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Biomedical subjects

S A Moore

Publications and source records attributed to S A Moore.

At least 145 records · Page 8Linked to original sources
PubMed1983

Synthesis and hydrolysis of ADP-arsenate by beef heart submitochondrial particles.

The kinetic parameters for inorganic phosphate and inorganic arsenate as substrates for the synthesis of ATP and ADP-arsenate, respectively, by beef heart submitochondrial particles have been determined. The Vm and Km values for arsenate and phosphate, as well as the Km values for ADP in the two reactions, are the same within experimental error of the measurements. These data are consistent with covalent bond formation not being the rate-limiting step for either ATP or ADP-arsenate synthesis. The hydrolysis of ATP and of ADP-arsenate was studied under conditions of net synthesis of ATP or ADP-arsenate. The apparent first order rate constant for ATP hydrolysis increased with submitochondrial particle concentration, indicating that hydrolysis of ATP was catalyzed by the submitochondrial particle preparation. Nonenzymic hydrolysis of ATP was negligible compared to enzymic hydrolysis. The apparent first order rate constant for ADP-arsenate hydrolysis did not vary with submitochondrial particle concentration, indicating that ADP-arsenate hydrolysis was nonenzymic. Enzymic hydrolysis of ADP-arsenate was too slow, compared with its rapid nonenzymic hydrolysis, to be detected. The first order rate constant for ADP-arsenate hydrolysis at pH 7.5, 30 degrees C, was determined to be greater than 5 min-1 and was estimated to be 70 min-1. These data confirm previous suggestions that arsenate "uncouples" oxidative phosphorylation by a mechanism involving synthesis of ADP-arsenate, followed by its rapid nonenzymic hydrolysis.

Adenosine Diphosphate↗
PubMed1983

Degenerative neuropathy in insulin-treated diabetic rats.

Peripheral neuropathic alterations associated with diabetes and its treatment with insulin were studied in alloxan-induced diabetic rats. Treatment regimens included daily injections of Protamine Zinc Insulin (PZ), daily injections of Ultralente Insulin and subcutaneously implanted osmotic minipump delivered insulin. Non-diabetic and untreated diabetic groups served as controls. Two separate but similar studies were run, one lasting 4 weeks and the other 8 weeks. Conduction velocities performed on both sensory and motor nerves revealed no statistically significant differences among groups. Anatomical analysis of teased fibers from tibial nerves showed a significant number of fibers with ovoids, consistent with Wallerian-type axonal degeneration, only in the treated diabetic groups. Degeneration was especially severe in the PZI-treated group. Metabolic studies were performed using incorporation of radioactive isotopes ([3H]fucose, [14C]leucine) into myelin proteins of sciatic nerves. The ratio of [3H]fucose/[14C]leucine for the PZI-treated group was significantly decreased when compared to the control groups in both the 4 and 8 week study whereas the minipump-treated group showed no statistically significant difference from the control group in either study. Similar decreases in this ratio have been seen in conditions of peripheral nerve degeneration. It is concluded that daily injections of PZI insulin result in significant nerve degeneration in the alloxan diabetic rat, while continuous levels of insulin delivered by osmotic minipumps result in less degeneration.

Animals↗
PubMed1983

Shock-elicited aggression as a function of acute and chronic ethanol challenges.

In a test of competing hypotheses regarding the effects of alcohol on shock-elicited aggression, animals maintained on a food restricted regimen were administered either chronic or acute ethanol challenges. Chronic Ss showed a significantly higher rate of target-directed aggression and spent significantly more time in aggressive activity than did acute or saline control animals. Results support the proposed interactive effect of food restriction and extended periods of alcohol intake leading to increased aggression.

Aggression↗
PubMed1983

Evaluation of ELISA for detecting in vivo chemical immunomodulation.

