Inhisitory effect of acetazolamide on the activity of acetyl CoA carboxylase of mouse liver

Cao, Thanh Phoung; Rous, Simonne

doi:10.1016/0024-3205(78)90449-6

Cited by 24 publications

(7 citation statements)

References 15 publications

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“…by SCAIs reported earlier by Cao and Rous [16] and interactions that were being reported between carbonic anhydrase V and two other carboxylases. For instance, SCAIs had been observed to inhibit urea synthesis [2][3][4][17][18][19] and gluconeogenesis from pyruvate, but not glutamine [3,4,12,[19][20][21].…”

Section: Introductionsupporting

confidence: 55%

Role of hepatic carbonic anhydrase in de novo lipogenesis

Lynch

Fox

Hazen

et al. 1995

Biochemical Journal

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The role of carbonic anhydrase in de novo lipid synthesis was examined by measuring [1-14C]acetate incorporation into total lipids, fatty acids and non-saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased incorporation of 14C into total lipids. Both fatty acid and non-saponifiable lipid components of the total lipid were inhibited to approximately the same extent by 100 microM TFMS (29 +/- 0.3% and 35 +/- 0.3% of control respectively in replicate studies). However, neither drug significantly affected ATP concentrations or the transport activity of Na+/K(+)-ATPase, two measures of cell viability. To establish the site of this inhibition, water-soluble 14C-labelled metabolites from perchloric acid extracts of the radiolabelled cells were separated by ion-exchange chromatography. TFMS inhibited 14C incorporation into citrate, malate, alpha-oxoglutarate and fumarate, but had no effect on incorporation of 14C into acetoacetate. Since ATP citrate-lyase, the cytosolic enzyme that catalyses the conversion of citrate into acetyl-CoA, catalyses an early rate-limiting step in fatty acid synthesis, levels of cytosolic citrate may be rate controlling for de novo fatty acid and sterol synthesis. Indeed citrate concentrations were significantly reduced to 37 +/- 6% of control in hepatocytes incubated with 100 microM TFMS for 30 min. TFMS also inhibited the incorporation of 14C from [1-14C]pyruvate into malate, citrate and glutamate, but not into lactate. This supports the hypothesis that TFMS inhibits pyruvate carboxylation, i.e. since all of the 14C from [1-14C]pyruvate converted into citric acid cycle intermediates must come via pyruvate carboxylase (i.e. rather than pyruvate dehydrogenase). Our findings indicate a role for carbonic anhydrase in hepatic de novo lipogenesis at the level of pyruvate carboxylation.

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Section: Introductionsupporting

confidence: 55%

Role of hepatic carbonic anhydrase in de novo lipogenesis

Lynch

Fox

Hazen

et al. 1995

Biochemical Journal

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“…Inhibitors of carbonic anhydrase also inhibit fatty acid synthesis in mouse liver (Rous & Favarger, 1963) and in reptilian liver (Herbert & Coulson, 1984). Furthermore, Cao & Rous (1978) demonstrated that acetazolamide inhibited acetyl-CoA carboxylase (EC 6.4.1.2) (the regulatory step in fatty acid synthesis) in a cytosolic fraction from mouse liver, but only at concentrations of acetazolamide sufficient to inhibit the CA III isoenzyme of carbonic anhydrase. Such concentrations had no inhibitory effect on fatty acid synthetase activity.…”

Section: Discussionmentioning

confidence: 98%

Acetazolamide-insensitive carbonic anhydrase activities in liver and tonic skeletal muscle of adult male rats with streptozotocin-induced diabetes mellitus

Moynihan

Ennis

1990

Biochemical Journal

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One of the four discrete isoenzymes of carbonic anhydrase hitherto characterized, CA III, has the lowest turnover rate and the greatest resistance to inhibition by sulphonamides. Streptozotocin-induced diabetes mellitus resulted in a reduction in acetazolamide-resistant activity of carbonic anhydrase in the liver, but not in tonic skeletal muscle, of adult male rats. The hepatic activity declined with apparent first-order kinetics [calculated rate constant (k) 0.089 day-1] to a minimum of approx. 6% of control values; the reduction in activity was moderated by administration of insulin.

