what are the consequences of PKM2 expression?(select all that apply).1.accumulation of glycolytic intermediates used for anabolic pathways.2.increased electron transport activity in mitochondria.3.increased mutations in p53 gene.4.increased ATP production.5.increased flux through pentose phosphate pathway
Answers
Explanation:
Focus on the Warburg effect, initially descriptive of increased glycolysis in cancer cells, has served to illuminate mitochondrial function in many other pathologies. This review explores our current understanding of the Warburg effect’s role in cancer, diabetes and ageing. We highlight how it can be regulated through a chain of oncogenic events, as a chosen response to impaired glucose metabolism or by chance acquisition of genetic changes associated with ageing. Such chain, choice or chance perspectives can be extended to help understand neurodegeneration, such as Alzheimer’s disease, providing clues with scope for therapeutic intervention. It is anticipated that exploration of Warburg effect pathways in extreme conditions, such as deep space, will provide further insights crucial for comprehending complex metabolic diseases, a frontier for medicine that remains equally significant for humanity in space and on earth.
Keywords: Warburg effect, mitochondria, radiation, metabolism, neurodegenerative diseases, space biology
1. Introduction: What Is the Warburg Effect?
With the successful delivery of Mars Exploration Rovers (MER); Sojourner, Spirit (MER-A), Opportunity (MER-B) and Curiosity, plans for sending humans to Mars are in progress [1]. Beyond the considerable engineering challenges, pioneering habitation in hostile environments will require full awareness of the biological impact of galactic cosmic radiation. Like narratives describing the fate of fictional invaders from Mars [2], the final outcome will also crucially depend on a comprehensive understanding and appreciation of the microbial world. Endo-symbiotically intertwined in the evolutionary tree of eukaryotic life, mitochondria determine our overall metabolism [3]. In mammalian cells, though not all species, these ubiquitous and diverse organelles use oxygen (O2) as the terminal acceptor for anabolic processes, specializing our life to a dependency on oxic environments. Careful quantitative measurement of mitochondrial energy production mechanisms led to a hypothesis persisting for nearly a century as insightful for cellular stress responses to harsh environments and illness.
Dramatic changes in infant growth rate accompany the first breath of the newborn. The oxygen we breathe fuels the high energy-yielding oxyhydrogen gas reaction by which two molecules of hydrogen and one molecule of oxygen are converted to water, releasing −193 kJ/mol of energy under physiological conditions to fuel ATP synthesis from ADP and phosphate. An accompanying major source of cellular energy and new cell mass is glucose. Glycolysis breaks glucose down to pyruvate (Figure 1), that ultimately can be metabolized oxidatively to CO2 by a network of enzymes known as the tricarboxylic acid (TCA) cycle. Linking the metabolic pathways of glycolysis and the TCA cycle, a pyruvate dehydrogenase complex (PDC) made of three enzymatic proteins in the mitochondrial matrix breaks down pyruvate to form acetyl-CoA, releasing CO2 and NADH. Subsequently, during aerobic respiration, the TCA cycle coordinates catabolic breakdown of acetyl-CoA, releasing electron flow to the final O2 acceptor through a respiratory chain concomitantly generating a transiently stored proton gradient across the inner mitochondrial membrane. This gradient of electric potential energetically fuels oxidative phosphorylation (OXPHOS) mediated by the ATP synthase complex, generating ATP from ADP. Energy from the proton gradient can also be dissipated as heat through passive proton leakage or via uncoupling proteins [4].
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