Significance of cation transport in control of energy metabolism and thermogenesis.

Clausen, Torben; Hardeveld, C. van; Everts, M. E.

doi:10.1152/physrev.1991.71.3.733

Cited by 216 publications

(182 citation statements)

References 0 publications

Supporting

Mentioning

176

Contrasting

Order By: Relevance

“…The Na+/K+-ATPase is the major ATPase in brain and kidney and is a significant ATP user in other cells (Clausen et al, 1991). The isolated Na+/K+-ATPase is relatively insensitive to ATP, but the apparent sensitivity measured in cells is higher, with activity roughly proportional to ATP concentration in rat kidney proximal tubules (Soltoff& Mandel, 1984;Tessitore et al, 1986), and cultured HeLa cells (Ikehara et al, 1984), and a greater sensitivity in brain synaptosomes (Dagani & Erecinska, 1987;Erecinska & Dagani, 1990 (Soltoff, 1986).…”

Section: Application Of Metabolic Control Theorymentioning

confidence: 99%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

View full text Add to dashboard Cite

We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Application Of Metabolic Control Theorymentioning

confidence: 99%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

View full text Add to dashboard Cite

show abstract

“…Thyroid hormone induces an increase in cardiac contractility and frequency, resulting in a greater cardiac output (Polikar et al 1993, Toft & Boon 2000, Klein & Ojamaa 2001, and a proportional change in energy turnover (Clausen et al 1991). Thyroid hormone also induces relaxation of vascular smooth muscle (Ojamaa et al 1996), and it is very effective in reducing serum cholesterol (Staels et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Verhoeven¹,

Putten²,

Hennemann³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

Cellular and nuclear uptake of [125 I]tri-iodothyronine (T 3 ) and [125 I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T 3 uptake was measured. Cells (5-10 10 5 per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 C in the same medium, 0·5% BSA and [125 I]T 3 (100 pM), or [ 125 I]Triac (240 pM). Expressed as % dose, T 3 uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0·001) greater than T 3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [ 125

show abstract

“…It is this leak process that is depressed in hypothyroid mitochondria and stimulated in hyperthyroid mitochondria [7, 14, 151. In isolated hepatocytes, where respiration is intermediate between state 4 and state 3, control over respiration lies mostly in the reactions that form and use ATP, but there is also significant control by the mitochondrial proton leak [16]. The thyroid hormone status of the donor animals affects both the proton permeability of the mitochondrial membrane [I71 and the turnover by the plasma membrane Na+/K+ ATPase of the ATP generated by oxidative phosphorylation [3,18]. These effects each appear to account for a part of the observed differences in hepatocyte respiration rate between cells from euthyroid and hypothyroid or euthyroid and hyperthyroid animals respectively.…”

mentioning

confidence: 99%

The mechanism of the increase in mitochondrial proton permeability induced by thyroid hormones

Brand

Steverding

Kadenbach

et al. 1992

European Journal of Biochemistry

View full text Add to dashboard Cite

Three possible mechanisms by which different levels of thyroid hormones in rats might cause the observed sevenfold change in the apparent proton permeability of the inner membrane of isolated liver mitochondria were investigated. (a) Cytochrome c oxidase was isolated from the livers of hypothyroid, euthyroid and hyperthyroid rats and incorporated into liposomes made with soya phospholipids. There was no difference between the proton current/voltage curves of the three types of vesicles. The hormonal effects, therefore, were not an inherent property of the enzymes, and were not due to different coupling of electron flow through the enzyme to proton transport. (b) The surface area of the mitochondrial inner membrane was shown by three different assays to be greater by a factor of between two and three in mitochondria from hyperthyroid animals than in mitochondria from hypothyroid animals; euthyroid controls were intermediate. This difference in surface area of the inner membrane explains less than half of the difference in apparent proton permeability. (c) The proton permeability of liposomes prepared from phospholipids extracted from mitochondrial inner membranes of hyperthyroid rats was three times greater than the proton permeability of those from hypothyroid rats; euthyroid controls were intermediate. This suggests, first, that the proton permeability of the phospholipid bilayer is an important component of the proton permeability in intact mitochondria and, second, thyroid hormone-induced changes in the bilayer are a major part of the mechanism of increased proton permeability. Such changes may be due to the known differences in fatty acid composition of mitochondrial phospholipids in different thyroid states. Thus we have identified two mechanisms by which thyroid hormone levels in rats change proton flux/mass protein in isolated liver mitochondria: a change in the area of the inner membranelmass protein and a change in the intrinsic permeability of the phospholipid bilayer.Mitochondria isolated from the livers of hypothyroid animals ('hypothyroid mitochondria') have respiration rates that are lower than euthyroid controls, and mitochondria isolated from the livers of hyperthyroid animals ('hyperthyroid mitochondria') have respiration rates that are higher than euthyroid controls [1,2]. These changes in respiration rate are also seen in isolated hepatocytes [3], showing that they are not artefacts of isolation of the subcellular organelles. They are thought to be an important part of the changes in metabolic rate and heat production controlled by thyroid hormones There are two separate effects of thyroid hormone levels on respiration rate of isolated mitochondria: one is important in state-3 respiration, in which ADP is rapidly phosphorylated to ATP; the other is dominant in conditions in which there is little or no ATP synthesis [7, 81. The main effect on state-3 respiration is a stimulation by thyroid hormones of the reactions involved in the phosphorylation of ADP and the export of ATP; probably at the ad...

show abstract

Significance of cation transport in control of energy metabolism and thermogenesis.

Cited by 216 publications

References 0 publications

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

The mechanism of the increase in mitochondrial proton permeability induced by thyroid hormones

Contact Info

Product

Resources

About