Metabolism-first

The still open question, Information or metabolism first has again been discussed by Robert Shapiro. In an article with the title Did This Molecule Start Life A Simple Origin for Life , he again stresses that it is improbable that life could have begun in an RNA world (referred to here as RNA-first ). Shapiro offers his own suggestion in the metabolism debate he assumes that cyclical processes, occurring in small compartments, lead from small molecules to systems of higher complexity. The Shapiro model takes into account aspects of the approaches and hypotheses proposed by Wachtershauser (see Sect. 7.3), de Duve (see Sect. 7.4) and Kauffmann (see Sect. 9.3). In order to avoid one-sidedness, Shapiro s article is accompanied by a short reply An RNA-First Researcher Replies . In this way, the reader is shown in a clear and understandable manner what the differences between the two approaches are (Shapiro, 2007). 

The wide gap between the two opposing theories, replication first and metabolism first , was analysed by Pross from the Ben Gurion University of the Negev (Israel). Pross concludes that replication came first He is convinced that a causality between the two theories can only be established if it is assumed that the replication-first thesis is correct. His analysis also shows that more of the experimental results and theoretical rationales favour the replication thesis. The author finds his assumption justified that life processes are strongly kinetically controlled and that the development of metabolic pathways can only be understood if life is considered as a manifestation of replicative chemistry (Pross, 2004). 

VON BERTALANFFY, L., Basic concepts in quantitative biology of metabolism. In Quantitative Biology of Metabolism - First International Symposium (O. Kinneand A. Locker, eds.), Helgoland. 1964, (vol 9), pp. 5-37. 

Alcohol, taken orally, is absorbed in the stomach but mostly from the small intestine into the bloodstream. It first reaches the liver, where some alcohol is immediately metabolized (first-pass metabolism) by the enzyme alcohol dehydrogenase. Alcohol is a water-soluble chemical and distributes throughout body fluids but not readily into body fat. Females, who naturally have more lipid (fat) tissue per pound of mass, will have a higher BAG than males after consuming the same amount of alcohol. 

First-pass metabolism (first-pass effect) The passage of the drug from the portal circulation into hepatocytes and conversion there into metabolites. These metabolites may have a pharmacological profile different from that of the parent drug. They are typically then excreted by the hepatocytes into the biliary system and pass back into the small bowel where enterohepatic recirculation may occur (e.g., benzodiazepines, bupropion, nefazodone, neuroleptics, tricyclic antidepressants). 

All you need to do, to see that clearly, is to look at that one additional observation involving oral activity. This drug, 5-MeO-MIPT, is several times more potent when taken orally than it is when smoked. 5-MeO-DMT is much less active orally than when it is smoked. As a matter of fact, it is not active at all when taken orally. No active oral level has ever been found. What a rich area for speculation. Preferential metabolism First pass goings-on Chemical change from pyrolysis in the pipe Different receptors Lipophilicity I am reminded of the quote from Mark Twain "I like science because it gives one such a wholesome return of conjecture from such a trifling investment of fact."... 

While the clinical use of MS/MS of hormonal steroids is new, metabolite analysis by gas chromatography (GC)-mass spectrometry (MS) has been available for 40 years, since few immunoassays were developed for urinary analytes. Profile analysis is a very powerful technique and it must be recognized that with few exceptions, all disorders of steroid synthesis and metabolism first had their metabolome defined... 

Distribution is the phase in which the compound is carried to tissues by the bloodstream or lymphatic system. Compounds are usually first absorbed into the portal venous system after oral administration, directing them to the liver where they may be removed (extracted/ metabolized) (first-pass effect). The blood (plasma) level reflects the concentration at the... 

The common ancestor of life was probably a chemoautotrophic hyperthermophilic anaerobe. This metabolism first theory assumes that life started with catalytic metal sulfide surface/compartments in a hydro thermal-vent setting in the Hadean... 

Efflux systems and presystemic metabolism are, beside other reasons, responsible for low bioavailability of orally administered drugs. Presystemic metabolism itself can be divided into three subtypes luminal metabolism, first-pass intestinal metabolism, and first-pass hepatic... 

Transdermal delivery is a noninvasive intravenous infusion of drug to maintain efficacious drug levels in the body for predictable and extended duration of activity. Diffusion-controlled transdermal systems are designed to deliver the therapeutic agent at a controlled rate from the device to and through the skin into the systemic circulation. This route of administration avoids unwanted presystemic metabolism (first-pass effect) in the GI tract and the liver. Patient satisfaction has been realized through decreased... 

Given how the DOM-Fe-P complex influences ecosystem structure, it is also likely that the DOM-Fe-P complex influences humic lake ecosystem function in terms of C metabolism. First, the bacterial conversion of dissolved C into biomass it is quite low, with an average of 25 % across a trophic gradient (del Giorgio et al., 1997). And despite the evidence that bacteria may be better equipped to acquire the Fe and P bound to DOM, the added energetic expenditure in acquiring these elements may result in a significant... 

SMALL-MOLECULE ( METABOLISM FIRST ) THEORIES OF LIFE S ORIGIN... 

That view of the origin of life has commonly been called metabolism first the absence of a genetic polymer has been equated with the lack of any mechanism for heredity. As we have seen, replicator theories center on the spontaneous formation of large, information-bearing organic polymers endowed with the ability to copy themselves. The hereditary information carried in the sequence of such a polymer is called a genome. 

Some versions of metabolism first schemes have drawn criticism in the literature.71,72 The schemes have assumed that a self-sustaining metabolic network must be autotrophic 73 that is, it must obtain its carbon supply entirely from carbon dioxide, rather than using carbon compounds made by abiotic processes (Sections 5.2.1 and 5.2.2). The assumption that chemicals in proposed reactions in the central metabolic cycle will be catalyzed by other compounds that participate in the cycle has also been questioned.74 Such features are attractive but not essential to the idea of life with small molecules. It has been argued that the objections can be met in principle by introducing a small number of assumptions 75... 

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