Biochemical pathways branch points

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 mevalonate pathway, both the main trunk and its various branch points, has been the subject of intense biochemical and chemical research activity. There are several reasons for this interest. First, the wide variety of biologically important metabolites, which play a role in many cellular functions, naturally leads to research in this area. The development of... 

Morishige T, Dubouzet E, Choi K-B, Yazaki K, Sato F. Molecular cloning of columbamine O- methyltransferase from cultured Coptis japonica cells. Eur. J. Biochem. 2002 269 5659-5667. Hirata K, Poeaknapo C, Schmidt J, Zenk MH. 1,2-Dehydroreti-culine synthase, the branch point enzyme opening the morphinan biosynthetic pathway. Phytochemistry 2004 65 1039-1046. De-Eknamktil W, Zenk MH. Purification and properties of 1,2-dehydroreticuUne reductase from Papaver somniferum seedlings. Phytochemistry 1992 31 813-821. 

The thousands of enzyme-catalyzed chemical reactions in living cells are organized into a series of biochemical (or metabolic) pathways. Each pathway consists of a sequence of catalytic steps. The product of the first reaction becomes the substrate of the next and so on. The number of reactions varies from one pathway to another. For example, animals form glutamine from a-ketoglutarate in a pathway that has two sequential steps, whereas the synthesis of tryptophan by Escherichia coli requires 13 steps. Frequently, biochemical pathways have branch points. For example, chorismate, a metabolic intermediate in tryptophan biosynthesis, is also a precursor of phenylalanine and tyrosine. 

Extensive studies support the hypothesis that these phenazine precursors are derived from the shikimic acid pathway, as outlined in Scheme 1, with chorismic acid (51) as the most probable branch point intermediate. Shikimic acid (50) is converted to chorismic acid (51) in known transformations that are part of the common aromatic amino acid biosynthetic pathway. The transformation from chorismic acid (51) to the phenazine precursors has been discussed and investigated through intensive biochemical studies so far, no intermediates have been identified and little is known about the genetic origin and details of the phenazine biosynthesis. ... 

Figure 1. Proposed metabolic branching points to various phenylpropanoid pathway derivatives based on existing chemotaxonomic / biochemical data. a. Phenylalanine ammonia-lyase, b. Tyrosine ammonia-lyase, c. Cinnamate-4-hydroxylase, d. Hydroxylase, e. 0-Methyltransferase, f. Cinnamoyl-CoA NADP oxidoreductase, g. Cinnamyl alcohol dehydrogenase.

---