Proto-metabolism

Several processes involving the continuous feeding in activated reactants supplying chemical energy have been proposed to lead to the emergence of proto-metabolisms (otherwise called chemo-metabolisms), defined as a sequence of thermodynamically favorable chemical reactions (usually cyclic) through which more evolved species could have been produced, and that could have been the starting point from which life developed. 

Catalysts played an important role in the emergence of life on Earth nearly 4 billion years ago. Catalysis by mineral surfaces and small molecules enabled the emergence of a proto-metabolic network that, in turn, enabled the emergence of the RNA world. The first macromolecular catalysts may have been ribozymes, an idea first proposed by Carl Woese that gained credence with the discovery of catalytic RNAs by Cech and Altman. Subsequently, ribozymes generated by in vitro evolution methods have been shown to catalyze a wide range of reactions involved in metabolism, including amino acid activation formation of coenzyme A (CoA), nicotinamide adenine dinucleotide (NAD), and flavin adenine dinucleotide (FAD)... 

The RNA world model is not without its difficulties. Foremost among these problems is the exceptional challenge in the prebiotic synthesis of RNA (39-40). Many of the presumed proto-metabolic molecules are easily synthesized in experiments that mimic prebiotic environments. RNA nucleotides, by contrast, have never been synthesized from scratch. Furthermore, even if a prebiotic synthetic pathway to nucleotides could be found, a plausible mechanism to link those nucleotides into an RNA strand has not been demonstrated. It is not obvious how useful catalytic RNA sequences would have formed spontaneously in any prebiotic environment. Perhaps, some scientists speculate, a simpler nucleic acid preceded RNA (41-42). 

In this chapter we use the term proto-metabolism for specifying networks of reactions capable of performing chemical transformations and inducing self-organisation features in a chemical system. From this definition, there is fundamentally no difference between metabolic and proto-metabolic pathways except that enzyme catalysis makes metabolism much more efficient in achieving its function and generates multiple possibilities of feedback control almost without any limitations. 

This relationship does not depend on another variable than these three parameters and will be used as a tool to detect conditions in which self-organisation based on proto-metabolic fluxes of energy can take place. Selecting a value of 1 for the transmission coefficient k (meaning that there is no possibility of reverting to the reactants after the system has crossed the transition state), the value of the free energy of activation can then be deduced as a function of the half-life of a first-order (or pseudo-first-order) reaction at different values of temperature (Fig. 8.6). 

Revealing that there is a quantitative relationship between the timescale of a proto-metabolism (this timescale may be related to the turnover frequency for a catalytic cycle [66]) and the height of the kinetic barriers that must be present for protecting the metabolites or carriers that are involved in exchanges with the... 

Use of the first oxidised products by proto-aerobic organisms - sulfate, ferric ions, and probably nitrogen oxides. Molybdenum became more available and was generally required for N and S metabolism (three to two billion years ago). 

The sequence of events from mutations or damage to proto-oncogenes and leads to tumour suppressor genes, loss of development of cancer, with its metabolic disturbances and cachexia. Finally these changes can lead to... 

What does your intuition say did macromolecular self-replication systems come first in the origin of life or should they be seen as the product of a mature cellular or proto-cellular metabolism ... 

Gabaldon T, Huynen MA (2003) Reconstruction of the proto-mitochondrial metabolism. Science 301 609... 

Marczak R, Gorrell TE, Muller M (1983) Hydrogenosomal ferredoxin of the anaerobic proto-zoon, Tritrichomonas foetus. J Biol Chem 258 12427-12433 Muller M (1973) Biochemical cytology of trichomonad flagellates. I. Subcellular localization of hydrolases, dehydrogenases, and catalase in Tritrichomonas foetus. J Cell Biol 57 453-474 Muller M (1976) Carbohydrate and energy metabolism of Tritrichomonas foetus. In H Van den Bossche (ed.), Biochemistry of parasites and host-parasite relationships. Elsevier/North Holland, Amsterdam, pp 3-14... 

Gabaldon T (2005) Origin and evolution of the mitochondrial proteome. Applications for protein function prediction in the eukaryotes. Thesis, Nijmegen Gabaldon T, Huynen MA (2003) Reconstruction of the proto-mitochondrial metabolism. Science 301 609-609... 

So when does the first evidence of improbable, information-containing, metabolic replication occur in the fossil record The Earth is 4,500 million years old, as judged by several corroborating radionuclide studies of the oldest rocks on the planet show. Meteoric bombardment of the proto-Earth continued heavily until 4,000 MY A, probably precluding life during this period. The majority of the oldest rocks on Earth are 3,500 million years old, and the earliest microfossils are from 3,000+ MYA, hence we only have a window of about 500 million years from the end of the meteoric bombardment to the first signs of microbial life. This means we are either very lucky, or life is a high-on certainty ... 

Fong, A.T., R.H. Dashwood, R. Cheng, C. Mathews, B. Ford, J.D. Hendricks and G.S. Bailey. Carcinogenicity, metabolism and Yd-ras proto-oncogene activation by 7,12-dimethylbenz[a]anthracene in rainbow trout embryos. Carcinogenesis 14 629-635, 1993. 

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