Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from Burkholderia cenocepacia.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a key enzyme in endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via the mevalonate pathway in other eukaryotes, archaea and some eubacteria. In most organisms that express this enzyme, it catalyzes the NAD(P)H-dependent reduction of HMG-CoA to mevalonate. We have cloned and characterized the 6x-His-tagged HMGR from the opportunistic lung pathogen Burkholderia cenocepacia. Kinetic characterization shows that the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme. This hypothesis is supported by the fact that the Burkholderia cenocepacia genome lacks the genes for the downstream enzymes of the mevalonate pathway. The enzyme exhibits positive cooperativity toward the substrates of the reductive reaction, but the oxidative reaction exhibits unusual double-saturation kinetics, distinctive among characterized HMG-CoA reductases. The unusual kinetics may arise from the presence of multiple active oligomeric states, each with different Vmax values.

Acquired Long QT Syndrome after Acute Myocardial Infarction: A Rare but Potentially Fatal Entity.

Acquired long QT syndrome is typically caused by medications, electrolyte disturbances, bradycardia, or catastrophic central nervous system events. We report a case of myocardial infarction-related acquired long QT syndrome in a 58-year-old woman that had no clear cause and progressed to torsades de pointes requiring treatment with isoproterenol and magnesium. Despite negative results of DNA testing against a known panel of genetic mutations and polymorphisms associated with long QT syndrome, the patient's family history of fatal cardiac disease suggests a predisposing genetic component. This report serves to remind clinicians of this potentially fatal ventricular arrhythmia after myocardial infarction.

Health disparities and underserved populations: a potential solution, medical school partnerships with free clinics to improve curriculum.

Health-care educators share the social responsibility to teach medical students about social determinants of health and health-care disparities and subsequently to encourage medical students to pursue residencies in primary care and medical practice in underserved communities. Free clinics provide care to underserved communities, yet collaborative partnerships with such organizations remain largely untapped by medical schools. Free clinics and medical schools in 10 US states demonstrate that such partnerships are geographically feasible and have the potential to mutually benefit both organizational types. As supported by prior research, students exposed to underserved populations may be more likely to pursue primary care fields and practice in underserved communities, improving health-care infrastructure.