Cited by 165Mitochondrial Function and PathologyBiochemical Acid Research StudiesAdipose Tissue and Metabolism

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Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat

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McCormack, J G, Denton, R M·1980·Biochemical Journal

DOI 10.1042/bj1900095PMC PMC1162067

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Abstract

1. Increasing concentrations of both Ca2+ and Sr2+ (generated by using EGTA buffers) resulted in 4-fold increases in the initial activity of pyruvate dehydrogenase within intact uncoupled mitochondria from rat epididymal adipose tissue incubated in the presence of the ionophore A23187, ATP, Mg2+ and oligomycin. The k0.5 values (concentrations required for half-maximal effects) for Ca2+ and Sr2+ were 0.54 and 7.1 microM respectively. In extracts of the mitochondria, pyruvate dehydrogenase phosphate phosphatase activity was stimulated about 4-fold by Ca2+ and Sr2+, with k0.5 values of 1.08 and 6.4 microM respectively. 2. NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase appeared to be rate-limiting in the oxidation of threo-Ds-isocitrate and oxoglutarate by uncoupled mitochondria from brown adipose tissue of cold-adapted rats. Ca2+ (and Sr2+) diminished the Km for the oxidation of both threo-Ds-isocitrate and oxoglutarate. The kinetic constants for these oxidations were very similar to those obtained for the activities of NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase in extracts of the mitochondria. In particular, the k0.5 values for Ca2+ were all in the range 0.2–1.6 microM and Sr2+ was found to mimic Ca2+, but with k0.5 values about 10 times greater. 3. Overall, the results of this study demonstrate that the activities of pyruvate dehydrogenase, NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase may all be increased by Ca2+ and Sr2+ within intact mitochondria. In all cases the k0.5 values are close to 1 and 10 microM respectively, as found for the separated enzymes. Experiments on brown-adipose-tissue mitochondria incubated in the presence of albumin suggest that it may be possible to use the sensitivity of the dehydrogenases to Ca2+ as a means of assessing the distribution of Ca2+ across the mitochondrial inner membrane.

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Authors: McCormack, J. G., & Denton, R. M.
Affiliations: University of Bristol (GB)
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 1980-07-15
Volume: 190
Issue: 1
Pages: 95-105
ISSN: 0264-6021 (ISSN-L)
DOI: 10.1042/bj1900095
PMC: PMC1162067
OpenAlex: W130501137
Cited by: 165
References: 17
Citations by year: 2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 2 · 2013: 4 · 2012: 3
FWCI: 5.68
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: calcium ions, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, strontium, white adipose tissue, brown adipose tissue, cold adaptation, substrate Km, A23187
MeSH terms: Calcimycin, Adenosine Triphosphate, Adipose Tissue, Animals, Adipose Tissue, Brown, Calcium, Kinetics, Male, Mitochondria, Oxidoreductases, Serum Albumin, Bovine, Strontium, Rats, In Vitro Techniques

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Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat

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