Metabolic channeling

While PAL itself is recovered from the soluble fractions of cellular lysates via ultracentrifugation purifications, strong experimental evidence suggests it exists as part of a multienzyme complex associated with the endoplasmic reticulum (ER), forming a metabolic channel tunneling substrates directly from one enzymatic reactive site to another (Winkel 2004). The enzyme physically anchored to the ER is cinnamate... 

Winkel BSJ. 2004. Metabolic channeling in plants. Annu Rev Plant Biol 55 85-107. 

METABOLIC CHANNELING CHAOTROPIC AGENTS HOFMEISTER SERIES KOSMOTROPES... 

A role for enzyme complexes in the metabolic channeling of substrate has been proposed, so that competition between alternate enzyme pathways can be managed and the production of a specific product from a range of possibilities is favored. Furthermore, isoforms of the different enzymes may assemble in particular complexes dedicated to specific classes of flavonoid. 

Rasmussen, S. and Dixon, R.A., Transgene-mediated and elicitor-induced perturbation of metabolic channeling at the entry point into the phenylpropanoid pathway. Plant Cell, 11, 1537, 1999. 

Jorgensen K, Rasmussen AV, Morant M, Nielsen AH, Bjarnholt N, Zagrobelny M, Bak S, Moller BL. (2005). Metabolon formation and the metabolic channelling in the biosynthesis of NPs. Current Opinion in Plant Science, 8,280-291. 

Phenylpropanoid Pathway, Subcellular Localization, and Metabolic Channeling 509... 

Achnine L, Blancaflor EB, Rasmussen S, Dixon RA. 2004. Colocalization of L-phenylalanine ammonia-lyase and cinnamate 4-hydroxylase for metabolic channeling in phenylpropanoid biosynthesis. Plant Cell 16 3098-3109. 

Note that fatty acid synthesis provides an extreme example of the phenomenon of metabolic channeling neither free fatty acids with more than four carbons nor their CoA derivatives can directly participate in the synthesis of palmitate. Instead they must be broken down to acetyl-CoA and reincorporated into the fatty acid. 

Eukaryotic organisms contain a multifunctional enzyme with carbamoylphosphate synthetase, aspartate transcarbamoylase, and dihydroorotase activities. Two mechanisms control this enzyme. First, control at the level of enzyme synthesis exists the transcription of the gene for the enzyme is reduced if an excess of pyrimidines is present. Secondly, control exists at the level of feedback inhibition by pyrimidine nucleotides. This enzyme is also an example of the phenomenon of metabolic channeling aspartate, ammonia, and carbon dioxide enter the enzyme and come out as orotic acid. 

Keywords. Metabolic flux analysis, Flux estimation, Compartmentation, Metabolic channeling,... 

Fig. 6. Two pathways leading from propionate to pyruvate. The methyl citrate pathway gives retention of the carbon positions. The methylmalonyl-CoA pathway proceeds via the symmetrical intermediates succinate and fumarate, and the carbon atoms in pyruvate therefore reflect the scrambling that may take place as a consequence of the symmetry of these intermediates. If metabolic channeling takes place, only one of the two possible labeling patterns of malate is formed...

The discussion of metabolic channeling in the examples above has focused on new pathways as alternative explanations for the results. However, the complexity of metabolic networks offers a variety of different features that influence the labeling patterns. Theories based on the existence of alternative pathways do not give a satisfactory explanation for the reports of time-dependent labeling asymmetry, attributed to metabolic channeling, which has been observed in both yeast and mammalian tissue [40,43]. In these cases one has to consider other structures in the metabolic network, e.g., compartmentation of... 

Fig. 9. Mannitol cycle. The net result of one turn of the cycle is the conversion of NADH and NADP+ into NAD+ and NADPH, respectively, at the expense of ATP. Since mannitol is a symmetrical molecule, the cycle causes scrambling of the carbon atoms of fructose 6-phosphate unless metabolic channeling takes place [52]...

Due to the complexity of the metabolism, investigation of metabolic networks necessitates powerful analytical methods, both experimentally and mathematically. Figure 11 illustrates some of the metabolic aspects, e.g., metabolic channeling and reversible reactions, that complicate the analysis of metabolic networks. 

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