On the mechanism of uncoupler‐dependent inhibition of acyl‐carnitine oxidation by rat liver mitochondria

Osmundsen, Harald; Bremer, Jon

doi:10.1016/0014-5793(76)80691-6

Cited by 24 publications

(6 citation statements)

References 13 publications

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“…The change in flux was greatest over the range 200-300 mosm. Such results are in agreement with those obtained radiochemically with [ l-'4C]hexadecanoyl-carnitine (Osmundsen and Bremer, 1976), by the rates of ketogenesis (Otto and Ontko, 1982), and polarographically with hexadecanoyl-carnitine by Halestrap and Dunlop (1986).…”

Section: Nad' and Nadh Concentrations During A Pulse Of P-oxidationsupporting

confidence: 90%

“…This steady 30% reduction and the subsequent turnover of the NAD'NADH pool via the activity of complex I is probably important for the control of P-oxidation under these conditions. (Osmundsen and Bremer, 1976), by the rates of ketogenesis (Otto and Ontko, 1982), and polarographically with hexadecanoyl-carnitine by Halestrap and Dunlop (1986).…”

Section: Nad' and Nadh Concentrations During A Pulse Of P-oxidationmentioning

confidence: 99%

“…There is however a more marked effect of osmolality on p-oxidation flux (Osmundsen and Bremer, 1976;Otto and Ontko, 1982;Halestrap and Dunlop, 1986) and a locus between ETF and the coenzyme Q pool has been proposed as the site of this control (Halestrap and Dunlop, 1986). Such control may be important physiologically, for example in the hormonal control of Boxidation by glucagon (Halestrap, 1989;Tosh et al, 1988).…”

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confidence: 99%

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Redox control of β‐oxidation in rat liver mitochondria

Eaton

Turnbull

Bartlett

1994

European Journal of Biochemistry

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Coupled rat liver mitochondria were incubated with [U-i4C]hexadecanoate and carnitine which resulted in the formation of acyl-, 2-enoyl-and 3-hydroxyacyl-CoA and carnitine esters. The production of 2-enoyl-CoA and 3-hydroxyacyl-CoA esters was associated with a significant lowering of the NAD'NADH ratio, in contrast to rat muscle mitochondria [Eaton, S., Bhuiyan, A. K. M. J., Kler, R. S., Turnbull, D. M. & Bartlett, K. (1993) Biochem. J. 289, 161-1721, suggesting that control by the respiratory chain is important under normal conditions. When NAD'NADH ratios were held low by succinate-induced reverse electron flow, 3-enoyl-CoA esters were also detected, probably formed by the action of 3,2-enoyl-CoA isomerase. Measurement of the flux of P-oxidation at different osmolalities showed that flux was strongly dependent on osmolality changes in the physiological range. Measurement of the CoA and carnitine esters resulting from incubations made at different osmolalities showed that there was an increase in the amounts of the saturated acyl-CoA esters with respect to 2-enoyl-CoA and 3-hydroxyacyl-CoA esters, consistent with control by the electron-transfer flavoprotein-ubiquinone segment [Halestrap, A. P. & Dunlop, J. L. (1986) Biochem. J. 239, 559-5651. This however could not be the only factor operating as indicated by the continued presence of 2-enoyl-CoA and 3-hydroxyacyl-CoA esters at high osmolalities.Mitochondria1 P-oxidation is linked to the respiratory chain at two stages ; the 3-hydroxyacyl-CoA dehydrogenases to complex I via NAD'DJADH and the acyl-CoA dehydrogenases to ubiquinone via electron-transfer flavoprotein (ETF) and its oxidoreductase (ETF: QO). Inhibition of respiratory-chain activity at the level of complex I leads to diminished P-oxidation flux and the accumulation of 3-hydroxyacyl-CoA and 2-enoyl-CoA and carnitine esters (Bremer and

