Krebs studies

Next, Hans Krebs studied the interrelationships between the oxidative metabolism of different organic acids. For his experiments he used slices of pigeon flight muscle, which are particularly active in oxidative metabolism. He... 

In 1932 Krebs was studying the rates of oxidation of small organic acids by kidney and liver tissue. Only a few substances were active in these experiments —notably succinate, fumarate, acetate, malate, and citrate (Figure 20.2). Later it was found that oxaloacetate could be made from pyruvate in such tissues, and that it could be further oxidized like the other dicarboxylic acids. 

Takaluoma T, Sakkinen T, Bajorek T, Laitinen RS, Krebs B, Conrad H, Conrad O (2007) Computational study of hybrid chalcogenoborate anions. J Mol Struct (THEOCHEM) 821 1-8... 

Dipartimento di Chimlca Organica e Industriale, Universrta degli Studi di Parma, Parco Area delle Scienze, 17/A, 43100 Parma, Italy tCentre for Chemical Biology, Krebs Institute for Biomolecular Science, Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom... 

Hamza, M., Lloveras,J., Ribbes, G., Soula, G. and Douste-Blazy, L. (1983) An in vitro study of hemicholinium-3 on phospholipid metabolism of Krebs II ascites cells. Biochemical Pharmacology 32, 1893—1897. 

There are also voices critical of the rTCA cycle Davis S. Ross has studied kinetic and thermodynamic data and concludes that the reductive, enzyme-free Krebs cycle (in this case the sequence acetate-pyruvate-oxalacetate-malate) was not suitable as an important, basic reaction in the life evolution process. Data on the Pt-catalysed reduction of carbonyl groups by phosphinate show that the rate of the reaction from pyruvate to malate is much too low to be of importance for the rTCA cycle. In addition, the energy barrier for the formation of pyruvate from acetate is much too high (Ross, 2007). 

The application of forward chemical genetics to studies of translation provides an opportunity to identify small molecules that inhibit or stimulate this process without any underlying assumptions as to which step is most amenable to targeting by the chemical libraries under consideration. The opportunity exists to identify novel factors involved in translation, unravel new activities of known translation initiation factors, or characterize shortlived intermediates that are frozen by the small molecule inhibitor. We have undertaken a forward chemical genetic approach to identify small molecules that inhibit or stimulate translation in extracts prepared from Krebs-2 ascites cells (Novae et al., 2004). These screens have led to the identification of several novel inhibitors of translation initiation and elongation (Bordeleau et al., 2005, 2006 Robert et al., 2006a,b). 

Introduction of photoelectric cells led to the replacement of the Duboscq colorimeter and so to quantitative spectrophotometric methods of analysis which met biochemical requirements. This introduction of spectrophotometry as a routine procedure was one of the earliest technological advances underpinning the elucidation of biochemical pathways between 1930-1960. Micromanometric methods also became available about the same time, and offered a means to measure cell respiration. Manometry was developed in Warburg s laboratory in Berlin and was one of the main techniques used by H.A. Krebs in his studies on the citric acid and urea cycles (Chapters 5 and 6). 

When his studies on carbohydrate oxidation restarted in Sheffield, Krebs experiments included studies on the anaerobic dismutation of pyruvate by bacteria and various animal tissues. Assuming the role for the dicarboxylic acids postulated by Szent-Gyorgi, the main question was the route by which the carbon atoms of pyruvate were converted to succinate. In May 1936 Krebs had observed that if 2-oxoglutarate was added to pyruvate, the yield of succinate was enormously increased. In his notebook written that year (Holmes, 1993) Krebs postulated ... 

Lohman discovered ATP in muscles. Krebs and Henseleit. The urea cycle. Svedberg began studies with the ultracentrifuge. 

Drs. Mary Gale, Brian Lloyd, and the late Hugh Sinclair helped us with references to early studies on nutrition Mr. Reg Hems and Dr. Dereck Williamson recounted their memories of working with Sir Hans Krebs and Dr. F. L. Holmes very kindly allowed us to read in manuscript the first volume of his authoritative work on Krebs. The late Professors Bill Paton and David Whitteridge directed us to important references in the history of physiology. Professor Bradford, the... 

Isotopes were not available in van t Hoff s day. My student generation was taught that an asymmetric carbon atom was a carbon atom attached to 4 chemically different groups. When isotopes of carbon, UC and 13C, were first applied as tracers to study carbohydrate metabolism, the entire emphasis was on the chemical similarity of 11C and 13C to the more abundant isotope 12C. Thus, it was of pressing interest to determine whether CO 2 participated in the oxidation of carbohydrate in animal tissues, a conclusion strongly suggested by the demonstration in Krebs laboratory, that pyruvate and oxalacetate behaved alike in pigeon liver, and by Wood and Werkman s earlier demonstration that some he-... 

Muscle glycogen phosphorylase is one of the most well studied enzymes and was also one of the first enzymes discovered to be controlled by reversible phosphorylation (by E.G. Krebs and E. Fischer in 1956). Phosphorylase is also controlled allosterically by ATP, AMP, glucose and glucose-6-phosphate. Structurally, muscle glycogen phosphorylase is similar to its hepatic isoenzyme counterpart composed of identical subunits each with a molecular mass of approximately 110 kDa. To achieve full activity, the enzyme requires the binding of one molecule of pyridoxal phosphate, the active form of vitamin B6, to each subunit. 

More than 55 alkaloids have been isolated from peyote. Mescaline (3,4,5-trimethoxy-j8-phenethylamine) is the primary psychoactive alkaloid of the peyote cactus, and by far the one that has been most studied (figure 9.6). These may be categorized into phenethylamines (including mescaline), isoquinolones, and Krebs acid conjugates. See table 9.2 for a partial list of peyote alkaloids. 

Figure B2(i) The pathway for conversion of proline and alanine in the flight muscle of the tsetse fly the major ATP-generating pathway. Alanine aminotransferase is essential for the proline oxidation pathway in order for glutamate to enter the Krebs cycle as oxoglutarate and pyruvate to be converted to alanine, the end of the pathway. It is assumed that the pathway is the same for the Colorado beetle, but no studies have been reported.

In any cell that depends on aerobic metabolism, if the rate of ATP utilisation increases, the rate of the Krebs cycle, electron transfer and oxidative phosphorylation must also increase. The mechanism of regulation discussed here is for mammalian skeletal muscle since, to provide sufficient ATP to maintain the maximal power output, at least a 50-fold increase in flux through the cycle is required so that the mechanism is easier to study (Figure 9.22). 

The work of Krebs and Wunderlich ( ) has been followed by a number of studies (3,13,15-20), demonstrating that particle size fractionation will also occur with a porous matrix. In this case,... 

Corresponding author Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, Western Bank, Sheffield SIO 2TN, UK. 

Critical for predictivity in a recent comprehensive study was the number and choice of parameters measured [4]. Early, sublethal effects on cell proliferation, cell morphology and mitochondria occurred consistently and ubiquitously with toxicity and when used collectively were most diagnostic. It is noteworthy that the toxicity of many drugs is attributable to various mitochondrial targets, including oxidative phosphorylation, fatty acid oxidation, Krebs cycling, membrane transport, permeability transition pore, proliferation and oxidative stress (Table 14.4). 

---