Biological systems activity cofactor

Immobilization. Enzymes, as individual water-soluble molecules, are generally efficient catalysts. In biological systems they are predorninandy intracellular or associated with cell membranes, ie, in a type of immobilized state. This enables them to perform their activity in a specific environment, be stored and protected in stable form, take part in multi-enzyme reactions, acquire cofactors, etc. Unfortunately, this optimization of enzyme use and performance in nature may not be directiy transferable to the laboratory. 

Distinct coenzymes are required in biological systems because both catabolic and anabolic pathways may exist within a single compartment of a cell. The nicotinamide coenzymes catalyze direct hydride transfer (from NAD(P)H or to NAD(P)+) to or from a substrate or other cofactors active in oxidation-reduction pathways, thus acting as two-electron carriers. Chemical models have provided... 

Ribonucleotide reductase is notable in that its reaction mechanism provides the best-characterized example of the involvement of free radicals in biochemical transformations, once thought to be rare in biological systems. The enzyme in E. coli and most eukaryotes is a dimer, with subunits designated R1 and R2 (Fig. 22-40). The R1 subunit contains two lands of regulatory sites, as described below. The two active sites of the enzyme are formed at the interface between the R1 and R2 subunits. At each active site, R1 contributes two sulfhydryl groups required for activity and R2 contributes a stable tyrosyl radical. The R2 subunit also has a binuclear iron (Fe3+) cofactor that helps generate and stabilize the tyrosyl radicals (Fig. 22-40). The tyrosyl radical is too far from the active site to interact directly with the site, but it generates another radical at the active site that functions in catalysis. 

IRadical cofactors in biological systems have become a subject of increasing interest in recent years (1-3). Tyrosine-based radicals, in particular, have now been identified in several enzymes (4). The tyrosine residue functions as a redox-active cofactor by interconverting between the oxidized phenoxyl radical and the normal phenol or phenolate states. More commonly known redox-active cofactors include transition metal ions, and a few enzymes use both tyrosine residues and metals as partners in effecting redox chemistry. 

The copper-containing enzymes can be classified as mononuclear, binuclear, or multicopper proteins (9). Unlike iron, copper caimot readily access high oxidation states and the formation of Cu in biological systems remains controversial. Generally, Cu centers undergo one electron oxidations to activate dioxygen. Thus, the Cu-containing enzymes tend to employ multiple copper atoms or an additional cofactor for the final two or four-electron oxidation of their substrates. 

The catalysts in biological systems are enzymes, and nearly all enzymes are proteins. Enzymes are highly specific and have great catalytic power. They can enhance reaction rates by factors of 10 or more. Many enzymes require cofactors for activity. Such cofactors can be metal ions or small, vitamin-derived organic molecules called coenzymes. 

There has been far less research performed on the role of short-range electrostatic interactions such as cation- [39] and other polar- [40] effects on the reduction potential of organic cofactors. The effects of these interactions on biological systems are hard to assess mutation of charged residues near the active site perturbs multiple aspects of the catalytic process [41], whereas dipolar interactions are often subtle, and are extremely distance dependent [42]. One model study has been performed on the donor atom- interaction of electron-rich functionality with flavins [43]. These studies used a model system (Figure 11) to explore the role of this interaction... 

Biological cell membranes are multi-component systems consisting of a fluid bilayer lipid membrane (BLM) and integrated membrane proteins. The main structural features of the BLMs are determined by a wide variety of amphiphilic lipids whose polar head groups are exposed to water while hydrocarbon tails form the nonpolar interior. The BLMs act as the medium for biochemical vectorial membrane processes such as photosynthesis, respiration and active ion transport. However, they do not participate in the corresponding chemical reactions which occur in membrane-dissolved proteins and often need redox-active cofactors. BLMs were therefore mostly investigated by physical chemists who studied their thermodynamics and kinetic behaviour . ... 

The range of functionality provided by the 20 amino acids found in proteins consists of weak acids and bases, nucleophiles, hydrogen bond donors and acceptors, and the redox active thiol/disulfide. This limited range of chemistry is inadequate for the catalysis of many reactions found to occur in biological systems. Therefore, a variety of small organic molecules, called cofactors, coenzymes, or vitamins, have evolved to broaden the limited range of chemistry that can be catalyzed by simple proteins. 

Artificial enzymes may be divided into two categories semisynthetic artificial enzymes and synthetic artificial enzymes. Semisynthetic artificial enzymes are partly prepared by biological systems. Catalytic antibodies are typical examples of semisynthetic artificial enzymes. Semisynthetic artificial enzymes are also prepared by modification of a known protein or enzyme at a defined site with a cofactor or new functional group. Synthetic artificial enzymes are prepared totally by synthetic methods. Synthetic artificial enzymes may be either relatively small molecules with well-characterized structures or macromolecules. The term syn-zymes has been coined to designate synthetic polymers with enzyme-like activities. In addition, synthetic artificial enzymes are also obtained with molecular clusters such as micelles and bilayer membranes formed by amphiphiles. 

Electron-transfer (ET) reactions play a central role in all biological systems ranging from energy conversion processes (e.g., photosynthesis and respiration) to the wide diversity of chemical transformations catalyzed by different enzymes (1). In the former, cascades of electron transport take place in the cells where multicentered macromolecules are found, often residing in membranes. The active centers of these proteins often contain transition metal ions [e.g., iron, molybdenum, manganese, and copper ions] or cofactors as nicotinamide adenine dinucleotide (NAD) and flavins. The question of evolutionary selection of specific structural elements in proteins performing ET processes is still a topic of considerable interest and discussion. Moreover, one key question is whether such stmctural elements are simply of physical nature (e.g., separation distance between redox partners) or of chemical nature (i.e., providing ET pathways that may enhance or reduce reaction rates). 

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