Anabolism | EPFL Graph Search

Anabolism (əˈnæbəlɪzəm) is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect. Anabolism is usually synonymous with biosynthesis. Polymerization, an anabolic pathway used to build macromolecules such as nucleic acids, proteins, and polysaccharides, uses condensation reactions to join monomers. Macromolecules are created from smaller molecules using enzymes and cofactors. Anabolism is powered by catabolism, where large molecules are broken down into smaller parts and then used up in cellular respiration. Many anabolic processes are powered by the cleavage of adenosine triphosphate (ATP). Anabolism usually involves reduction and decreases entropy, making it unfavorable without energy input. The starting materials, called the precursor molecules, are joined using the chemical energy made available from hydrolyzing ATP, reducing the cofactors NAD+, NADP+, and FAD, or performing other favorable side reactions. Occasionally it can also be driven by entropy without energy input, in cases like the formation of the phospholipid bilayer of a cell, where hydrophobic interactions aggregate the molecules. The reducing agents NADH, NADPH, and FADH2, as well as metal ions, act as cofactors at various steps in anabolic pathways. NADH, NADPH, and FADH2 act as electron carriers, while charged metal ions within enzymes stabilize charged functional groups on substrates. Substrates for anabolism are mostly intermediates taken from catabolic pathways during periods of high energy charge in the cell. Anabolic processes build organs and tissues. These processes produce growth and differentiation of cells and increase in body size, a process that involves synthesis of complex molecules. Examples of anabolic processes include the growth and mineralization of bone and increases in muscle mass.

GLUT1 and GLUT3 in non-small cell lung cancer

Mark Jonathan Masin

While altered metabolism is a well-established tumor cell trait, the specifics of metabolic rewiring during cancer development and progression are yet to be fully understood. The Warburg effect, or aerobic glycolysis, has been described in a wide array of malignancies and has long been considered as an inefficient mean to fill energetic requirements. Emerging evidence however supports a role that extends beyond that, with glycolytic intermediates diverting to anabolic pathways to allow growth and proliferation. Importantly, the first and most critical rate-limiting step in glycolysis is glucose uptake. Fittingly, high affinity, high capacity glucose transporters such as GLUT1 and to a lesser extent GLUT3, are upregulated in cancer. Given the centrality of glycolysis in tumor biology and reported clinical observations relating to glucose transporter expression patterns, the present work focuses on characterizing the role of GLUT1 and GLUT3 in the context of non-small cell lung cancer (NSCLC), the most prevalent histological subtype of lung cancer. Linking glucose metabolism and a program involved in early steps of metastasis, part of the findings uncovers an aberrant expression of GLUT3 as integral to the epithelial-mesenchymal transition (EMT) in NSCLC. Indeed, a unique association between GLUT3 and a mesenchymal status is observed in a panel of human NSCLC cell lines. Furthermore, GLUT3 expression is increased during EMT by a mechanism that involves direct binding of EMT mediating transcription factor ZEB1 to the GLUT3 (SLC2A3) gene. Data also supports a functional role of GLUT3 in proliferation, as inhibiting GLUT3 expression reduces glucose import and proliferation of mesenchymal lung tumor cells, whereas ectopic expression in epithelial cells sustains proliferation in low glucose. In an analysis of a large microarray data collection of human NSCLC samples, GLUT3 expression is found to correlate with EMT markers, and is prognostic of poor overall survival. Taken collectively, the data reveal an important role for GLUT3 in lung cancer, when tumor cells loose their epithelial characteristics to become more invasive. Owing to the restricted expression of this transporter in healthy individuals, its presence in lung tumor cells may represent a noteworthy prospect for targeted therapy. The contrastingly ubiquitous nature of GLUT1 in normal and transformed tissue warrants in vivo investigation to determine expression patterns and contribution tumor development. To that end, generation of autochthonous lung cancer mouse models allows assessment of the effect of tumor exclusive GLUT1 loss. Ensuing preliminary results allude to a possible role of GLUT1 in specific histological lesions. The significance of this specificity is currently under investigation.

EPFL2015

GLUT1 and GLUT3 in non-small cell lung cancer

Mark Jonathan Masin

EPFL2015