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New knowledge on the origin, function and fate of osteoclasts.

The most recent findings on the origin, life-span and fate of the osteoclast can be summarized as follows. Osteoclasts originate from progenitor, mononuclear, lymphoid cells which reach the bone surface through the bloodstream. Osteoclasts resorb bone by secreting lysosomal enzymes and procollagenase in the osteoclast-bone interspace. The organic components of the matrix (first interfibrillary substance, then collagen fibrils) are digested in the extracellular space. Dislodged crystals and residual organic constituents are then phagocytosed and collected in cytoplasmic vacuoles where they are completely solubilized. The ruffled border and the adjacent "clear" zone constitute the resorbing apparatus, whose development is roughly proportional to osteoclast activity. Osteoclast nuclei are continuously incorporated and shed, so that individual cells are continuously renewed. This makes the life-span of the osteoclast extremely difficult to determine. The life of each individual osteoclast might theoretically continue as long as the stimulus to resorption persists and sufficient bone matrix is available. Primary abnormalities of the osteoclasts can induce pathologic skeletal changes, as in the case of osteopetrosis and Paget's disease of bone. Conversely, skeletal abnormalities may damage osteoclasts, as in the case of lead intoxication. When this happens, osteoclasts are essentially characterized by an underdeveloped ruffled border, pyknotic nuclei, detachment from the bone matrix and, finally, shrinkage and fragmentation. It is not yet known whether these changes only occur in pathologic conditions, or whether they are the alterations which lead senescent osteoclasts to death even in normal bone.

Animals↗

On the origin of biological systems and the role of poly-nucleotides -- the initiation of evolution, the structural basis of the genetic code and the mechanism of protein biosynthesis.

There is much information on the nature and function of biological systems in the structures of the small molecules that affect them and in the biosynthetic and other reactions in which they are involved. Combining this with biochemical and polynucleotide sequence information allows us to derive explanations for a number of biological problems that earlier were unclear or even quite obscure. Thus polynucleotide systems give a good account of the origin of life, of the genetic code and of the function of the ribosomal mechanism of protein biosynthesis. It is apparent that polynucleotides play a more important role than has been fully appreciated.

Biological Evolution↗

Influence of ionic inorganic solutes on self-assembly and polymerization processes related to early forms of life: implications for a prebiotic aqueous medium.

A commonly accepted view is that life began in a marine environment, which would imply the presence of inorganic ions such as Na+, Cl-, Mg2+, Ca2+, and Fe2+. We have investigated two processes relevant to the origin of life--membrane self-assembly and RNA polymerization--and established that both are adversely affected by ionic solute concentrations much lower than those of contemporary oceans. In particular, monocarboxylic acid vesicles, which are plausible models of primitive membrane systems, are completely disrupted by low concentrations of divalent cations, such as magnesium and calcium, and by high sodium chloride concentrations as well. Similarly, a nonenzymatic, nontemplated polymerization of activated RNA monomers in ice/eutectic phases (in a solution of low initial ionic strength) yields oligomers with > 80% of the original monomers incorporated, but polymerization in initially higher ionic strength aqueous solutions is markedly inhibited. These observations suggest that cellular life may not have begun in a marine environment because the abundance of ionic inorganic solutes would have significantly inhibited the chemical and physical processes that lead to self-assembly of more complex molecular systems.

Calcium↗

Aqueous synthesis of peptide thioesters from amino acids and a thiol using 1,1'-carbonyldiimidazole.

A new method was developed for the synthesis of peptide thioesters from free amino acids and thiols in water. This one-pot simple method involves two steps: (1) activation in water of an amino acid presumably as its N-carboxyanhydride (NCA) using 1,1'-carbonyldiimidazole (CDI), and (2) subsequent condensation of the activated amino acid-NCA in the presence of a thiol. With this method citrulline peptide thioesters containing up to 10 amino acid residues were prepared in a single reaction. This aqueous synthetic method provides a simple way to prepare peptide thioesters for studies of peptide replication involving ligation of peptide thioesters on peptide templates. The relevance of peptide replication to the origin-of-life process is supported by previous studies showing that amino acid thioesters (peptide thioester precursors) can be synthesized under prebiotic conditions by reaction of small sugars with ammonia and a thiol.

Amino Acids↗

Interpretation of the results of investigating molecular fossils.

The difficulties and possible errors in interpreting the results of investigating molecular fossils within the scope of the problem of chemical evolution and origin of life on the earth are examined. These difficulties can be largely overcome on the basis of modeling processes of the transformation of organic matter under different geological conditions.

Amino Acids↗

The reactions of nitrogen heterocycles with acrolein: scope and prebiotic significance.

