The role of the enzyme in the succinate-enzyme-fumarate equilibrium

The following is an account of an investigation into the role of the enzyme in the succinate-enzyme-fumarate equilibrium. The method consisted in the comparison of the value of the free energy change in this reaction obtained from oxidation-reduction potentials, with that calculated from the entropies and other physicochemical properties of succinic acid and fumaric acid

Reversibility in Biological Oxidations

I. The molal electrode potential for the succinate-enzyme- fumarate equilibrium was determined for a series of variations of all the constituents, at 25°. The free energy and the heat of the reaction, determined electrometrically, are compared to the values calculated from known physico-chemical properties of succinic and fumaric acids. The values agree within the limits of experimental error. This, together with the lack of dependence of the free energy on the source of the enzyme, is taken to indicate that the enzyme behaves as a perfect catalyst. II. From the equilibrium constant for the reaction of fumarate and water to form 1-malate in the presence of the enzyme fumarase, the free energy of the reaction was calculated. From this value and the known physico-chemical properties of fumaric acid, the free energy of the formation of 1-malic acid was estimated. III. It was demonstrated that in the presence of toluene-treated B. coli, lactate is oxidized to pyruvate, and that furthermore, pyruvate may also be reduced to lactate. IV. It was shown that in the presence of toluene-treated B. coli electron or hydrogen transfer from one metabolite to another occurs only thru the mediation of a reversible oxidizing agent. V. The implications of these findings for the theory of biological oxidations are discussed.</p

On simultaneous measurements with rotor, wing and acoustic current meters, moored in shallow water

In two closely spaced moorings in the Kiel Bight, four different current meterstwo rotor current meters (Aanderaa and Vector averaging), an acoustic current meter (designed by Gytre), and a pendulum current meter (designed by Niskin) were moored for 22 days. The Vector averaging current meter (VACM) was used as reference instrument on one mooring with the floatation at 7 m depth. The floatation of the second mooring was at 5 m depth in the first 17 days of the experiment, but in 2.7 m depth in the last 5 days to make their mooring more effected by surface waves. The Niskin wing current meter was most effected by wave-induced mooring motion. The Gytre instrument showed the smallest surface-wave effects. The vector variances of this instrument in 7.4 m depth on the surface-wave effected mooring and those of the VACM in 10 m depth on the reference mooring were about equal

The free energy, heat, and entropy of formation of l-malic acid

In the previous communication (1), it was shown that the free energy of the bivalent fumarate ion at 25° is -144,630 calories. In the present communication the measurement of the equilibrium at 25° between fumaric acid and malic acid in the presence of fumarase is reported, and from the values obtained computations are made of the free energy and heat of formation of the bivalent l-malate ion and of the free energy and entropy of solid l-malic acid

Nitrous oxide cycling in the Arabian Sea

Depth profiles of dissolved nitrous oxide (N2O) were measured in the central and western Arabian Sea during four cruises in May and July–August 1995 and May–July 1997 as part of the German contribution to the Arabian Sea Process Study of the Joint Global Ocean Flux Study. The vertical distribution of N2O in the water column on a transect along 65°E showed a characteristic double-peak structure, indicating production of N2O associated with steep oxygen gradients at the top and bottom of the oxygen minimum zone. We propose a general scheme consisting of four ocean compartments to explain the N2O cycling as a result of nitrification and denitrification processes in the water column of the Arabian Sea. We observed a seasonal N2O accumulation at 600–800 m near the shelf break in the western Arabian Sea. We propose that, in the western Arabian Sea, N2O might also be formed during bacterial oxidation of organic matter by the reduction of IO3 − to I−, indicating that the biogeochemical cycling of N2O in the Arabian Sea during the SW monsoon might be more complex than previously thought. A compilation of sources and sinks of N2O in the Arabian Sea suggested that the N2O budget is reasonably balanced

Open-ocean convection: observations, theory and models

We review what is known about the convective process in the open ocean, in which the properties of large volumes of water are changed by intermittent, deep-reaching convection, triggered by winter storms. Observational, laboratory, and modeling studies reveal a fascinating and complex interplay of convective and geostrophic scales, the large-scale circulation of the ocean, and the prevailing meteorology. Two aspects make ocean convection interesting from a theoretical point of view. First, the timescales of the convective process in the ocean are sufficiently long that it may be modified by the Earth's rotation; second, the convective process is localized in space so that vertical buoyancy transfer by upright convection can give way to slantwise transfer by baroclinic instability. Moreover, the convective and geostrophic scales are not very disparate from one another. Detailed observations of the process in the Labrador, Greenland, and Mediterranean Seas are described, which were made possible by new observing technology. When interpreted in terms of underlying dynamics and theory and the context provided by laboratory and numerical experiments of rotating convection, great progress in our description and understanding of the processes at work is being made

Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients

Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.</p

Submicron Structures Technology and Research

Contains reports on fourteen research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)U.S. Navy - Office of Naval Research (Contract N00014-79-C-0908)National Science Foundation (Grant ECS82-05701)Semiconductor Research Corporation (Grant 83-01-033)U.S. Department of Energy (Contract DE-ACO2-82-ER-13019)Lawrence Livermore National Laboratory (Contract 2069209)National Aeronautics and Space Administration (Contract NAS5-27591)Defense Advanced Research Projects Agency (Contract N00014-79-C-0908)National Science Foundation (Grant ECS80-17705)National Aeronautics and Space Administration (Contract NGL22-009-638

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease

INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.METHODS: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aβ42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia.RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AβX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline.DISCUSSION: Our results suggest that assessing the plasma AβX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD.HIGHLIGHTS: New plasma Aβ42/Aβ40 measurement using immunoprecipitation-immunoassay Plasma Aβ42/Aβ40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.</p