Multistep pathways

Fig. 17. The receptor-internalization process via a coated pit in which receptors are internalized and processed in a multistep pathway before being recycled...

Biotin is produced by a multistep pathway in a variety of fungi, bacteria, and plants (50—56). The estabUshed pathway (50,56) in E. coli is shown in Figure 6. However, Htde is known about the initial steps that lead to pimelyl-Co A or of the mechanism of the transformation of desthiobiotin to biotin. Pimelic acid is beheved to be the natural precursor of biotin for some microorganisms (51). 

The amino acid cysteine, C3H7NO2S, is biosynthesized from a substance called cystathionine by a multistep pathway. 

The whole process of chlorophyll disappearance in vascular plants is a complex multistep pathway, much as chlorophyll biosynthesis is, but for didactic reasons it can be abbreviated into two main stages. The first group of reactions produces greenish derivatives while the more advanced steps produce colorless compounds by an oxidative ring opening, analog to the oxygenolytic rupmre of the porphynoid macrocycle of haem. It is a very rapid process and despite considerable efforts, the detection of intermediates is difficult. ... 

Schwarz, H. Some Newer Aspects of Mass Spectrometric Ortho Effects. 73, 231-263 (1978). Schwarz, H. Radical Eliminations From Gaseous Cation Radicals Via Multistep Pathways — The Concept of Hidden Hydrogen Rearrangements, 97, 1-31 (1981). 

The main feature of bifunctional catalysts is not only the appearance of novel catalytic functions but also its mode of operation various functions may (and sometimes should) participate alternately in the transformation of one single molecule. Consequently, various multistep pathways may lead to the same end product. In this situation it can be extremely difficult to distinguish between the role of individual catalytic functions. Three experimental approaches have been offered ... 

It is obvious that the biosynthesis of such a complex structure involves many proteins and steps. In fact, the anchor is synthesized in the ER, requiring a membrane-bound multistep pathway in which more than 20 gene products, mainly polytopic membrane proteins, take part." " The first two steps of the biosynthesis occur on the cytoplasmic site of the ER, and after flipping to the lumen of the ER the biosynthesis is completed. The GPI... 

Structure and Function of Peptidyl Carrier Protein Domains Structure and Function of Adenylation Domains Structure and Function of Condensation Domains Structure and Function of Thioesterase Domains Multidomain NRPS Structural Information PCP-C didomain structure PCP-TE didomain structure Structure of a C-A-PCP-TE termination module Pathways to Nonproteinogenic Amino Acids Incorporated into NRP Natural Nonproteinogenic Amino Acids Present as Cellular Metabolites Modification of Proteinogenic Amino Acids Nonproteinogenic Amino Acids Derived from Multistep Pathways Tailoring Enzymology in NRP Natural Products Chemical Approaches Toward Mechanistic Probes and Inhibitors of NRPS... 

Nonproteinogenic Amino Acids Derived from Multistep Pathways... 

Note that in the case of fluorescence, where the energies involved indicates that spontaneous emission in the form of a simple single transition should dominate. Nevertheless the typical pathways back to the ground state appear to involve multiple transitions where the excited state interchanges low energy photons with the environment. We thus have a case where the dynamics of the environment may facihtate a more efficient but complex multistep pathway back the ground state than spontaneous emission provides. 

In summary, we see that the interpretation of the Bronsted parameter a is far from straightforward. In addition to the intrinsic factors discussed here, there may also be extraneous factors which affect the magnitude of the Bronsted parameter. These include solvation factors (Jencks et al., 1982 Hupe and Jencks, 1977 Hupe and Wu, 1977), and multistep pathways (Murdoch, 1972). So while in certain cases the Bronsted parameter does... 