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Section: Nad' and Nadh Concentrations During A Pulse Of P-oxidationsupporting

confidence: 90%

Section: Nad' and Nadh Concentrations During A Pulse Of P-oxidationmentioning

confidence: 99%

mentioning

confidence: 99%

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Redox control of β‐oxidation in rat liver mitochondria

Eaton

Turnbull

Bartlett

1994

European Journal of Biochemistry

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“…Some experimental evidence for the latter possibility was provided in the present study by the demonstration that increased osmolality inhibits hepatic 2-deoxyglucose phosphorylation and both the basal and glucagon-induced glucose release. Similarly, experiments performed by Osmundsen and Bremer showed that hyperosmolality inhibited the mitochondria1 enzyme system catalysing fatty acid oxidation in rat liver [23]. Since basal glucose transport, as measured by 3-0-methylglucose in-and efflux remained unchanged by increases of medium osmolality in the present study, it is unlikely that alterations of cell membrane structure influence the membranebound hepatic glucose transporter protein.…”

Section: Discussionsupporting

confidence: 81%

Effect of hyperosmolality on basal and hormone‐stimulated hepatic glucose metabolism in vitro

Komjati

Kastner

Waldhäusl

et al. 1989

Eur J Clin Investigation

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To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methylglucose and uptake of 2-deoxyglucose at 400 vs. 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P less than 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.

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“…These effects of Ca2+ were accompanied by a conversion of the mitochondria from the condensed to the orthodox conformation [2,3]. Others have shown that the oxidation of palmitoyl-(-)-carnitine directly correlates (a) with increased swelling in rat liver mitochondria, as measured by a decrease in absorbance [4], and (b) with an increased sucrose-impermeable space in mitochondria from hamster brown-adipose tissue [5]. The purpose of this study therefore was to investigate whether the rate of fatty acid oxidation and the energy state of the mitochondria could be elevated, similar to that observed with CaZ+, by expansion of the matrix volume.…”

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confidence: 99%

Structure‐Function Relations between Fatty Acid Oxidation and the Mitochondrial Inner‐Membrane — Matrix Region

Otto

Ontko

1982

European Journal of Biochemistry

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Decreasing the osmolarity of the incubation media for rat liver mitochondria, by lowering the KCl or sucrose content, greatly increased the oxidation of palmitate, palmitoyl-CoA, palmitoyl-(-)-carnitine, octanoate and butyrate, but only slightly affected the oxidation of succinate, glutamate plus malate, and 3-hydroxybutyrate. Kinetic studies indicated that the increased rate of fatty acid oxidation commenced at the onset of incubation in the hypotonic media and remained relatively constant. This was accompanied by an increase in the 3-hydroxybutyrate: acetoacetate ratio, a higher rate of oxygen consumption, an increase in the extramitochondrial adenine-nucleotide phosphorylation-state ratio, and a greater state of reduction of the respiratory chain cytochromes b, c, and oxidase. Incubation of mitochondria in the hypotonic media caused a rapid decrease in the intermembrane and intracrystal spaces and concurrent expansion of the matrix, without changing the volume of the mitochondria. These observations indicate that expansion of the inner-membrane-matrix compartment of mitochondria in vitro specifically activates fatty acid oxidation at the site of beta-oxidation or at the site of its interaction with the respiratory chain, with a consequent increase in the states of reduction and phosphorylation of the mitochondria. Evidence is also presented which suggests that the activation of mitochondrial fatty acid oxidation by Ca2+ is initiated by a Ca2+-induced alteration of the structure or volume of the inner-membrane-matrix region.

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On the mechanism of uncoupler‐dependent inhibition of acyl‐carnitine oxidation by rat liver mitochondria

Cited by 24 publications

References 13 publications

Redox control of β‐oxidation in rat liver mitochondria

Redox control of β‐oxidation in rat liver mitochondria

Effect of hyperosmolality on basal and hormone‐stimulated hepatic glucose metabolism in vitro

Structure‐Function Relations between Fatty Acid Oxidation and the Mitochondrial Inner‐Membrane — Matrix Region

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