Organization of pathways

Once an enzyme-catalysed reaction has occurred the product is released and its engagement with the next enzyme in the sequence is a somewhat random event. Only rarely is the product from one reaction passed directly onto the next enzyme in the sequence. In such cases, enzymes which catalyse consecutive reactions, are physically associated or aggregated with each other to form what is called a multi enzyme complex (MEC). An example of this arrangement is evident in the biosynthesis of saturated fatty acids (described in Section 6.30). Another example of an organized arrangement is one in which the individual enzyme proteins are bound to membrane, as for example with the ATP-generating mitochondrial electron transfer chain (ETC) mechanism. Intermediate substrates (or electrons in the case of the ETC) are passed directly from one immobilized protein to the next in sequence. 

Biochemical reactions are interesting but they are not magic . Individual chemical reactions that comprise a metabolic pathway obey, obviously, the rules of organic chemistry. All too often students make fundamental errors such as showing carbon with a valency of 3 or 5, or failing properly to balance an equation when writing reactions. Furthermore, overall chemical conversions occur in relatively small steps, that is there are usually only small structural changes or differences between consecutive compounds in a pathway. 

This exercise is conceptually similar to biochemical conversions. One of the skills of the experimental biochemist is to identify metabolic intermediates and then to 

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As research reveals the ultrastructural organization of the cell in ever greater detail, more and more of the so-called soluble enzyme systems are found to be physically united into functional complexes. Thus, in many (perhaps all) metabolic pathways, the consecutively acting enzymes are associated into stable multienzyme complexes that are sometimes referred to as metabolons, a word meaning units of metabolism. ... 

First, let us briefly examine the route of side chain degradation in micro-organisms. The pathway is illustrated in Figure 92. 

Moore, P.J., Swords (1991) Spatial organization of the assembly pathways of glycoproteins and complex polysaccharides in the golgi apparatus of plants. J.Cell Biol. 112 589-602. 

Cain RB, RF Bilton, JA Darrah (1968) The metabolism of aromatic acids by micro-organisms. Metabolic pathways in the fungi. Biochem J 108 797-828. 

Martinez-Marcos A., Lanuza E. and Halpem M. (1999). Organization of the ophidian amygdala chemosensory pathways to the hypothalamus. J Comp Neurol 412, 51-68. 

The fact that molecular components are organized in pathways, networks and complexes used for different tasks in the organism explains, at least partly, the existence of pleiotropy as shown in particular by gene inactivation studies. 

This pleiotropic action of developmental genes is easily explained by the fact that the proteins encoded by these genes are components of pathways and networks, which have been repeatedly used during evolution for the construction of organisms. 

There is but one major set of reductive routes from non-metals to small organic molecules in the metabolome including molecules for energy distribution. They gave rise to the biopolymers also by one basic set of pathways. 

Some such starts were undoubtedly abiotic but the main paths only became firmly established in reproductive organisms. These pathways are set out in detail in wall charts and in all biochemical textbooks, but they usually omit the inorganic elements essential to all pathways. The primitive pathways to nucleic acids involved the synthesis of phosphorylated sugars and we envisage the bases as starting from HCN and NH3... 

Figure 7.2 Organization of specific signaling modules. (A) The arrangement of upstream and downstream kinases in a typical MAP kinase module is shown, the named examples being from the classical MAP kinase (ERK) pathway. (B) The known composition of mTORCl and mTORC2 is shown.

This pathway sets the direction for the remainder of this chapter but has the same basic strategy for the understanding of meteorite chemistry, comet chemistry, planetary atmospheric chemistry, prebiotic chemistry and ultimately the chemistry of an organism. This pathway is the molecule-up view of the Universe. 

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

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