Posttranslational Modifications of Enzymes

Dreyfus, Jean‐Claude; Kahn, Axel; Schapira, F

doi:10.1016/b978-0-12-152814-0.50010-1

Cited by 82 publications

(33 citation statements)

References 149 publications

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“…We may suggest that this is due to post-translational alteration of protein kinase in mature and old erythrocytes which are long-life, anucleated cells devoid of protein renewal. Such postsynthetic functional alterations of red cell enzymes with aging was recently reviewed by us [25]. It should be noted that in fresh liver extract we found practically no pyruvate kinase phosphorylation in the absence of cyclic nucleotides (not shown).…”

Section: Discussionmentioning

confidence: 78%

Phosphorylation of Human Erythrocyte Pyruvate Kinase by Soluble Cyclic‐AMP‐Dependend Protein Kinases

Marie

Buc

Simon

et al. 1980

European Journal of Biochemistry

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Human red cell contain soluble adenosine-3', 5'-phosphate-dependent protein kinases, which are able to phosphorylate the L subunits of erythrocyte pyruvate kinase. Efficiency and maximum level of phosphorylation are very comparable in human liver and red cells. Phosphorylation of red cell pyruvate kinase results in the same kinetic modifications as for liver enzyme, namely a shift towards a 'T' allosteric state characterized by a decreased affinity for phosphoenolpyruvate and increased inhibition by the allosteric inhibitors ATP and alanine. In the course of red cell aging a small amount of partially proteolysed pyruvate kinase, devoid of the phosphorylatable site, appears; it resembles the subtilisin-treated L b enzyme and accounts for less than 20% of total pyruvate kinase subunits.Endogenous phosphorylation of pyruvate kinase from erythrocytes incubated in the presence of cyclic nucleotides produces the same kinetic modifications as phosphorylation in partially purified extract; this, however, does not change glucose consumption, lactate production and glycolytic intermediate concentrations of the incubated cells.Regulation of liver L-type pyruvate kinase by a phosphorylation mechanism has been intensively studied for several years. Ljungstrom et al. were the first to report that rat liver L-type pyruvate kinase can be phosphorylated by an adenosine-3',5'-phosphatedependent (cyclic-AMP-dependent) protein kinase [l]. Phosphorylation of pig-liver L-type enzyme has also been reported [2,3]. Glucagon induces phosphorylation of liver L-type pyruvate kinase in vivo through a cyclic-AMP-dependent mechanism [4-61. This phosphorylation of L-type pyruvate kinase causes important changes in the kinetics of the enzyme: decreased affinity for phosphoenolpyruvate, and increased inhibition by the allosteric effectors ATP and alanine [2,7-111. These kinetic modifications are expected to play an important physiological role in the dynamic balance between glycolysis and gluconeogenesis by blocking the pyruvate kinase reaction when gluconeogenesis is the predominant pathway, thus impairing a futile cycle between phosphoenolpyruvate and pyruvate.Ahhreviutzon. Cyclic AMP, adenosine 3',5'-phosphate.We have previously shown that human L-type pyruvate kinase seems to undergo, after its synthesis, a progressive proteolytic processing, which is different in liver and red cells. In these latter cells the Lb precursor (composed of four identical subunits of M , 63000) is partially proteolysed with red cell maturation and aging, and this gives rise to heterotetrameric forms composed of L and partially proteolysed subunits [12,13]. In liver the L-type pyruvate kinase consists almost entirely of a form composed of four identical subunits of M , about 60000 closely resembling trypsin-treated L-type subunits [12-141. We thus hypothesized that in liver the L subunits are immediately proteolysed by a specific proteolytic system after they have been synthesized. We [13] and other authors [15] proved that proteolytic processing of L-type pyruva...

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Section: Discussionmentioning

confidence: 78%

Phosphorylation of Human Erythrocyte Pyruvate Kinase by Soluble Cyclic‐AMP‐Dependend Protein Kinases

Marie

Buc

Simon

et al. 1980

European Journal of Biochemistry

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“…Thus, exposure of animals or cell cultures to either hyperoxia, forced exercise, ischemia-reperfusion, rapid correction of hyponatremia, paraquat toxicity, magnesium deficiency, ozone, neutrophil activation, cigarette smoking, x-radiation, chronic alcohol treatment, or mixed function oxidation systems leads to an increase in the level of oxidized protein. 4 Protein Oxidation and Aging-Aging is associated with the accumulation of inactive or less active, more heat-labile forms of numerous enzymes (25,26). The possibility that these age-related changes are due, at least in part, to oxidative modification is indicated by the facts.…”

Section: Generation Of Protein Carbonyl Derivativesmentioning

confidence: 99%

Protein Oxidation in Aging, Disease, and Oxidative Stress

Berlett

Stadtman

1997

Journal of Biological Chemistry

3,006

2,064

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The demonstration that oxidatively modified forms of proteins accumulate during aging, oxidative stress, and in some pathological conditions has focused attention on physiological and nonphysiological mechanisms for the generation of reactive oxygen species (ROS) 1 and on the modification of biological molecules by various kinds of ROS. Basic principles that govern the oxidation of proteins by ROS were established in the pioneering studies of Swallow (1), Garrison (2, 3), and Scheussler and Schilling (4) who characterized reaction products formed when proteins were exposed to ionizing radiation under conditions where only ⅐ OH, O 2. , or a mixture of both was made available. Results of these studies demonstrated that the modification of proteins is initiated mainly by reactions with ⅐ OH; however, the course of the oxidation process is determined by the availability of O 2 and O 2 . or its protonated form (HO ⅐ 2 ). Collectively, these ROS can lead to oxidation of amino acid residue side chains, formation of protein-protein cross-linkages, and oxidation of the protein backbone resulting in protein fragmentation. In the meantime, it has been shown that other forms of ROS may yield similar products and that transition metal ions can substitute for ⅐ OH and O 2 . in some of the reactions.

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“…These multiple forms include allelic variants, gene products of duplicated structural loci, or electromorphs which result from spontaneous aging of the primary isozyme (Harris, 1980). Isozymic forms may also be generated by specific posttranslational events such as proteolytic cleavage and covalent ligand binding (see Wold, 1981) and noncovalent binding of cofactors (Dreyfus et al, 1978). In addition to posttranslational events, examples of multiple isozymes from a single structural locus have now been shown to be produced by (1) gene reorganization (Early et al, 1980;Nasmyth and Tatchell, 1980) and (2) differential transcript processing (Crabtree and Kant, 1982;Marie et al, 1982;Young et al, 1981;Levin et al, 1982;Capetanaki et al, 1983;Schwarzbauer et al, 1983;Nabeshima et al, 1984).…”

Section: Introductionmentioning

confidence: 99%