Learn More
We have previously described the isolation and sequencing of cDNA clones encoding flavin-containing monooxygenases (FMOs) 1 and 4 of man [Dolphin, C., Shephard, E. A., Povey, S., Palmer, C. N. A., Ziegler, D. M., Ayesh, R., Smith, R. L. & Phillips, I. R. (1991) J. Biol. Chem. 266, 12379-12385; Dolphin, C., Shephard E. A., Povey, S., Smith, R. L. & Phillips,(More)
Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain(More)
This review outlines the molecular sensors that reprogram cellular metabolism in response to the ketogenic diet (KD). Special emphasis is placed on the fasting-, fatty acid- and drug-activated transcription factor, peroxisome proliferator-activated receptor alpha (PPARalpha). The KD causes a switch to ketogenesis that is coordinated with an array of changes(More)
The metabolic capability for the complete oxidation of glucose, i.e. aerobic glycolysis, is highly developed in the brains of neurologically mature (precocial) species at birth, whereas this activity is severely limited in the brains of neurologically immature (non-precocial) species such as the rat and human. The latter utilize a mixture of glucose and(More)
The contractile cells in the heart (the cardiac myocytes) are terminally differentiated. In response to pathophysiological stresses, cardiac myocytes undergo hypertrophic growth or apoptosis, responses associated with the development of cardiac pathologies. There has been much effort expended in gaining an understanding of the stimuli which promote these(More)
Cardiac myocyte death, whether through necrotic or apoptotic mechanisms, is a contributing factor to many cardiac pathologies. Although necrosis and apoptosis are the widely accepted forms of cell death, they may utilize the same cell death machinery. The environment within the cell probably dictates the final outcome, producing a spectrum of response(More)
We report the isolation, by RT-PCR, of partial cDNAs encoding the rat peroxisome proliferator-activated receptor (PPAR) isoforms PPAR alpha, PPAR beta, and PPAR gamma and the rat retinoid X receptor (RXR) isoforms RXR alpha, RXR beta, and RXR gamma. These cDNAs were used to generate antisense RNA probes to permit analysis, by the highly sensitive and(More)
Inhibition of glycogen synthase kinase 3beta (GSK3beta) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3alpha (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3beta(More)
We analysed the structure of the white locus of Drosophila melanogaster in a family of related white mutants. The white-one mutant has bleach white eyes, and a Doc transposable element is inserted into the promotor region of the white locus. The DNA sequence of this Doc insertion was determined, and showed it to be closely related to other Drosophila(More)
The ketogenic diet is a clinically and experimentally effective anti-epileptic treatment whose molecular mechanism(s) of action remain to be elucidated. As a first step in defining its effects on regulation of fatty acid oxidation and ketogenesis at the genetic level, we have administered to rats: (1) a calorie-restricted ketogenic diet (KCR); (2) a(More)