometry in a manner similar... 

Precursor-product relationships were also studied in peanut plants treated with C-labeled metabolites and harvested 1 to 21 days later (, 7). 

In contrast to this work on whole brain, Kemp and Stoolmiller138 used cultured mouse-neuroblastoma cells for their study of incorporation of [ lH]2-acetamido-2-deox> -D-mannose into the sialic acid moiety of gangliosides. They were able to demonstrate clearly the precursor-product relationship among CMS, GM2, and GM1. They found that cultured NB41A cells incorporated [3H]2-acetamido-2-deoxy-D-man-nose into the sialic acid moiety of GM3 in less than 10 minutes. Labeled GM2 was not detected in cells incubated for less than 30 minutes, and measurable activity did not appear in G I1 until alter 60 to 90 minutes. These results further supported the concept that the pathway of synthesis of ganglio-tvpe gangliosides proceeds by way of GM3 —> GM2 — GM1. 

Another way of looking at metabolism, which emphasizes the precursor-product relationship, is depicted in figure 11.5. Here metabolism is pictured as three concentric boxes. The inner box shows the central metabolic pathways and the interconversions of various small molecules. These substances serve as the starting materials for all other metabolism. Some of the compounds formed from these intermediates are shown in the middle concentric box. These... 

Cl Biochemical precursor-product relationships vary in complexity. Some pathways such as the conversion of phenylalanine to tyrosine involve only one en-... 

Some of the best understood polyvalent interactions are found in immune and host defense systems as well as ligand-receptor activation. An example is the use of a polyvalent immunogen based on a synthetic peptide to elicit immune responses. The subsequent production of site-specific antibodies can then be employed to confirm the identity of proteins derived from recombinant DNA, to explore biosynthetic pathways, to define precursor-product relationships (e.g., proenzyme and preproenzyme), and to determine protein structural domains.19 ... 

Hormone-treated pea seedlings generate two physically distinct cellulases (EC 3.2.1.4), with similar substrate specificities, Km values, and inhibitor sensitivities. They may be effectively separated by sequential extraction with buffer and salt and they appear to possess identical active sites but different apoprotein structures. The question arises of why this tissue should elaborate two hydrolases which catalyze the same reactions. The cellulase that forms first is synthesized by and accumulates in vesicles, where it would never encounter cellulose, while the other is concentrated on the inner wall microfibrils. It is suggested that only the latter cellulase functions to hydrolyze cellulose. A precursor/ product relationship between them could explain their distribution and developmental kinetics, but physical and chemical differences mitigate against this interpretation. 

The chirality of a precursor product relationship was determined by the use of doubly labeled lysine, in which one enantiomer was labeled only with tritium and the other with tritium and 14C (55). Comparison of the 3H/14C ratios of substrate and products demonstrated that decodine and decinine were derived from L-lysine, whereas pipecolic acid (186) was derived from D-lysine. Thus, pipecolic acid does not serve as a precursor of Lythraceae alkaloids (57). 

Werne J. P., Hollander D. J., Behrens A., Schaeffer P., Albrecht P., and Damste J. S. S. (2000) Timing of early diagenetic suUurization of organic matter a precursor-product relationship in holocene sediments of the anoxic Cariaco Basin, Venezuela. Geochim. Cosmochim. Acta 64(10), 1741-1751. 

This initial survey of naturally occurring cyclopropanoid metabolites raises several questions relating to the biochemistry including function and metabolism of the compounds and in particular the cyclopropyl group. In the bulk of this chapter we summarize what evidence is available on modes of biosynthesis and degradation of cyclopropyl substituents. While in several cases, e.g. in terpenoids and steroids of the cycloartenol (20) case, biogenetic tracer studies or stereochemical probes have been carried out and are quite revealing about precursor-product relationships, there are very few cases indeed where specific enzymatic catalysts have been identified, isolated, and characterized for action on specific cyclopropane substrates. 

Studies of the precursor-product relationship in various biogenetically related humulene-derived metabolites have led to a unified scheme (equation 5) in which intramolecular cyclization of trans,trans-farnesyl pyrophosphate (73) generates humulene (74) by the attack at C(ll) of the distal double bond and loss of a proton from C(9) reprotonation at C( 10) of the key intermediate initiates further cyclization to a cyclobutyl-containing protoilludyl cation (75). Subsequent bond migration accompanied by contraction of the cyclobutane ring to the cyclopropane as shown, would then yield illudins. In accordance with the postulated pathway of illudin formation, C(l), C(14) and one of the... 

Fig. 9 shows a positive ion ESI mass spectrum from this degradation product acquired on a quadrupole ion trap, followed by a series of CID-MS/MS spectra in which the most abundant ion in the previous spectrum was selected as a parent (or precursor) ion. For example, the spectrum second from the top in Fig. 9 is a CID spectrum of the precursor ion m/z 329, the [M + H] of II, the next spectrum down is a CID spectrum of the precursor ion m/z 270, and so on to MS . The utility of this mass spectral information, and its ability to establish precursor-product relationships, should be obvious. 

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