Glycolysis at 75: is it time to tweak the first elucidated metabolic pathway in history?

摘要: The sequence of the glycolytic enzymatic reactions responsible for breakdown glucose into two trioses and further pyruvate or lactate was elucidated in 1940. For over seven decades it has been taught precisely way that first described by Embden, Meyerhof Parnas. Accordingly, different outcomes were proposed; aerobic one with as final product, anaerobic one, identical to glycolysis except additional step, reduction lactate. While presented mitochondrial substrate tricarboxylic acid cycle, regularly vilified a useless frequently toxic end product glycolysis. Several studies 1980s have shown both muscle brain tissues are capable oxidizing utilizing an energy substrate, thus challenging monocarboxylate's ill reputation. Expectedly, these findings met great skepticism doubts could play any role bioenergetics. Despite many from 1920s 1930s clearly showed ability tissue oxidize lactate, even investigators who published them assumed oxidation simply clearing mechanism this end-product (Schurr, 2006, 2014). Nevertheless, past monocarboxylate transporters (MCTs) identified localized cellular membranes existence receptor also suggested (Bergersen Gjedde, 2012). Both direct indirect evidence now indicate enzyme dehydrogenase (LDH) resides not only cytosol, part pathway machinery, but outer membrane. form oxidizes concomitantly produces reducing agent NADH (Passarella et al., 2014; Rogatzki 2015). These shed light on major drawback originally proposed version i.e., its inability regenerate NAD+, contrast features cyclical NAD+upon cytosolic LDH. malate-aspartate shuttle (MAS), redox alternative NAD+ generation However, necessity MAS fulfill such function be questioned if always proceeded end-products, when alternative, lactate-malate-aspartate (Kane, 2014) is considered. An dilemma presents, do erythrocytes, which despite highly environment end-product. Meanwhile, several other functions (Chambers Galow Hertz Brooks Martin, 2015; Goodwin decades, choice measuring rate State III respiration employing oxygen electrode. recently can used too (de Bari 2008; Passarella 2008, Additional experiments designed provide insight metabolism. example, would addition mitochondria ruptured red blood cells switch their produce instead lactate?