Immunotoxicology is a relatively new field of investigation and is becoming recognized and used by toxicologists involved in drug and chemical testing. The purpose of this study was to evaluate the enzyme-linked immunosorbent assay (ELISA) as a means of quantitating humoral immune responses in rats exposed to immunomodulating chemicals. The ELISA proved to be highly sensitive and quantitative, simple to perform, and reliable. The assay is also economically feasible and automated so that large numbers of samples can be analyzed at one time. The antigen used in the study was bovine serum albumin, and the immunosuppressive chemicals used to validate the system were lead, polychlorinated biphenyl, cyclophosphamide, and dexamethasone. Practical application of the procedure to immunotoxicology testing is discussed.

Animals↗
PubMed1983

Uptake of adenosine by cultured cerebral vascular smooth muscle cells.

Adenosine uptake by cerebral smooth muscle cells is a carrier-mediated process. The Km value for adenosine uptake is 10.0 microM and the Vmax is 0.95 nmol/min-mg cell protein. This uptake system is inhibited by the adenosine analog 2-chloroadenosine at low adenosine concentrations. These results prove the existence of a nucleoside transport system associated with cerebral smooth muscle.

Adenosine↗
PubMed1983

Nutrition teaching for family practice residents.

A nutrition curriculum based on principles of adult education has been developed and implemented. Through use of joint counseling as the main educational process, patient education remains the resident's responsibility with the faculty dietitian acting as consultant. At any point the resident has the opportunity to apply nutrition knowledge and to give independent nutritional counseling. Videotapes of independent counseling sessions allow self-evaluation and also permit assessment of each resident's nutrition teaching competencies. Pre-testing of each resident entering the program, followed by post-testing one month prior to graduation, permits curricular evaluation.

Adult↗
PubMed1982

Reactions of acyl phosphates with carboxylate and thiol anions. Model reactions for CoA transferase involving anhydride formation.

Succinyl phosphate reacts rapidly with the thiol N-acetyl-beta-mercaptoethylamine (a CoA analog) to form the succinate thiol ester. This is a chemical model for the enzymic reaction of CoA transferase. It is demonstrated that: 1) the chemical reaction is stepwise, proceeding through the formation of a succinic anhydride intermediate. The rate-determining step at pH 6.6 is anhydride formation. 2) The apparent equilibrium constant for anhydride formation from succinyl phosphate is increased 6000-fold in going from pH 6.6 to 4.4. Formation of the reactive anhydride intermediate is so favorable at pH 4.4 that it accumulates in the reaction solution. 3) The rate constant for anhydride formation is accelerated 60-fold in going from pH 6.6 to 4.4 due to protonation of the phosphate moiety of succinyl phosphate, which enhances its leaving ability. 4) Anhydride formation through intramolecular reaction of the --COO- group of succinyl phosphate is accelerated greater than or equal to 10(5)-fold compared to the intermolecular reaction of 1 M acetate and acetyl phosphate. Thus, in the chemical reaction, anhydride formation can be made rapid and favorable by: 1) making the reacting groups intramolecular; and 2) catalyzing the expulsion of the leaving group. These are modes of rate acceleration that can occur in enzymic reactions. This model study provides support for a mechanism that proceeds through an anhydride intermediate in the enzymic reaction catalyzed by CoA transferase.

Acyltransferases↗
PubMed1982

Model reactions for CoA transferase involving thiol transfer. Anhydride formation from thiol esters and carboxylic acids.

