Enzyme clusters

It is obvious that the answer is the principle of spatial correlation, that is, the compartmentalization of a metabolism via the formation of oligomeric enzymes, enzyme clusters, and physical association of enzymes in metabolic sequences anchored on membranes. 

Three types of enzyme clustering are found (fig. 11.3). In the simplest situation, all of the catalytic activities for a particular pathway are found in proteins that exist as independent soluble proteins in the same cellular compartment. In such cases the intermediates must get from one enzyme to the next in the sequence by free diffusion through the cytosol or by transfer after contact between two sequentially related enzymes—one carrying the reactive intermediate and the other ready to receive it. Such is the situation for the enzymes involved in the breakdown of glucose to pyruvate. 

The overall relative orientation of the secondary structures of an enzyme determines its three-dimensional shape, or tertiary structure. Some enzymes require multiple copies of the same enzyme to function. The individual enzymes cluster into groups of two or more (called dimers, trimers, etc.) and are held together by intermolecular forces. The relative positioning of the separate enzymes in the cluster determines the overall structure, or quaternary structure, of the supramolecular complex. While all enzymes have tertiary structure, only clusters of multiple enzyme subunits have quaternary structure. The overall folded conformation of a protein in its active, catalytic form is called the active or native conformation. 

Figure 1. The sequential emergence of enzyme clusters in developing liver.

We will learn to produce mimics of enzyme clusters, imitating natural clusters such as gene transcription assemblies. We will learn to produce artificial enzymes that show induced fit, and allosteric control by analogs of hormones. Then we will move to mimics of cells themselves, with their components of many enzymes, to achieve chemical processes more complex than those done by a single enzyme. The biochemistry of life is impressive, but the role of chemistry is not just to admire it. As humans were impelled to invent ways to fly after observing birds, we will learn to create a new area of chemistry - biomimetic reaction chemistry - adding both to our understanding and to our practical abilities. 

One approach is set out in Fig. 29 (226). Subsite-derivatized cluster 56, carrying a pyridine-4-thiolate ligand, reacts with the Fe(II) complexes Fe(acen) and Fe(OEP) to afford in equilibrium mixtures the bridged assemblies 57 and 58, respectively, having an oxidation state corresponding to SiR " of the enzyme. Cluster 56 was isolated, and Reaction 19 was conducted in acetonitrile and Reaction 20 in thf. Products 57 and 58 have been identified by their H NMR spectra, which show differences compared to the spectra of the uncombined cluster and complexes that are consistent... 

Arts. Yes. The vertebrate cell consists of a number of compartments and subcellular structures in which enzymes and enzyme clusters or complexes function. The compartments are enclosed in membranes, as is the cell itself. All membranes have complex functions including specific transport by specialized proteins and enzymatic processes central to metabolism. For example, if the inner mitochondrial membrane is disrupted, synthesis of ATP will cease. 

Although fundamentally similar in bacteria and eukaryotic cells, transcription and translation must differ in details because of the difference in structural organization and of the surrounding environment. The environment of bacterial cells may change suddenly and considerably, but that of mammalian cells is stable because of homeostatic control. Therefore, metabolic patterns are much more stable in mammalian than in bacterial cells, and ordinarily there is no need for the sudden appearance of enzyme clusters like those that appear in bacteria challenged by inducers. Thus, it may not be necessary to produce polycistronic messenger in mammalian cells. Moreover, the mammalian cell may find it advantageous to maintain stable templates. 

Enzyme applications cofactor recycling techniques, enzyme immobilization, enzyme solubilization, enzyme recycling, multi-enzyme clusters, mini- and micro-scale application tests, new enzyme analytical and separation techniques. 

Genetically modified enzymes were involved in the articles by DeAngelis (19), Wang et al (17), and Henderson (5). A genetically modifi protein was prepared by Patwardhan et al (14), Wang et al (17) devised multi-enzyme clusters (Superbeads) and cells containing multiple pathways (Superbugs). 

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