It has been suggested that life began with a self-replicating RNA molecule. However, after much research into the prebiotic synthesis of RNA, the difficulties encountered have lead some to hypothesize that RNA was preceded by a simpler molecule, one more easily synthesized prebiotically. Many of the proposed alternative molecules are based on acrolein, since it reacts readily with nucleophiles, such as the nucleobases, via Michael addition and is readily synthesized from formaldehyde and acetaldehyde. Reports regarding the reactions of nucleobases with concentrated acrolein solutions suggest that this is a plausible reaction mechanism, though there are also reports that the "incorrect" isomers are obtained. The scope and kinetics of the reaction of acrolein with various nitrogen heterocycles are reported here. Reactions of pyrimidines often give N(1) adducts as the major products. Reactions of purines often give N(9) adducts in good yield. The reactions are rapid under neutral to slightly alkaline conditions, and proceed at low temperatures and dilutions. The implications of these findings for the origin of life are discussed.

Acrolein↗

The sugar model: autocatalytic activity of the triose-ammonia reaction.

Reaction of triose sugars with ammonia under anaerobic conditions yielded autocatalytic products. The autocatalytic behavior of the products was examined by measuring the effect of the crude triose-ammonia reaction product on the kinetics of a second identical triose-ammonia reaction. The reaction product showed autocatalytic activity by increasing both the rate of disappearance of triose and the rate of formation of pyruvaldehyde, the product of triose dehydration. This synthetic process is considered a reasonable model of origin-of-life chemistry because it uses plausible prebiotic substrates, and resembles modern biosynthesis by employing the energized carbon groups of sugars to drive the synthesis of autocatalytic molecules.

Ammonia↗

Biological nitrogen fixation under primordial Martian partial pressures of dinitrogen.

Early Earth and early Mars were similar enough such that past geochemical and climatic conditions on Mars may have also been favorable for the origin of life. However, one of the most striking differences between the two planets was the low partial pressure of dinitrogen (pN2) on early Mars (18 mb). On Earth, nitrogen is a key biological element and in many ecosystems the low availability of fixed nitrogen compounds is the main factor limiting growth. Biological fixation of dinitrogen on Earth is a crucial source of fixed nitrogen. Could the low availability of dinitrogen in the primordial Martian atmosphere have prevented the existence, or evolution of Martian microbiota? Azotobacter vinelandii and Azomonas agilis were grown in nitrogen free synthetic medium under various partial pressures of dinitrogen ranging from 780-0 mb (total atmosphere=1 bar). Below 400 mb the biomass, cell number, and growth rate decreased with decreasing pN2. Both microorganisms were capable of growth at a pN2 as low as 5 mb, but no growth was observed at a pN2 < or = 1 mb. The data appear to indicate that biological nitrogen fixation could have occurred on primordial Mars (pN2=18 mb) making it possible for a biotic system to have played a role in the Martian nitrogen cycle. It is possible that nitrogen may have played a key role in the early evolution of life on Mars, and that later a lack of available nitrogen on that planet (currently, pN2=0.2 mb) may have been involved in its subsequent extinction.

Atmosphere↗

Prebiotic chemistry and the origin of the RNA world.

The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World. The central problem for origin-of-life studies, therefore, is to understand how a protein-free RNA World became established on the primitive Earth. We first review the literature on the prebiotic synthesis of the nucleotides, the nonenzymatic synthesis and copying of polynucleotides, and the selection of ribozyme catalysts of a kind that might have facilitated polynucleotide replication. This leads to a brief outline of the Molecular Biologists' Dream, an optimistic scenario for the origin of the RNA World. In the second part of the review we point out the many unresolved problems presented by the Molecular Biologists' Dream. This in turn leads to a discussion of genetic systems simpler than RNA that might have "invented" RNA. Finally, we review studies of prebiotic membrane formation.

Catalysis↗

A possible primordial peptide cycle.

alpha-Amino acids can undergo peptide formation by activation with carbon monoxide (CO) under hot aqueous conditions in the presence of freshly coprecipitated colloidal (Fe,Ni)S. We now show that CO-driven peptide formation proceeds concomitantly with CO-driven, N-terminal peptide degradation by racemizing N-terminal hydantoin and urea derivatives to alpha-amino acids. This establishes a peptide cycle with closely related anabolic and catabolic segments. The hydantoin derivative is a purin-related heterocycle. The (Fe,Ni)S-dependent urea hydrolysis could have been the evolutionary precursor of the nickelenzyme urease. The results support the theory of a chemoautotrophic origin of life with a CO-driven, (Fe,Ni)S-dependent primordial metabolism.

Amino Acids↗

The biological potential of Mars, the early Earth, and Europa.

The potential biomass that could have existed on Mars is constrained by the total amount of energy available to construct it. From an inventory of the available geochemical sources of energy, we estimate that from the time of the onset of the visible geologic record 4 b.y. ago to the present, as much as 20 g cm-2 of biota could have been created. This is the same amount that could have been constructed on the early Earth in only 100 million years. This indicates that there likely was sufficient energy available to support an origin of life on Mars but not sufficient energy to create a ubiquitous and lush biosphere. Similar calculations for Europa suggest that even less would have been available there.