Rate and equilibrium constants were determined for anhydride formation from the thiol esters p-nitrophenyl thiosuccinate (PTS) and N-acetyl-S-succinyl-beta-mercaptoethylamine, and from p-nitrophenyl thioacetate in the presence of substituted acetates. These thiol esters undergo thiol transfer reactions through rate-determining anhydride formation that are models for the enzymic reaction catalyzed by CoA transferase. The same value of beta nuc approximately equal to 1.0 for the nucleophilic reactions of substituted acetates with p-nitrophenyl thioacetate and with enzyme-CoA supports the anhydride mechanism for the enzymic reactions. The bimolecular reaction of succinyl-CoA with enzyme is 10(13) times faster than the nonenzymic reaction of acetyl-CoA with acetate; the intramolecular reaction of bound substrate is accelerated by a factor of kcat/kN - 10(11) M. The nonenzymic intramolecular reaction of PTS is faster than the nucleophilic reaction of acetate with acetyl-CoA by a similar factor of 4.5 X 10(10) M, of which 6 X 10(5) M is caused by intramolecularity and 7 X 10(4) by the increased chemical reactivity of PTS compared to acetyl-CoA. The enzyme may utilize binding energy to increase the reaction rate by making the reaction intramolecular (decreasing the requirement for loss of entropy) and by destabilizing the bound substrate relative to the transition state in an analogous manner. An identical rate increase of 6 X 10(5) M from intramolecularity was observed for the reaction of N-acetyl-S-succinyl-beta-mercaptoethylamine compared with the corresponding acetate. The rate increase in the intramolecular reaction of PTS reflects more favorable values of T delta S identical = 5.0 +/- 1.4 kcal mol-1 and -delta H identical to = 2.9 +/- 1.3 kcal mol-1 compared with the bimolecular reaction.

Acyltransferases↗
PubMed1982

Formation of active site thiol esters of CoA transferase and the dependence of catalysis on specific binding interactions.

The enzyme-CoA intermediate of succinyl-CoA:3-ketoacid coenzyme A transferase reacts with methyl mercaptopropionate, a short chain analog of coenzyme A, to release coenzyme A and give a new thiol ester at the active site, enzyme-SR (E-SR). The reaction is reversible, with Keq = 2.4 X 10(-4). Other thiols react similarly, acetyl-CoA. On the other hand, the value of kcat/km for the reaction of succinyl-SR with the enzyme to form E-SR is smaller than that for the reaction of succinyl-CoA to form enzyme-CoA by a factor of 3 X 10(12). Thus, interactions of the enzyme with the nonreacting portions of coenzyme A are responsible for a rate increase of 3 X 10(12) compared with the short chain analog. This increase is close to the total rate acceleration of 5 X 10(13) that is brought about by the enzyme. The rate increase is interpreted as representing 17 kcal mol-1 of intrinsic is interpreted as representing 17 kcal mol-1 of intrinsic binding energy of coenzyme A that is utilized to stabilize the transition state of the reaction; the observed binding of coenzyme A to the enzyme is relatively weak. The thiol ester group of enzyme-CoA is activated for reaction with the nonspecific reagents water, borohydride anion, and thiol anions by approximately 10(2)-10(3) compared with E-SR and thiol esters of acetate. The formation of E-SR at equilibrium is unfavorable by 5.7 kcal mol-2 compared with thiol esters of acetate, in spite of its normal chemical reactivity. This is consistent with a thermodynamically unfavorable conformation change upon thiol ester formation. The observed more favorable formation of enzyme-CoA compared to E-SR by 4.9 kcal mol-1 can be accounted for by utilization of the binding energy of coenzyme A to overcome the unfavorable Gibbs energy of this conformation change, for which there is independent evidence. The reaction of succinate with E-SR is 10(5) faster than with a thiol ester of acetate. This rate increase represents utilization of the binding energy of the specific substrate succinate for catalysis; however, no binding of succinate to E-SR was observed. A rate acceleration of 8 X 10(5) was observed for the nonphysiological reaction of coenzyme A with E-SR to give enzyme-CoA compared to the analogous nonenzymic reaction. This represents utilization of the binding energy of coenzyme A, in large part to overcome the entropy barrier for reaction. The combined effects of several modest contributions, especially the entropy loss of bound substrates, appear sufficient to account for most of the observed rate increase of the enzymic reaction without invoking ordinary mechanisms of chemical catalysis.

Acyl Coenzyme A↗
PubMed1982

Excretion of urinary volatile metabolites in response to alloxan induced diabetes of short duration in rats.

