Helena C. Murphy
Queen Mary University of London
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Helena C. Murphy.
Pharmacogenetics | 2000
Helena C. Murphy; Colin T. Dolphin; Azara Janmohamed; Heather C. Holmes; Helen Michelakakis; Elizabeth A. Shephard; Ronald A. Chalmers; Ian R. Phillips; Richard A. Iles
We have previously shown that primary trimethylaminuria, or fish-odour syndrome, is caused by an inherited defect in the flavin-containing monooxygenase 3 (FMO3) catalysed N-oxidation of the dietary-derived malodorous amine, trimethylamine (TMA). We now report a novel causative mutation for the disorder identified in a young girl diagnosed by proton nuclear magnetic resonance (NMR) spectroscopy of her urine. Sequence analysis of genomic DNA amplified from the patient revealed that she was homozygous for a T to C missense mutation in exon 3 of the FMO3 gene. The mutation changes an ATG triplet, encoding methionine, at codon 82 to an ACG triplet, encoding threonine. A polymerase chain reaction/restriction enzyme-based assay was devised to genotype individuals for the FMO3Thr82 allele. Wild-type and mutant FMO3, heterologously expressed in a baculovirus-insect cell system, were assayed by ultraviolet spectrophotometry and NMR spectroscopy for their ability to catalyse the N-oxidation of TMA. The latter technique has the advantage of enabling the simultaneous, direct and semi-continuous measurement of both of the products, TMA N-oxide and NADP, and of one of the reactants, NADPH. Results obtained from both techniques demonstrate that the Met82Thr mutation abolishes the catalytic activity of the enzyme and thus represents the genetic basis of the disorder in this individual. The combination of NMR spectroscopy with gene sequence and expression technology provides a powerful means of determining genotype-phenotype relationships in trimethylaminuria.
Biochemical Journal | 2001
Shamus P. Burns; Helena C. Murphy; Richard A. Iles; Robert D. Cohen
When isolated livers from starved rats are perfused with lactate at constant perfusate pH and P(co(2)), there is a marked gradient of cell pH (pH(i)) along the length of the lobular radius, with periportal cells being substantially more alkaline than perivenous cells. In the present studies, the perivenous 21% of the lobular volume was destroyed by retrograde digitonin perfusion, and antegrade perfusion restored. pH(i) was determined by (31)P-NMR. The remaining periportal cells, the site of gluconeogenesis from lactate, had a substantially higher mean pH(i) (7.42) than did the intact liver (7.23). When lactate was removed from the perfusate, mean pH(i) decreased to 7.25. The corresponding concentration of cell bicarbonate fell with a half-time of approximately 5 min. When lactate was re-introduced mean pH(i) rose to 7.34. We conclude that a major contributor to periportal alkalinity under these conditions is proton consumption during gluconeogenesis from lactate ions.
NMR in Biomedicine | 2000
Shamus P. Burns; G. Regan; Helena C. Murphy; P. Kinchesh
We demonstrate that MRI imaging at sub‐millimetre resolution can distinguish between periportal and perivenous zones of the rat liver lobule. This made it possible to measure the hepatic lobular radius in ex‐vivo perfused fixed livers using MRI. Comparisons of histomorphometric and MRI measurements of lobular radius were in good agreement, although MRI measurements were significantly smaller (P < 0.001). Male rats whose mothers were fed 40% of the protein of controls during gestation and lactation, had a significantly larger hepatic lobular radius than that of controls [449 ± 11 µm vs 373 ± 9 µm (mean ± SEM), respectively, p < 0.001, n = 12; histomorphometry data]. The proton T2 in periportal and perivenous zones was mapped both before and after antegrade or retrograde perfusion of 10 ml of digitonin (4 mg ml−1). Only the T2 of the hypointense regions increased significantly following antegrade perfusion of digitonin and conversely only that of the intense regions following retrograde perfusion. Digitonin causes permeabilization of cells in specific hepatic zones, determined by the direction of perfusion. The intense and hypointense regions of the hepatic MR images thus arise from the perivenous and periportal zones of the hepatic lobule, respectively. Copyright
Life Sciences | 2004
Irina Bogdarina; Helena C. Murphy; Shamus P. Burns; Adrian J. L. Clark
Biochemical and Biophysical Research Communications | 1997
Helena C. Murphy; Mika Ala-Korpela; John J. White; Alia Raoof; Jimmy D. Bell; Maria L. Barnard; Shamus P. Burns; Richard A. Iles
Clinical Chemistry | 2002
Adrian C. Sewell; Helena C. Murphy; Richard A. Iles
Diabetes | 2003
Helena C. Murphy; Gemma Regan; Irina Bogdarina; Adrian J. L. Clark; Richard A. Iles; Robert D. Cohen; Graham A. Hitman; Colin L. Berry; Zoe Coade; Clive J. Petry; Shamus P. Burns
Biochemistry | 2000
Helena C. Murphy; Shamus P. Burns; John J. White; Jimmy D. Bell; Richard A. Iles
Biochemical Journal | 2000
Shamus P. Burns; Helena C. Murphy; Richard A. Iles; R. A. Bailey; Robert D. Cohen
Archive | 2002
Helena C. Murphy; Richard A. Iles