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“…Lipogenesis was inhibited by acetazolamide, a CA-specific inhibitor, in human adipose tissue (Bray, 1977). The administration in vivo of acetazolamide in female mice resulted in decreased fatty acid synthesis (Cao and Rous, 1978). In addition, Herbert and Coulson (1983) demonstrated that de novo fatty acid synthesis (measured by [ 14 C]acetate incorporation into total lipid) in liver of American chameleons (Anolis carolinensis) was inhibited by CA-specific inhibitors (ethoxyzolamide and acetazolamide).…”

mentioning

confidence: 99%

Biochemical and Molecular Inhibition of Plastidial Carbonic Anhydrase Reduces the Incorporation of Acetate into Lipids in Cotton Embryos and Tobacco Cell Suspensions and Leaves

Hoang

Chapman

2002

Plant Physiology

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Two cDNAs encoding functional carbonic anhydrase (CA) enzymes were recently isolated from a non-photosynthetic, cotyledon library of cotton (Gossypium hirsutum) seedlings with putative plastid-targeting sequences (GenBank accession nos. AF132854 and AF132855). Relative CA transcript abundance and enzyme activity increased 9 and 15 times, respectively, in cotton embryos during the maximum period of reserve oil accumulation. Specific sulfonamide inhibitors of CA activity significantly reduced the rate of [ 14 C]acetate incorporation into total lipids in cotton embryos in vivo, and in embryo plastids in vitro, suggesting a role for CA in plastid lipid biosynthesis. CA inhibitors did not affect acetyl-coenzyme A carboxylase activity or total storage protein synthesis. Similar results were obtained for two other plant systems: cell suspensions (and isolated plastids therefrom) of tobacco (Nicotiana tabacum), and chloroplasts isolated from leaves of transgenic CA antisensesuppressed tobacco plants (5% of wild-type CA activity). In addition, tobacco cell suspensions treated with the CA inhibitor ethoxyzolamide showed a substantial loss of CO 2 compared with controls. The rate of [ 14 C]acetate incorporation into lipid in cell suspensions was reduced by limiting external [CO 2 ] (scrubbed air), and this rate was further reduced in the presence of ethoxyzolamide. Together, these results indicate that a reduction of CA activity (biochemical or molecular inhibition) impacts the rate of plant lipid biosynthesis from acetate, perhaps by impairing the ability of CA to efficiently "trap" inorganic carbon inside plastids for utilization by acetyl-coenzyme A carboxylase and the fatty acid synthesis machinery.Carbonic anhydrase (CA, EC 4.2.1.1) is a zinccontaining metalloenzyme that catalyzes the reversible hydration of CO 2 to HCO 3 Ϫ . The widespread abundance of CA isoforms in plants, animals, and microorganisms suggest that this enzyme has many diverse roles in biological processes. CA plays a critical role in biological systems because CO 2 gas is the membrane permeable form of inorganic carbon for cells, and, in general, the uncatalyzed interconversion between HCO 3 Ϫ and CO 2 is slow when compared with the required rate in living cells (Badger and Price, 1994).In photosynthetic organisms, one generally accepted physiological role of CA is to provide sufficient levels of inorganic carbon as part of a CO 2 -concentrating mechanism for improved photosynthetic efficiency. In Chlamydomonas reinhardtii, Badger and Price (1992) suggested that chloroplastic CA plays a role in photosynthetic carbon assimilation by converting accumulated pools of HCO 3 Ϫ to CO 2 , which is the substrate for Rubisco. Moroney et al. (1985) revealed that the reduction of periplasmic CA activity by using CAspecific inhibitors significantly reduced the efficiency of external inorganic carbon utilization for photosynthesis. Like green algae, CA in cyanobacteria plays an important role in the CO 2 -concentrating mechanism and in photosynthesis (Badger an...

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Inhisitory effect of acetazolamide on the activity of acetyl CoA carboxylase of mouse liver

Cited by 24 publications

References 15 publications

Role of hepatic carbonic anhydrase in de novo lipogenesis

Role of hepatic carbonic anhydrase in de novo lipogenesis

Acetazolamide-insensitive carbonic anhydrase activities in liver and tonic skeletal muscle of adult male rats with streptozotocin-induced diabetes mellitus

Biochemical and Molecular Inhibition of Plastidial Carbonic Anhydrase Reduces the Incorporation of Acetate into Lipids in Cotton Embryos and Tobacco Cell Suspensions and Leaves

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