Alterations in urine volatile metabolites due to the induction of alloxan diabetes in the rat were examined by capillary gas chromatography and gas chromatography--mass spectrometry for the five days immediately following the onset of chronic hyperglycemia. Elevations of a number of metabolites were observed including several short chain ketones, acetophenone, 2-acetylfuran and indole. The value of urine volatile metabolic profiles as characteristic indicators of the diabetic condition is demonstrated through profiles obtained from a diabetic animal which spontaneously reverted to normal.

Animals↗
PubMed1982

Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins (l).

High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.

Animals↗
PubMed1982

Ultrastructural axonal pathology in experimentally diabetic and aging control rats.

Electron microscopic examination of tibial nerves from streptozotocin-diabetic, alloxan-diabetic and age-matched control rats was undertaken at two weeks and two, four, eight, and twelve months following the induction of diabetes. Many myelinated axons of both diabetic and control rats contained glycogen-like granules, axon-Schwann cell networks and fingerlike intrusions of myelin. These axonal changes were observed more frequently with advancing age and duration of diabetes, suggesting that they are related to aging or repeated injury. A larger proportion of diabetic axons than control axons were affected at early time periods, but by eight and twelve months the control axons were as frequently (or more frequently) involved as diabetic axons. Thus, experimental diabetes may confer upon peripheral myelinated axons an increased susceptability to aging or repeated injury. Specific morphologic abnormalities in peripheral myelinated axons associated uniquely with streptozotocin or alloxan diabetes in the rat were not noted.

Aging↗
PubMed1982

Conditioning and retention of defensive burying as a function of the injection of a central cholinergic stimulant.

Two groups of rats received defensive-burying testing under the effects of saline or physostigmine injection. Saline-injected animals buried more during the first (drug-state) session than did the physostigmine-injected animals. Twenty-four hours later all Ss received a retention test under the nondrug condition. Ss originally tested under the physostigmine state buried more than the saline-injected animals did.

Animals↗
PubMed1981

Rabies serum neutralizing antibody in mongooses from Grenada.

During a four-year study on Grenada, 4,754 mongooses were examined, of which 100 (2.1%) were rabid. Of 1,675 mongooses tested for rabies serum neutralizing (SN) antibody, 498 (30%) were positive. During these four years (1971-74) the antibody prevalence rate increased from 20.8% to 43.2%, whereas the number of rabid mongooses decreased from 3.5% to 0.6%. Naturally acquired antibody was monitored in 20 captive mongooses for up to 35 months, and it was still circulating in 18 when monitoring ceased. The highest titre recorded was 1:1,400, and the rate of fall was greatest in mongooses with high initial titres. High titres of naturally acquired antibody suggest recent rabies activity. 14 mongooses vaccinated parenterally with 1.0 ml of attenuated ERA vaccine showed substantial increases in antibody titres; most had titres greater than 1:1,000 one month later and maintained a high titre for several months. The highest recorded was 1:34,800. The virus titres of brain material from rabid mongooses ranged from 10(1.8) to 10(4.3) and, in some cases, were only slightly lower than those of salivary gland tissue (range, 10(1) to 10(5.6).

Animals↗
PubMed1981

The effect of diabetes on leucine and fucose incorporation into PNS myelin proteins.

Peripheral neuropathy is a common complication associated with diabetes mellitus. Segmental demyelination and other pathological changes frequently accompany loss of sensory amd motor nerve function. Morphological changes seen in diabetic nerve myelin may be a result of altered Schwann cell metabolism under hyperglycemic conditions. Using both alloxan and streptozotocin - induced diabetic rats of 2, 4 and 8 months duration of diabetes, metabolic changes in isolated sciatic nerve myelin were assessed using a double-label in vitro incubation system. Incorporation of 3H-fucose and 1-14C-leucine into myelin was determined per microgram protein. Specific activities of incorporated protein precursors were compared as a ratio of fucose to leucine. Using the Newman-Kuels test for multiple comparisons, statistically significant increases were found in the incorporation ratios of diabetic rats at 2 and 4 months of diabetes when tested against age-matched controls.

Animals↗