Adaptation of enzymes to temperature: searching for basic strategies

The pervasive influence of temperature on biological systems necessitates a suite of temperature-compensatory adaptations that span all levels of biological organization-from behaviour to fine-scale molecular structure. Beginning about 50 years ago, physiological studies conducted with whole organisms or isolated tissues, by such pioneers of comparative thermal physiology as V Ya. Alexandrov, T.H. Bullock, F.E.J. Fry, H. Precht, C.L. Prosser, and RE Scholander, began to document in detail the abilities of ectothermic animals to sustain relatively similar rates of metabolic activity at widely different temperatures of adaptation or acclimation. These studies naturally led to investigation of the roles played by enzymatic proteins in metabolic temperature compensation. Peter Hochachka's laboratory became an epicenter of this new focus in comparative physiology. The studies of the enzyme lactate dehydrogenase (LDH) that he initiated as a PhD student at Duke University in the mid-1960s and continued for several years at the University of British Columbia laid much of the foundation for subsequent studies of protein adaptation to temperature. Studies of orthologs of LDH have revealed the importance of conserving kinetic properties (catalytic rate constants (K-cat) and Michaelis-Menten constants (K-m)) and structural stability during adaptation to temperature, and recently have identified the types of amino acid substitutions causing this adaptive variation. The roles of pH and low-molecular-mass organic solutes (osmolytes) in conserving, the functional and structural properties of enzymes also have been elucidated using LDH. These studies, begun in Peter Hochachka's laboratory almost 40 years ago, have been instrumental in the development of a conceptual framework for the study of biochemical adaptation, a field whose origin can be traced largely to his creative influences. This framework emphasizes the complementary roles of three strategies of adaptation: (1) changes in amino acid sequence that cause adaptive variation in the kinetic properties and stabilities of proteins, (2) shifts in concentrations of proteins, which are mediated through changes in gene expression and protein turnover; and (3) changes in the milieu in which proteins function, which conserve the intrinsic properties of proteins established by their primary structure and modulate protein activity in response to physiological needs. This theoretical framework has helped guide research in adaptational biochemistry for many years and now stands poised to play a critical role in the post-genomic era, as physiologists grapple with the challenge of integrating the wealth of new data on gene sequences (genome), gene expression (transcriptome and proteome), and metabolic profiles (metabolome) into a realistic physiological context that takes into account the evolutionary histories and environmental relationships of species. (C) 2004 Elsevier Inc. All rights reserved.