Binding of ADP to rat liver cytosolic proteins and its influence on the ratio of free ATP/free ADP

Mörikofer‐Zwez, Stéphanie; Walter, Paul

doi:10.1042/bj2590117

Cited by 30 publications

(18 citation statements)

References 37 publications

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“…A shift in the concentration of ADP required for optimal activity suggests that the HMW cytosolic fraction is capable of removing some of the ADP from having access to the iron, possibly by binding the nucleotides. Binding of ADP to cytosolic proteins has been observed with a cytosolic extract from rat liver (Morikofer-Zwez and Walter 1989). Where large concentrations of nucleotides exist as they do in fish muscle, 8.5 pmol/g (Jiang et al 1987), the HMW cytosol fraction may, therefore, serve to activate lipid peroxidation.…”

Section: Discussionmentioning

confidence: 98%

Effect of Cytosol on Lipid Peroxidation in Flounder Sarcoplasmic Reticulum

Erickson

Hultin

Borhan

1990

J Food Biochemistry

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Studies were carried out to determine the effects of cytosol on sarcoplasmic reticulum lipid peroxidation. Upon addition of unfractionated cytosol to the lipid peroxidation system, inhibition was observed. Fractionation revealed that both the low molecular weight (LMW) cytosol (<10,000 MW) and high molecular weight (HMW) cytosol (>6,000–8,000 MW) fractions inhibited lipid peroxidation. It is suggested that either inorganic phosphate compounds or nucleotides may be responsible for the LMW cytosol's inhibitory characteristics. Addition of the HMW cytosol fraction to the system necessitated the presence of additional adenosine 5′‐diphosphate (ADP) for optimal activity. ADP bound to the HMW cytosol fraction may be incapable of chelating the iron and preventing its precipitation as the ferric hydroxide.

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Section: Discussionmentioning

confidence: 98%

Effect of Cytosol on Lipid Peroxidation in Flounder Sarcoplasmic Reticulum

Erickson

Hultin

Borhan

1990

J Food Biochemistry

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“…due to compartmentalization. Furthermore, at least 50% of cytosolic ADP is protein‐bound [34]. Thus, whether IRP‐1 experiences subsaturating cytosolic ATP concentrations in the cell remains an open question.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of an iron‐responsive element/iron regulatory protein‐1 complex by ATP binding and hydrolysis

Popovic

Templeton

2007

The FEBS Journal

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Mechanisms of post-transcriptional regulation of gene expression include control of initiation of translation and regulation of mRNA degradation. Among the best-studied models for these processes is regulation of proteins involved in iron homeostasis. These control mechanisms involve functional iron-responsive elements (IREs) in the 5¢-UTRs or 3¢-UTRs of mRNAs that interact with iron regulatory proteins (IRPs), depending upon the amount of iron present in the cell. Two IRPs have been identified: IRP-1, which contains a 4Fe)4S iron-sulfur cluster [1], and IRP-2, which does not [2,3]. IRP-1 has 30% amino acid identity to mitochondrial aconitase [4], a 4Fe)4S enzyme involved in the tricarboxylic acid cycle. IRP-1 is generally believed to interconvert between an enzymatically inactive IRE-binding state and a nonbinding form with aconitase activity, the latter requiring an intact 4Fe-4S cluster. Thus, the simple model for iron sensing by IRP-1 involves direct association of iron with the ironsulfur center to form a complete 4Fe)4S cluster.A linkage between cellular iron levels and energy metabolism is suggested by the influence of agents that Iron regulatory protein-1 binding to the iron-responsive element of mRNA is sensitive to iron, oxidative stress, NO, and hypoxia. Each of these agents changes the level of intracellular ATP, suggesting a link between iron levels and cellular energy metabolism. Furthermore, restoration of iron regulatory protein-1 aconitase activity after NO removal has been shown to require mitochondrial ATP. We demonstrate here that the iron-responsive element-binding activity of iron regulatory protein is ATP-dependent in HepG2 cells. Iron cannot decrease iron regulatory protein binding activity in cell extracts if they are simultaneously treated with an uncoupler of oxidative phosphorylation. Physiologic concentrations of ATP inhibit ironresponsive element ⁄ iron regulatory protein binding in cell extracts and binding of iron-responsive element to recombinant iron regulatory protein-1. ADP has the same effect, in contrast to the nonhydrolyzable analog adenosine 5¢-(b,c-imido)triphosphate, indicating that in order to inhibit iron regulatory protein-1 binding activity, ATP must be hydrolyzed. Abbreviations AMP-PNP, adenosine 5¢-(b,c-imido)triphosphate; ATP-cS, adenosine 5¢-O-(3-thiotriphosphate); CCCP, carbonyl cyanide m-chlorophenylhydrazone; EMSA, electrophoretic mobility shift assay; IRE, iron-responsive element; IRP, iron regulatory protein.

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“…At high ADP levels the effects of G3139 are quite small because the lower MOM permeability is compensated by the higher [ADP]. Inside the cell, more than half the ADP is bound to proteins (3,4,28). The free [ADP] from various cell types is not directly known but has been estimated to be 6 -90 M (3,36,45).…”

Section: Discussionmentioning

confidence: 99%