Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states. The current review focused on the underlying mechanisms of altered BCAA catabolism and its contribution to the pathogenesis of a numerous pathological conditions such as diabetes, heart failure and cancer. In addition, we summarize findings that indicate that the recovery of the dysregulated BCAA catabolism may be associated with an improved outcome and the prevention of serious disease complications.

NMR‐based metabonomic analysis is a well‐established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter‐individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR‐based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N‐oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N‐oxide and an unidentified metabolite (δ 3.78). Copyright © 2007 John Wiley & Sons, Ltd.

Rhabdomyolysis is a common clinical and laboratory syndrome, resulting from skeletal muscle injury, that leads to the release of potentially toxic muscle cell contents, specifically myoglobin, into the plasma ( 1)( 2). Rhabdomyolysis can be induced by many different mechanisms and has been implicated as a major cause of acute renal failure. However, when correct treatment is provided, it is usually reversible. Acute tubular necrosis after rhabdomyolysis does not always appear to parallel the degree of muscle damage, but it may be related to other factors that potentiate the effects of myoglobinuria, such as hypotension, acidosis, and volume depletion. The pathophysiology of the renal injury is not fully understood, but it probably includes a combination of hypoperfusion/ischemia, iron tubular cytotoxicity, and cast formation potentially leading to proximal tubular necrosis and acute renal failure.