Multi catalytic enzymes

The third type of modularity, the multi-catalytic enzymes using substrate channelling, are of particular interest for synthetic applications. Prominent members are the fatty acid synthases, the polyketide synthases and the non-ribosomal peptide synthases l42-44 . in these large proteins, a number of catalytic domains is combined with accessory domains and allows the catalysis of an entire pathway by a single polypeptide chain. Multi-catalytic enzymes frequently use a swinging arm , which is covalently attached to the intermediary product of one reaction step, and is subsequently able to present this molecule to the next catalytic domain for further... 

Product inhibition and substrate inhibition are effects also known in enzyme catalysis that can reduce catalytic efficiency. Generally, catalytic systems (natural or artificial) based on covalent interactions are more sensitive towards inhibitions than non-covalent systems utilizing weak interactions Garcia-Junceda, E. (2008) Multi-Step Enzyme Catalysis, Wiley-VCH Verlag GmbH, Weinheim, Germany. 

The most recently discovered group of proteases are the N-terminal threonine hydrolases of the multi-catalytic protease complex (MPC) of proteasomes. The enzymes are arranged in a regular array inside proteasomal compartments as shown in Box 7-A. The active site is a catalytic dyad formed from the amino group at the N terminus of the P subunits.345-3463... 

The proteolysis machinery involved in cell-cycle transitions comprises an ubiqui-tinating enzyme complex, 14-16 and a multicomponent protein complex with a multi-catalytic 26S proteasome. Proteasomes are abundant multisubunit particles. They comprise up to 1% of all cellular proteins. The proteolysis machinery is known in the... 

Several co-oxo fatty acids are transformed to the corresponding a,co -dicarboxylic acids, whereas -formylesters of fatty acids are decarboxylated to the co-hydroxy fatty acids and carbon dioxide1111. For several co-oxo fatty acids turnover frequencies (measured as O2 consumption) between 1.8 to 25 s 1 were found. Many P450 systems are multi-component enzymes with small protein cofactors such as putidaredoxin performing the electron mediation between NAD(P)H and the active site of the enzyme. Vilker and coworkers recently were able to show that NADPH can be omitted from the catalytic cycle by direct electrochemical reduction of putidar-... 

A given allosteric enzyme may have both positive and negative modulators. Allosteric enzymes are generally large multi-subunit enzymes. The allosteric site(s) may be on the same subunit(s) as the catalytic site(s) or on different subunits. The number of allosteric sites may be equal to the number of catalytic sites or they may be different. 

It is equally important to be able to enhance enzymic rates under some circumstances, and numerous activators or co-factors behave in this way. Often, especially in multi-subunit enzymes, these effects can be cooperative or allosteric, meaning that the binding of effectors or inhibitors on one subunit can affect the binding or catalytic properties on another subunit. The mathematics of such processes can get very complicated (and we will not do any of it here), but in such cases the simple Michaelis -Menten behaviour no longer applies. The advantage of such cooperative or allosteric effects is that they allow much tighter control of binding and catalytic processes. 

In Escherichia coli. Salmonella typhimurium and Aerobacter aerogenes two soluble multi-activity enzymes or enzyme complexes function in the utilisation of chorismate (14) for L-phenyl-alanine and L-tyrosine synthesis An enzyme or enzyme complex (P-protein) containing chorismate mutase and prephenate dehydratase activities has been isolated and partially purified from Escherichia coli. Salmonella typhimurium and Aerobacter aerogenes. The enzyme complex catalyses the transformation of chorismate (14) to phenylpyruvate (32) and both enzymic activities are retained in physical association after chromatography on DEAE cellulose. Kinetic analysis indicated that in isolated enzyme systems direct synthesis of phenylpyruvate (32) from chorismate (14) does not occur. Prephenate (31) once formed dissociates from the enzyme surface and accumulates in the reaction medium. After a lag period it is converted to phenylpyruvate (32). Schmit, Artz and Zalkin also obtained evidence to show that functionally distinct sites (catalytic and regulatory) exist on the P-protein from Salmonella typhimurium for chorismate mutase and prephenate dehydratase activities. The P-protein was obtained from Escherichia coli K-12 by Davidson, Blackburn and Dopheide who showed that it existed in solution mainly as a dimer of similar (and probably identical) sub-units of... 

Catalytic reduction of oxygen directly to water, while not as yet possible with traditional catalyst technology at neutral pH, is achieved with some biocatalysts, particularly by enzymes with multi-copper active sites such as the laccases, ceruloplasmins, ascorbate oxidase and bilirubin oxidases. The first report on the use of a biocatalyst... 

EIA systems take advantage of the extreme specificity and affinity with which antibodies bind antigens which stimulated their initial production, coupled to the catalytic efficiency of enzymes, which facilitates signal amplification as well as straightforward detection and quantification. In most such systems, the antibody is immobilized on the internal walls of the wells in a multi-well microtitre plate, which therefore serves as collection of reaction mini-test tubes. 

In the present paper we describe the catalytic mechanisms of synthetic polymer-Cu complexes a catalytic interaction between the metal ions which attached to a polymer chain at high concentration and an environmental effect of polymer surrounding Cu ions. In the latter half, the catalytic behavior is compared with the specific one of tyrosinase enzyme in the melanin-formation reaction which is a multi-step reaction. To the following polymers Cu ions are combined. 

The use of this enzyme in multi-step synthesis is relatively recent. Clapes et al. have reported the first example of FSA-mediated synthesis of iminocyclitols [53]. The synthetic strategy is similar to the one previously described for DHAP-dependent aldolases without the need for the dephosphorylation step. AldoUc reaction of DHA with N-Cbz-3-aminopropanal catalyzed by FSA followed by selective catalytic reductive aminahon furnishes the naturally occurring imino-sugar D-fagomine (Scheme 4.22). 

The cytochrome P450 system is the principal enzyme system for the metabolism of lipophilic xenobiotics. It is a heme-containing, membrane-bound, multi-enzyme system which is present in many tissues in vivo but is present at the highest level in liver. A coenzyme, cytochrome P450 NADPH oxidoreductase (OR), is essential for P450 catalytic function and cytochrome bs may stimulate catalytic activities of some enzymes. In human liver, it is estimated that there are 15-20 different xenobiotic-metabolizing cytochrome P450 forms. A standard nomenclature, based on relatedness of the amino acid sequences, has been developed (Nelson et al., 1993). The most recent... 

Definition of allosteric enzymes and their function Allosteric enzymes are multi-subunit proteins that are regulated by molecules called effectors. The effectors bind noncovalently at a site other than the active site, and can alter the affinity of the enzyme for its substrate, modify the maximal catalytic activity of the enzyme, or both. Allosteric enzymes frequently catalyze the committed step early in a pathway. 

Electron tunneling may also be of significance for redox catalysis, including enzyme catalysis. In particular it may turn out to be a tool for carrying out catalytic reactions via multi-electron paths. For instance, according to the data of ref. 11, the two-electron reduction of molecular oxygen to hyd-... 

We apply the concept of catalytic commitment, as proposed by Northrop, O Leary, and Cleland for multistep enzyme-catalyzed processes, to nonenzy-mic decarboxylation for comparison.52 The interpretation of CKIEs for decarboxylation reactions is dependent upon whether the process is viewed as a single-step or multi-step process. In a single-step mechanism, carbon-carbon bond-breaking is not affected by any other rate-limiting process. In this case, the CKIE for a particular compound will be constant under a standard set of conditions. Substantial changes in bond order must occur in the... 

---