Biomass↗

Between history and physics.

Biology has traditionally occupied a middle ground between the determinism of classical physics and the uncertainties of history. These issues are analyzed with respect to statistical laws which are applied to the prebiotic domain and strategy laws which characterize evolutionary biology. The differences in approach between biology and physics are discussed in detail. The origin of life is discussed in the context of physical chemical laws. A scenario for biogenesis is presented in terms of known molecular hardware. Evolutionary biology is then examined with respect to the kinds of laws that are possible in a domain where thermal fluctuations (mutations) have macroscopic effects. Game theory is employed to demonstrate the kinds of theory appropriate to this historical domain. The transition point between physics and history is the origin and development of the code. This is discussed and it is concluded that we are not yet able to assign the code to either the deterministic domain or to the arena of history.

Animals↗

The possible role of volcanic aquifers in prebiologic genesis of organic compounds and RNA.

In a volcanic aquifer, a wide range of physical and chemical conditions are not merely possible, but to be expected: relatively oxidizing and reducing environments both are present; hot and moderate temperatures can be expected; distillation and reflux conditions are probable to allow concentration of reactants, stimulation of reaction and fractionation of isotopes; apatite, hydroxides, clays and sulfide minerals are present to act as chromatographic media for separating compounds, to serve as catalytic surfaces and to provide potential energy sources; supersaturated precipitation of optically active crystals is reasonable, allowing for chromatographic separation of racemic mixtures by the resulting fixed chiral phase; and saturated and unsaturated conditions both are present for promotion of constructive reactions and inhibiting destructive hydrolysis reactions. Because the multitude of physical-chemical environments makes the setting robust with respect to circumventing commonly identified problems in origin-of-life theories, even if objections to details proposed herein are identified, the setting is favorable for devising alternatives. This paper describes a theory for the genesis of organic compounds, including RNA, in the mixing zone of juvenile and meteoric waters above a leaky semi-confined aquifer. Starting with basic reactants for best-guess conditions on Archean Earth, parallel sequences of specific reactions are proposed that culminate with RNA oligonucleotides, key molecules in contemporary life. All proposed reactions, or close analogues, are experimentally confirmed and all are set in plausible Archean conditions. Calculations indicate that the proposed reactions would yield C isotopic compositions that are consistent with observed biologic C.

Archaea↗

Unusual stable isotope ratios in amino acid and carboxylic acid extracts from the Murchison meteorite.

Much effort has been directed to analyses of organic compounds in carbonaceous chondrites because of their implications for organic chemical evolution and the origin of life. We have determined the isotopic composition of hydrogen, nitrogen and carbon in amino acid and monocarboxylic acid extracts from the Murchison meteorite. The unusually high D/H and 15N/14N ratios in the amino acid fraction (delta D = 1,370% after correction for isotope exchange; delta 15N = 90) are uniquely characteristic of known interstellar organic materials. The delta D value of the monocarboxylic acid fraction is lower (377%), but still consistent with an interstellar origin. These results confirm the extraterrestrial origin of both classes of compound, and provide the first evidence suggesting a direct relationship between the massive organo-synthesis occurring in interstellar clouds and the presence of pre-biotic compounds in primitive planetary bodies. The isotope data also bear on the historical problem of distinguishing indigenous material from terrestrial contaminants.

Amino Acids↗

Catalysis and prebiotic RNA synthesis.

The essential role of catalysis for the origins of life is discussed. The status of the prebiotic synthesis of 2',5'- and 3',5'-linked oligomers of RNA is reviewed. Examples of the role of metal ion and mineral catalysis in RNA oligomer formation are discussed.

Catalysis↗

The origin of optical asymmetry on earth.

The nature of optical isomerism, and the problem of the origin of optical asymmetry in relation to the origin of life are defined. Developments in particle physics, such as the discovery of parity non-conservation in weak interactions and more recently, of neutral currents, are described. Their significance is that there are a number of possible mechanisms whereby the fundamental asymmetry of matter could be reflected in a preference for one enantiomer over the other, and that, contrary to long-established views, optical isomers do not have identical energy contents: the difference, however, is estimated to be very small. Theories regarding the origin of optical asymmetry are classified in a two-dimensional matrix (origin by chance or due to already existing order; susceptible or not susceptible to experimental test). Recent experimental results and theoretical speculations are reviewed, and proposals are made for further experimental work.

Models, Chemical↗

A model for the origin of biological catalysis.

We propose a mathematical model for the next stage in the origin of life after that treated in our earlier work. At this stage we introduce the possibility of the modification of the environment by the information-containing entities and feedback between the environment and the population of macromolecules and hence provide a model for the development of the Eigen hypercycle.

Catalysis↗