Catabolic pathways-for example glycolysis, oxidative phosphorylation via tricarboxylic acid cycle (TCA) and lipogenesis-involve the breakdown of major nutrients (glucose, amino acids and fatty acids) to generate energy, which is either stored for later use or released as heat. Anabolic pathways then build macromolecules out of the products of catabolism, which are building blocks for cell structures and help to maintain the cell. Cells also produce lactate, ammonia, carbon dioxide and reactive oxygen species (ROS) as by-products of the metabolic breakdown of sugars, fats and proteins. Emerging studies have revealed a functional role for many of these metabolic by-products. For many years, lactate was seen as the metabolic waste product of glycolytic metabolism however, new roles for lactate in the tumour microenvironment as a metabolic fuel, modulator of extracellular pH or as a signalling molecule have emerged.
Ammonia, generated as a by-product of proteins that are broken into amino acids by amino acid lyases and nucleotide deaminases, is toxic at high concentrations and, thus, gets further converted into urea. ROS, mainly generated through NADPH oxidase (NOX4) and through electron leak from electron transport chain (ETC) complexes, are potent mitogens that promote proliferation, differentiation and migration. Unlike normal cells, cancer cells rewire their cellular metabolism to promote growth and survival and thus have different nutritional requirements, and many different cancer types exhibit similar metabolic alterations. 3 This change was originally thought to be due to defective oxidation caused by mitochondrial dysfunction, but has now been partly explained biologically 4, 5: the rapid uptake and metabolism of glucose allows cells to feed several non-mitochondrial pathways, such as the pentose phosphate pathway, which produces ribose for nucleotides and NADPH for reductive biosynthesis, and the hexosamine pathway, which is required for protein glycosylation and glycerol synthesis for production of complex lipids.ġ, 2 The Warburg effect, for example, is a change in the metabolism of most cancer cells that enables them to convert glucose into lactate, even in the presence of abundant oxygen-in a process known as aerobic glycolysis. The Warburg effect might support anabolic metabolism indirectly while maintaining large pools of glycolytic intermediates that favour engagement of the pentose phosphate pathway and other biosynthetic pathways inside the cell. 6 Although the exact mechanism(s) of altered metabolism and its effect on cancer behaviour is unknown, an increased awareness of the dependencies of cancer cells on specific metabolic pathways and the potential for therapeutically exploiting these dependencies have led to an interest in better understanding the underlying processes. Several tools have been designed to assess metabolism without disturbing the system. Professional Translations provides a full range of professional translation services, delivered efficiently and with the right terminology. Advances in nuclear magnetic resonance and mass spectroscopy have helped to quantify the carbon influx of the central metabolic pathways (e.g. TCA cycle, glycolysis and pentose phosphate pathway) in mammalian systems, and this approach has been instrumental in demonstrating that the metabolism of a tumour depends on factors such as the tissue of origin, the tumour microenvironment (TME), the level of hypoxia, and so on. The intellectus pro stu isto has as its first object ens in quantum ens and so it is open to the totatity of reality.īT - Mondo uomo Dio.Furthermore, tumour cells appear to turn on different programs of metabolic pathways to generate ATP, proteins, nucleotides and lipids for cellular proliferation compared with normal cells. John Duns Scotus distinguishes the human intellect in intellectus pro statu isto and intellectus ex natura potentiae. The intellectus pro stu isto has as its first object ens in quantum ens and so it is open to the totatity of reality.ĪB - In the medieval philosphy the problem of foundation is to determinate the ens primum cognitum, that is the first object for human intellect. N2 - In the medieval philosphy the problem of foundation is to determinate the ens primum cognitum, that is the first object for human intellect. T1 - Giovanni Duns Scoto e il problema del fondamento