Comparative enzymology-new insights from studies of an "old" enzyme, lactate dehydrogenase
Comparative enzymology explores the molecular mechanisms that alter the properties of enzymes to best fit and adapt them to the biotic demands and abiotic stresses that affect the cellular environment in which these protein catalysts function. For many years, comparative enzymology was primarily concerned with analyzing enzyme functional properties (e.g. substrate affinities, allosteric effectors, responses to temperature or pH, stabilizers, denaturants, etc.) in order to determine how enzyme properties were optimized to function under changing conditions. More recently it became apparent that posttranslational modifications of enzymes play a huge role in metabolic regulation. At first, such modifications appeared to target just crucial regulatory enzymes but recent work is showing that many dehydrogenases are also targets of posttranslational modification leading to substantial changes in enzyme properties. The present article focuses in particular on lactate dehydrogenase (LDH) showing that stress-induced changes in enzyme properties can be linked with reversible posttranslational modifications; e.g. changes in the phosphorylation state of LDH occur in response to dehydration stress in frogs and anoxia exposure of turtles and snails. Furthermore, these studies show that LDH is also a target of other posttranslational modifications including acetylation, methylation and ubiquitination that change in response to anoxia or dehydration stress. Selected new methods for exploring posttranslational modifications of dehydrogenases are discussed and new challenges for the future of comparative enzymology are presented that will help to achieve a deeper understanding of biochemical adaptation through enzyme regulation.
|Keywords||Enzyme adaptation, Hypometabolism, Lactate dehydrogenase, Metabolic regulation, Posttranslational modification, Protein acetylation, Reversible protein phosphorylation|
|Journal||Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology|
Storey, K. (2016). Comparative enzymology-new insights from studies of an "old" enzyme, lactate dehydrogenase. Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology, 199, 13–20. doi:10.1016/j.cbpb.2015.12.004