ISSN:
1573-6881
Keywords:
Brown adipose tissue mitochondria
;
uncoupling protein
;
regulation of thermogenesis
;
modulators of purine nucleotide inhibition
;
magnesium
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
Notes:
Abstract Modulators of purine nucleotide (PN) inhibition of H+ and Cl− transport mediated by the uncoupling protein (UP) of brown adipose tissue (BAT) mitochondria were studied: Alkalinization strongly diminishes GDP inhibition of H+ transport (Δ log IC50=−ΔpHout), while more intensive inhibition of Cl− transport is only slightly altered. Higher Δω decreases GDP inhibition of H+ transport. Mg2+, but not palmitoyl-CoA, decreases PN inhibitory ability. Simulations of conditions similar to those found in BAT cells in the resting state and in the thermogenic state showed that three factors act in concert: pH, Mg2+, and free fatty acids (FFA): (a) with endogenous FFA present and 2 mM ATP and 0.5 mM AMP (pH 7.1), H+ transport was inhibited by 95% in the absence of Mg2+, while by 60% with Mg2+; (b) 0.5 mM ATP and 1 mM AMP, H+ transport was inhibited by 40% without Mg2+ and by 30% with Mg2+. State b thus represents a model thermogenic state, while state a represents a resting state. However, the latter statein vivo must be accomplished either by combustion or FFA or by elimination of Mg2+ to attain a total inhibition of H+ transport (cf. a). The model of UP possessing two independent channels, an H+ channel and a Cl− channel, controlled from a single PN-binding site is supported by independent kinetics by different pH dependence of H+ and Cl− transport, and by a lower sensitivity of H+ transport to PN inhibition.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00768922
Permalink
