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Biomedical subjects

M C Goodall

Publications and source records attributed to M C Goodall.

18 recordsLinked to original sources
PubMed1977

Reconstitution of a proton pump from gastric mucosa.

Purified vesicular fractions from hog gastric mucosa have been incorporated into phosphatidyl serine bilayers. In the presence of MgATP on one side and symmetrical Na2SO4 solutions, a short circuit current (SCC) away from that side is observed increasing exponentially with time, while the corresponding open circuit potential (OCP) is maintained constant for greater than 30 min. In K2SO4 solutions the SCC time course is essentially unchanged, but the OCP falls to almost zero after 15-20 min. In Na -- K gradient there is a similar SCC away from the K-side whose exponential rate is increased by ATP added to both sides. The time course of these events depends only on the time from the formation on the black film. These results are interpreted as showing: (1) There is an ATP-driven proton pump generating a constant potential EH in series with a time dependent conductance gHocekt. (2) There is a shunting K-conductance gKocek't. (3) In the presence of ATP k' greater than k. (4) This time dependence is due to thickness changes in the bilayer. A model relates these results to those obtained with the intact vesicles.

Adenosine Triphosphatases↗
PubMed1971

The gramicidin A transmembrane channel: characteristics of head-to-head dimerized (L,D) helices.

A series of helical structures for gramicidin A, with alternating L and D residues, are characterized as to number of residues per turn, atoms in hydrogenbonded rings, and dihedral angles. Because of alternating peptide C-O directions, these helices are capable of forming head-to-head hydrogen-bonded dimers with the capacity of functioning as transmembrane channels. The dimers are characterized as to channel length, pore size, and expected ion selectivity. In a test of the proposed head-to-head association for channel formation, the malonyl dimer [N,N'-(dideformyl gramicidin A)-malonamide] was synthesized. The chemical and conformational integrity of the product was verified by nuclear magnetic resonance; in lipid bilayer studies, the dimer was found to be a potent mediator of ion conductance with the predicted concentration dependence.Thus, the results on malonyl gramicidin A prove head-to-head association in formation of the transmembrane channel, and the results are consistent with the specific geometrical configuration involved in head-to-head dimerization of pi((L,D)) helices. At this stage, the action of gramicidin A on membranes with lipid-layer thicknesses of 30 A or less can best be understood in terms of the pi((L,D)) helix with 6.3 residues per turn.

Amino Acid Sequence↗
PubMed1971

Decreased noradrenaline (norepinephrine) synthesis in familial dysautonomia.

Noradrenaline synthesis and metabolism of dopamine was evaluated in three patients with familial dysautonomia and compared with that of six normal subjects. Each patient and subject was infused with 104.8 muCi of dopamine-2-(14)C dissolved in 1000 ml of physiological saline. The urine was collected during the infusion period and at intervals thereafter. Using a specially designed flow monitor system, the various biosynthetic and metabolic products of dopamine were separated, identified, and their radioactivity measured. The results indicate that in familial dysautonomia the synthesis of noradrenaline is significantly decreased; this is reflected by a decrease in recovery of radioactive noradrenaline as well as various metabolic products of noradrenaline, i.e. 3-methoxy-4-hydroxymandelic acid (MOMA), normetadrenaline, and normetadrenaline conjugate. Concomitant with this decrease in noradrenaline synthesis, there was a shift towards dopamine metabolism as reflected by an increase in the recovery of primary and secondary dopamine metabolites; 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylacetic acid (HVA), 3-methoxytyrosine, and respective conjugates, etc. Whereas all dysautonomic patients showed the same general metabolic pattern as was expected, they varied in degree.

Adult↗
PubMed1969

Dopamine (3-hydroxytyramine) replacement and metabolism in sympathetic nerve and adrenal medullary depletions after prolonged thermal injury.

After severe thermal injury, the adrenal medulla and the sympathetic nerves can be partially or totally depleted of their adrenaline (epinephrine) and noradrenaline (norepinephrine). The purpose of this paper is to elucidate the rate at which dopamine-2-(14)C, a precursor of noradrenaline, is synthesized into noradrenaline and noradrenaline metabolic products, thereby giving some indication as to dopamine's utilization, turnover, and possible use in treating such noradrenaline-adrenaline depletions. Three burned subjects, 3 wk postburn, were infused with 104.6 muc (872 mug) of dopamine-2-(14)C for 4 hr. Urine was collected at various hourly intervals for the 1st day, and thereafter for 4 days, assayed, and compared with the metabolism of dopamine in normal subjects. Methods for separating, identifying, and counting radioactivity of the various metabolic products of dopamine are described. Normally 87.6 +/-3.1% of the total radioactivity is recovered within 24 hr after an infusion of dopamine-2-(14)C, but in the three severely burned patients, this value was increased to 93.1, 97.3, and 97.5% in 24 hr. There was a marked decrease in the percentage of radioactivity recovered as noradrenaline in all collection periods, and in contrast to normal subjects, no radioactive noradrenaline was recovered after 24 hr. Concomitantly, there was an increase in radioactivity recovered as metabolic products of noradrenaline, reflecting a compensatory shift toward noradrenaline synthesis and utilization at the expense of the dopamine metabolic products. The results indicate that in the burned patients the infused dopamine-2-(14)C was rapidly synthesized into noradrenaline and then rapidly released and metabolized. From these results it seems evident that dopamine would be a useful adjunct in the treatment of sympathico-adrenal medullary depletion in burns.

Adrenal Medulla↗