Coenzymes primitive 203

It is here that we hit a central feature of every organism as well as the most primitive. There has to be spatial structure, there has to be flow, and there has to be communication to co-ordinate the activities of the cell. The communication has to link the metabolic paths and consists in the primitive cell of feedback controls by small molecules (mobile coenzymes and substrates) and ions, where up to 20 elements are involved. By seeing... 

The above description provides a possible starting background for the description of the beginning of cellular chemotypes, prokaryotes, but even this is less complicated than the only cells for which we have evidence since they have at least two additional groups of more sophisticated chemicals - coenzymes (see Tables 5.3 and 5.4) and certain metal cofactors, which we presume were additions to the most primitive cells. After we have described them, we shall return to the problem of cellular (cytoplasmic) organisation. Note that coenzyme novelty is not in basic pathways but in control of rates and in energy management. 

Subsequent to the original quest for vitamin B12 (1), driven by medicinal purposes mainly, further investigations on the natural corrinoids laid bare the central roles of the Bi2-coenzymes in the metabolism of microorganisms, in particular. These primitive organisms uniquely possess the capacity to build up the complex B12 structure in nature, in which they may vary the constitution of the nucleohde ftmchon in a species-specihc way (Figure 2). The cobalt-corrins, in turn, have been proposed to be structural and functional renmants of early (primihve) forms of life, where presumably, central metabolic processes could rely considerably on organometalhc chemistry at cobalt and nickel centers. ... 

And so the process would have continued. Unstable coacervates would have broken down and their organic material have become available once more for incorporation into stable ones. Stable coacervates would have grown and divided. Within them, more and more complex polymers would have been formed. Metal ions acting as catalysts for favoured reactions, and coenzymes such as nucleotides, would have become more active as they became bound to the peptide polymers which were the forerunners of proteins, thus forming proto-enzymes. Over the course of many hundreds of millions of years, the oceans would have become peopled with these stable, reproducing, primitive, semi-living droplets. At some... 

The reaction is basically the citric acid cycle run in reverse. Where the Krebs cycle takes complex carbon molecules in the form of sugars and oxidizes them to C02 and water, the reverse cycle takes C02 and water to make carbon compounds. This process is used by some bacteria to synthesize carbon compounds, sometimes using hydrogen or sulfates as electron donors. The reaction is a possible candidate for prebiotic early Earth conditions and so it is of interest in the origin of life. On the early Earth, a primitive form of acetyl-CoA-like thioacetate played the role of the essential coenzyme. It has been found that some of the steps can be catalyzed by minerals. Thus, the FeS world proposes that the reverse citric acid cycle operated nonenzymatically on the primitive Earth. The question is whether it is possible to retrace other ancient metabolic pathways. Combination of the recently found plugged... 

PLP itself, however, is presumably much older than this. There are general arguments suggesting that organic cofactors and coenzymes represent biochemical fossils from very primitive stages in the history of life. In particular, the fact that several cofactors show nucleotide-like features is often used to support the occurrence of an RNA world, that is, a very early phase of biotic evolution in which RNA molecules were capable of self-replication and of a rudimentary form of metabolism. Within this hypothetical world, cofactors and coenzymes would have helped expand the chemical repertoire of catalytic RNAs. "... 

The nickel-containing factor F 430 (134) provides an example of how nature exploits the reactivity of organometallic compounds, as is the case with vitamin B12. Factor F 430 (134) plays a key role as cofactor for the coenzyme M reductase of primitive methanogenic bacteria in the formation of methane from 2-(methylthio)-ethanesulfonate (86). The structural elucidation of factor F 430 (134) is based on a combination of classical spectroscopic methods, chemical degradation, and biosynthetic studies with C-labelled precursors 83a,b). These biosynthetic investigations will be addressed in section 8.2. Chemical degradation products obtained by ozonolysis of factor F 430 (134) allowed the determination of the absolute configuration by comparison with reference compounds derived from chlorophyll a (2) and vitamin B12 (4) 83a,b). 

Kritsky MS, Telegina TA Role of nucleotide-hke coenzymes in primitive evolution. In Origins genesis, evolution and diversity of life. Edited by Seckbach J. Springer 2004 215-230. 

Dithiol-disulphide redox roles in primitive systems would have favoured the development of dicysteinyl peptides, restraining two thiols in close proximity. Thioredoxin type molecules would have evolved from these small prototype dithiol peptides. Similar centres would also have developed as parts of more complex enzymes. The binding of a flavin coenzyme near a dithiol centre could eventually have produced the combined disulphide-flavoprotein centre with its special redox properties. 

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