FIGURE 22-15 Biosynthesis of six essential amino acids from oxalo-acetate and pyruvate in bacteria methionine, threonine, lysine, isoleucine, valine, and leucine. Here, and in other multistep pathways, the enzymes are listed in the key. Note that L,L-a,e-diaminopimelate, the product of step (HI), is symmetric. The carbons derived from pyruvate (and the amino group derived from glutamate) are not traced beyond this point, because subsequent reactions may place them at either end of the lysine molecule. 

Dual-function catalysts possessing both metallic and acidic sites bring about more complex transformations. Carbocationic cyclization and isomerization as well as reactions characteristic of metals occurring in parallel or in subsequent steps offer new reaction pathways. Alternative reactions may result in the formation of the same products in various multistep pathways. Mechanical mixtures of acidic supports (silica-alumina) and platinum gave results similar to those of platinum supported on acidic alumina.214,215 This indicates that proximity of the active sites is not a requirement for bifunctional catalysis, that is, that the two different functions seem to operate independently. 

A multistep pathway analogous to the mechanism of alkene hydrogenation has been shown to be operative in the rhodium-catalyzed hydroboration of alkenes.363 Deuterium labeling studies furnished evidence that the reversibility of the elementary steps is strongly substrate-dependent. The key step is hydride rather than boron migration to the rhodium-bound alkene. 

Most biochemical reactions are integrated into multistep pathways using several enzymes. For example, the breakdown of glucose into C02 and H20 involves a series of reactions that begins in the cytosol and continues to completion in the mitochondrion. A complex series of reactions like this is referred to as a biochemical pathway (fig. 1.19). 

Biochemical reactions are frequently organized into multistep pathways. 

Enzymes that are susceptible to direct regulation occupy key positions in metabolic pathways. In a multistep pathway the first enzyme in the pathway is usually regulated, and the others are not (fig. 11,8a). In the case of CTP synthesis (see chapter 9), we saw that the enzyme aspartate car-... 

Different procedures are used for analysis of simple and complex pathways. Analysis of single-step pathways often begins with the isolation and characterization of the enzyme involved. During enzyme isolation each purification step is monitored by a specific assay that measures the conversion of substrate to product. Multistep pathway analysis ideally begins with complementation analysis, a genetic technique that entails the isolation of mutants with genetic blocks in each step of the pathways. Once the numbers of enzymes and intermediates are established, each enzyme can be isolated with the help of a specific assay. 

Synthesis and degradation of fatty acids. Both synthesis and degradation of fatty acids occur by multistep pathways involving totally different enzymes located in different parts of the cell. Both pathways are similar in that two carbon atoms are either added (in synthesis) or deleted (in degradation) in each round of a repetitious, cyclical process. 

The multistep pathway 81 explains some observed features, including the evaluation of the electronic effect of substituents81,97 using the Hammett (p/cr) equation which is a non-linear correlation, but it may also be explained by a single reaction with two or... 

The CH3SOH product of reaction (4c) is expected to react with O2 to produce MSA. Further studies are needed to establish whether DMSO is formed directly via reaction (4b) or via a multistep pathway involving production and subsequent oxidation of DMSO. If DMSO2 is, indeed, formed via reaction (4b), then the source of the oxygen enhancement observed in our experiments needs to be identified. 

Total synthesis in vitro is a major step forward from the conventional use of enzymes in organic synthesis. In traditional synthesis, an enzyme catalyst is employed to carry out only a single transformation in a multistep pathway. In this new technology, however, all of the processes are biological, including the key carbon-carbon bond-forming reactions. 

The 10 amino acids essential in the human diet (Arg, His, He, Leu, Lys, Met, Phe, Thr, Trp, Val) are synthesized by non-human organisms by multistep pathways starting from simple metabolic precursors. Amino acid biosynthesis is controlled by feedback inhibition and suppression of synthesis of biosynthetic enzymes. The ability of an amino acid analogue to block biosynthesis of the parent amino acid often contributes to the toxicity of the analogue. Mutants resistant to the toxic effects of the analogue can be valuable tools for studying various aspects of cellular mechanism (examples to be given below). 

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