RESUMEN
The leucine catabolism pathway intermediate, trans-3-methylglutaconyl (3MGC) CoA, is considered to be the precursor of 3MGC acid, a urinary organic acid associated with specific inborn errors of metabolism (IEM). trans-3MGC CoA is an unstable molecule that can undergo a sequence of non-enzymatic chemical reactions that lead to either 3MGC acid or protein 3MGCylation. Herein, the susceptibility of trans-3MGC CoA to protein 3MGCylation was investigated. trans-3MGC CoA was generated through the activity of recombinant 3-methylcrotonyl CoA carboxylase (3MCCCase). Following enzyme incubations, reaction mixtures were spin-filtered to remove 3MCCCase. The recovered filtrates, containing trans-3MGC CoA, were then incubated in the presence of bovine serum albumin (BSA). Following this, sample aliquots were subjected to α-3MGC IgG immunoblot analysis to probe for 3MGCylated BSA. Experiments revealed a positive correlation between trans-3MGC CoA incubation temperature and 3MGCylated BSA immunoblot signal intensity. A similar correlation was observed between incubation time and 3MGCylated BSA immunoblot signal intensity. When trans-3MGC CoA hydratase (AUH) was included in incubations containing trans-3MGC CoA and BSA, 3MGCylated BSA immunoblot signal intensity decreased. Evidence that protein 3MGCylation occurs in vivo was obtained in studies with liver-specific 3-hydroxy-3-methylglutaryl (HMG) CoA lyase knockout mice. Therefore, trans-3MGC CoA is a reactive, potentially toxic metabolite, and under normal physiological conditions, lowering trans-3MGC CoA levels via AUH-mediated hydration to HMG CoA protects against aberrant non-enzymatic chemical reactions that lead to protein 3MGCylation and 3MGC acid production.
RESUMEN
CONTEXT: Studies suggest that the mass media is a common source of cancer information for the public. However, the quality of cancer information through various print outlets has not been extensively investigated. OBJECTIVES: To assess the accuracy of cancer information in a retrospective sample of Ontario daily newspapers as well as to determine the amount of mobilizing (enabling) information about community resources for cancer. METHODS AND RESULTS: Of 1,027 articles on cancer for 1991, drawn from the 5 highest and 5 lowest circulating newspapers, a random 30% sample (306 articles) was obtained. Only 40 articles had traceable citations (journal name, name of researcher, name of educational institution, or direct quotes from identifiable sources). Of these, 47.5% had misleading titles and 55% included erroneous information or omitted important study results. Only 13 (6.9%) included mobilizing information regarding prevention, diagnosis, treatment or support. INTERPRETATION: Cancer information in newspapers contain frequent inaccuracies and fail to provide mobilizing information. Inaccurate newspaper information about cancer is of concern if the public relies on this channel for at least part of their health knowledge.