Glycolytic Enzymes

Abstract All cells must burn fuels to drive the myriad of cellular processes necessary for life. The most important organic fuel is glucose, a stable and soluble sugar that is particularly well suited for its role in biology. Cellular combustion of glucose occurs in 10 well‐controlled steps in which six‐carbon glucose molecules are broken apart (literally ‘glycolysis’) into three‐carbon compounds. In the same process chemical energy is captured through the production of ATP (adenosine triphosphate), the hydrolysis of which powers many cellular processes. The 10 enzymes which catalyse the steps of glycolysis are exceptionally well characterised. They provide a fascinating array of enzymes that have been perfected over long evolution to carry out their tasks swiftly, efficiently and with finely tuned control. Key concepts: Glycolysis is an ancient pathway that is present at least in part in all organisms. Ten enzymes catalyse the reactions of the glycolytic pathway. Many enzymes occur as isoenzymes in different tissues or in response to different metabolic conditions. Hexokinase activity is regulated by product inhibition. A hinge‐bending motion of the two‐lobed structures of hexokinase and phosphoglycerate kinase is induced by substrate binding, and is required to position the substrates correctly for catalysis. Several reactions of the glycolytic pathway can be catalysed by pairs of nonhomologous enzymes (i.e. glucose‐phosphate isomerase, aldolase, glyceraldehyde‐3‐phosphate dehydrogenase and phosphoglycerate mutase). Phosphofructokinase occurs as two distantly related types that use different phospho donors: ATP or inorganic pyrophosphate. Activities of phosphofructokinase and pyruvate kinase are allosterically regulated. A conserved protein fold of eight parallel β‐strands and eight parallel α helices, first identified in triosephosphate isomerase and therefore known as the ‘TIM barrel’ is found in several glycolytic enzymes and occurs in approximately 10% of all enzymes. The Rossmann fold that occurs in many nucleotide‐binding proteins was first identified in glyceraldehyde‐3‐phosphate dehydrogenase. Pyruvate kinase activity is sometimes regulated by posttranslational phosphorylation.