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I. Introduction II. Transcriptional Control by Glucose A. Introduction B. Transcriptional regulation of metabolism by high glucose levels C. Transcriptional regulation of metabolism by low glucose levels III. Transcriptional Control [...]

In newborn errors of metabolism, biomarkers are urgently needed for disease screening, diagnosis, and monitoring of therapeutic interventions. This article describes a 2-step approach to discover metabolic markers, which involves [...]

Central nervous system (CNS) control of systemic nutrient homeostasis is a crucial but poorly understood metabolic regulatory axis. A new study (484-492) shows that rat insulin promoter (RIP)-expressing neurons in the hypothalamus regulate peripheral metabolic responses to both normal and high-fat diets through anti-inflammatory effects mediated by vagal innervation of the spleen., Despite being identified more than 150 years ago, the role of the CNS in systemic metabolism remains enigmatic, in large part due to scientific attention being lavished on, first, the [...]

We derive a general model, based on principles of biochemical kinetics and allometry, that characterizes the effects of temperature and body mass on metabolic rate. The model fits metabolic rates of microbes, ectotherms, endotherms (including those in hibernation), and plants in temperatures ranging from 0 ° to 40 ° C. Mass- and temperature-compensated resting metabolic rates of all organisms are similar: The lowest (for unicellular organisms and plants) is separated from the highest (for endothermic vertebrates) by a factor of about 20. Temperature and body size are primary determinants of biological time and ecological rotes., Metabolism sustains life. It is the process by which energy and materials are transformed within an organism and exchanged between the organism and its environment. Whole organism metabolic rate scales [...]

The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions., The pregnane X receptor (PXR; also known as NR1I2), a member of the nuclear receptor family of ligand-activated transcription factors, is a key regulator of cytochrome P450-3A (CYP3A) gene expression [...]

Ecologists who are trying to unravel the response of the terrestrial carbon cycle to rising atmospheric carbon dioxide concentration are faced with overwhelming issues of spatial and temporal scale. The [...]