Metabolism in the age of ‘omes’

Abstract

SummaryMuch research in comparative physiology is now performed using ʻomicsʼ tools and many results are interpreted in terms of the effects of changes in gene expression on energy metabolism. However, ʻmetabolismʼ is a complex phenomenon that spans multiple levels of biological organization. In addition rates and directions of flux change dynamically under various physiological circumstances. Within cells, message level cannot be equated with protein level because multiple mechanisms are at play in the ʻregulatory hierarchyʼ from gene to mRNA to enzyme protein. This results in many documented instances wherein change in mRNA levels and change in enzyme levels are unrelated. It is also known from metabolic control analysis that the influence of single steps in pathways on flux is often small. Flux is a system property and its control tends to be distributed among multiple steps. Consequently, change in enzyme levels cannot be equated with change in flux. Approaches developed by Hans Westerhoff and colleagues, called ʻhierarchical regulation analysisʼ, allow quantitative determination of the extent to which ʻhierarchical regulationʼ, involving change in enzyme level, and ʻmetabolic regulationʼ, involving the modulation of the activity of preexisting enzyme, regulate flux. We outline these approaches and provide examples to show their applicability to problems of interest to comparative physiologists.

The effects of temperature on aerobic metabolism: towards a mechanistic understanding of the responses of ectotherms to a changing environment

“…The analyses discussed above have attempted to model the systems properties of biological networks using data on the activity of proteins measured in vitro. In vivo, flux through metabolic pathways is most often controlled by variation in the concentrations of substrates, products or allosteric effectors, in what has been termed 'metabolic regulation' (ter Kuile and Westerhoff, 2001;Suarez and Moyes, 2012). Indeed, studies of the thermal dependence of glycolytic flux in yeast suggest that metabolic regulation is the dominant force in determining the response of pathway flux as temperature increases (Postmus et al, 2008).…”

Experimental ocean acidification alters the allocation of metabolic energy

“…For example, recent large-scale transcriptomic and proteomic studies of the expression of ∼5,000 genes and their corresponding proteins have shown that changes in gene expression are not good measures of protein abundance (40). Even when mRNA predicts protein abundance, physiologically relevant protein activity can vary substantially from patterns of gene expression or protein abundance (41)(42)(43)(44). For comparative studies of marine organisms that lack comprehensive and simultaneous quantification of transcriptomes and proteomes (40), analyses that infer physiological activity from measurements of gene expression should be interpreted with caution.…”

Temperature during embryonic development has persistent effects on metabolic enzymes in the muscle of zebrafish

“…These observations should be partly due to the well-known kinetic effects of temperature on reaction rates, but could also result from effects on the various physiological factors that control metabolism. Metabolic rate and oxygen consumption are system-level processes that are influenced by all steps in the pathway of oxygen and fuel delivery and oxidation, including the activity of metabolic enzymes and the abundance of mitochondria (Suarez and Moyes, 2012). In this regard, T E has been shown to alter mitochondrial abundance in the muscle of larvae from several fish species (Vieira and Johnston, 1992;Brooks and Johnston, 1993).…”