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Biomedical subjects

B Doonan

Publications and source records attributed to B Doonan.

7 recordsLinked to original sources
PubMed1991

Unitary model of cell activation, growth control, cancer and other diseases: 1. Activated oxygen species and arachidonic acid modulation of solute permeabilities, internal Ca, Na and AOS levels and DNA transcription and synthesis.

A comprehensive model of cellular activation and proliferation is developed. The model has arachidonic acid (ARA) produced mainly from PLA2 on both sides of the membrane, and superoxide and other activated oxygen species (AOS) formed from O2 by electrons passing out through membrane NANPH and NADH oxidases, as the immediate stimulants of solute permeability. Both ARA and AOS interact with the various solute channel proteins especially their external thiols and disulfides, to increase influx of metabolic substrates, Na, Ca and O2. PLA2 and NADPH oxidase are turned on by growth factors at their receptors acting through tyrosine kinase phosphorylations of messenger proteins GP and ras p-21, stimulated proteases, and by Ca-calmodulin. The adenylate cyclase system has opposite, deactivating character as it increases efflux of Ca and desensitizes growth factor receptors by phosphorylation to shut down the increased solute permeability. Most cancer types are due to carcinogen binding to cell membrane channel and mitochondrial sites for increased solute influx with excessive AOS production inside the cell from mitochondria and other vesicles. High Ca, Na and AOS stimulate proliferation with extra high levels causing transformation to the autogenic, more embryonic-type cancer cell.

Animals↗
PubMed1987

Nonexclusive solute transport thru protein channels. Model of the Na,K ATPase complex and similar channels as general transport routes.

In earlier work this author put forward a model of the Na,K ATPase complex as a general transport channel. Detailed treatment was limited to anion and monovalent cation transport. Here the functional mechanisms of the Na,K ATPase and similar protein channels as transport routes for all ionic fluxes and also amino acid, sugar and other solutes are presented. Anions, monosaccharide -OH groups and amino acid carboxyls bind to common arginyls and lose hydration water. They combine with cations which bind to adjacent side chain carboxyls, forming neutral ion pairs or positively charged complexes which have minimums in size, hydration and free polar groups. The smaller size and polarity facilitate entry into the tight, structured water channel of some 8-10 A outer bore. Solute fluxes depend on membrane redox activity which maintains channel sulfhydryls in reduced state required for proper transport. ATP binding at channels contributes to transport conformation while ATP hydrolysis gives high efflux of Na+, H+ and Ca2+ as phosphate ion pairs. This cation efflux current clears cations from inner membrane sites, increases negative potential and provides Na+ and H+ about the outer combining sites, while maintaining their inward gradients. Binding of many agents widens the outer bore to give larger, less selective influx.

Animals↗
PubMed1985

Model of anion and monovalent cation transport as neutral ion pairs through lipophilic water channels of the Na,K ATPase complex.

A model of anion and monovalent cation transport through a lipophilic water channel of the Na,K ATPase complex is presented. Literature data for the Na,K ATPase cation binding sites are combined with data for the anion binding sites of Band 3 to obtain adjacent cation and anion combining sites at the inner and outer channel mouths. Cations and anions form neutral ion pairs or undissociated acids at these sites and then partition much more favorably into lipophilic channel water, passing through the channel in diffusive fashion. Cation movements in an "uphill" direction occur without an enzyme translocating moiety and its specific energetic requirement. The pertinent factors are the exclusion of unpaired cations by the tight channel and the site selectivity or pickup ratios for Na/K at each side which dominate over bulk and transmembrane concentration ratios. ATP hydrolysis provides phosphate for ion pairing.

Anions↗
PubMed1984

Model of visual focussing involving extraocular muscles and the causes of myopia and glaucoma.

The classical model of visual focus has increased curvature of the lens for accommodation and flattening of the lens for far vision, with both determined by ciliary muscle tension. This new model proposes that change in the focal length is a second modulator of acuity. This model also proposes that the extraocular muscles are the more important neuromuscular entities for both lens and focal length changes. At accommodation there would be relaxation of the recti muscles and contraction of the superior oblique muscle. This increases focal length while allowing the ciliary muscle ring to contract, releasing tension on the lens capsule. Far object focus is due to contraction of the recti muscles. These pull on the sclera, stretching the zonule fibers taut to give flattening tension of the lens capsule. The myopic eye, in addition to a highly curved lens, also has longer focal length and is misaligned in the orbit. Ageing glaucoma is hypothesized as due to: 1. excessive curvature of an ageing lens; 2. chronic contraction of the recti in compensatory effort to flatten the lens and shorten the focal length; 3. the overcontracted recti pull to excess, stretching the inner tissue and distorting the Schlemm canal and its access mesh area to inhibit efflux of aqueous fluid.

Accommodation, Ocular↗
PubMed1981

Solute asymmetric energy of transfer (channel partition) model and the cause of cancer.

A model for all solute transport is outlined in which flux rates and intracellular accumulation depend on partition barriers to the solute at the inner and outer channel openings of the intramembrane particles. Carcinogens would bind at and enlarge the outer channel opening, allowing increased influx of Na and Ca and thus triggering cellular replication.

Cell Division↗
PubMed1977

Membrane fluidity gradient model of cell transport.

A new model of cellular transport is presented, characterized by selective fluxes due to membrane fluidity gradient. This mechanism is treated in terms of the interfacial tensions at the membrane/cytoplasm and membrane/medium surfaces. A higher interior fluidity (lower interfacial tension) is maintained by cytoplasm adenosine triphosphate, which adsorbs and increases lipoprotein fluidity while it also chelates calcium and keeps it from inner membrane sites. The high medium calcium causes a stiffer membrane (higher interfacial tension) on the medium side. These two different free energy barriers at inner and outer channel mouths filter all molecules, whether ionized or nonelectrolytic. Molecules with excess of hydrophobic groups, which makes negative the free energy of transfer from the medium into the membrane, have highest influx. Intermolecular salt linkages and hydrogen-bonding are vital in making negative the free energy of transfer of amino acids and sugars. The much lower energy barrier at the cytoplasmic interface favors net efflux from the cell of the more polar ions and amphipaths. Intramembrane particles are proposed as the channel sites.

Adenosine Triphosphate↗