Regulation of oxidative degradation of <scp>l</scp>-lysine in rat liver mitochondria

Ścisłowski, P. W. D.; Foster, A. R.; Fuller, M. F.

doi:10.1042/bj3000887

Cited by 22 publications

(9 citation statements)

References 41 publications

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“…We also observe an upregulation of saccharopine dehydrogenase (Aass), which is involved in lysine catabolism: this upregulation is also suppressed in sugar condition. Consistent with this finding, treatment with glucagon has demonstrated increased flux through lysine catabolism pathway (58). There is also downregulation of the gene encoding glutamine synthetase (Glu1), a key enzyme in amino acid metabolism.…”

Section: Urea Cycle and Amino Acid Metabolismmentioning

confidence: 76%

Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

Bauer

Hamm

Bonaus

et al. 2004

Physiological Genomics

142

111

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We have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high-density microarrays. From approximately 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone (DHEA) hormonal pathways, urea cycle and S-adenosylmethionine-based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction-dependent life-span extension.

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Section: Urea Cycle and Amino Acid Metabolismmentioning

confidence: 76%

Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

Bauer

Hamm

Bonaus

et al. 2004

Physiological Genomics

142

111

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“…One of the most common modifications is oxidation of labile amino acid side chains, which is induced by reactive oxygen species. 1 Although protein oxidation can occur at cysteine, tryptophan, lysine and other amino acids, [2][3][4] methionine is often the most susceptible residue to oxidation. 5,6 The most common product of methionine oxidation is methionine sulfoxide, which is more polar and less hydrophobic than methionine.…”

Section: Introductionmentioning

confidence: 99%

Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn

et al. 2009

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Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics. Methionine oxidation may limit the product's clinical efficacy or stability. We have studied kinetics of methionine oxidation in the Fc portion of the human IgG2 and its impact on the interaction with FcRn and Protein A. Our results confirm previously published observations for IgG1 that two analogous solvent-exposed methionine residues in IgG2, Met 252 and Met 428, oxidize more readily than the other methionine residue, Met 358, which is buried inside the Fc. Met 397, which is not present in IgG1 but in IgG2, oxidizes at similar rate as Met 358. Oxidation of two labile methionines, Met 252 and Met 428, weakens the binding of the intact antibody with Protein A and FcRn, two natural protein binding partners. Both of these binding partners share the same binding site on the Fc. Additionally, our results shows that Protein A may serve as a convenient and inexpensive surrogate for FcRn binding measurements.

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“…These increases in enzymic activity were accompanied by a significant increase in Lor\Sdh mRNA levels (Figure 7), suggesting that the induction in LOR\SDH under starvation might, at least in part, be the result of an increased transcription rate, as with a number of amino acid-degrading enzymes [39]. A previous paper showed a marked induction in rat liver LOR activity after the administration of glucagon [49]. This finding, together with our results on starved mice, points to an important involvement of LOR\SDH and lysine degradation itself in the energetic balance.…”

Section: Discussionmentioning

confidence: 76%

Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse

Papes

Kemper

Cord-Neto

et al. 1999

Biochemical Journal

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Lysine-oxoglutarate reductase and saccharopine dehydrogenase are enzymic activities that catalyse the first two steps of lysine degradation through the saccharopine pathway in upper eukaryotes. This paper describes the isolation and characterization of a cDNA clone encoding a bifunctional enzyme bearing domains corresponding to these two enzymic activities. We partly purified those activities from mouse liver and showed for the first time that both a bifunctional lysine-oxoglutarate reductase/saccharopine dehydrogenase and a monofunctional saccharopine dehydrogenase are likely to be present in this organ. Northern analyses indicate the existence of two mRNA species in liver and kidney. The longest molecule, 3.4 kb in size, corresponds to the isolated cDNA and encodes the bifunctional enzyme. The 2.4 kb short transcript probably codes for the monofunctional dehydrogenase. Sequence analyses show that the bifunctional enzyme is likely to be a mitochondrial protein. Furthermore, enzymic and expression analyses suggest that lysine-oxoglutarate reductase/saccharopine dehydrogenase levels increase in livers of mice under starvation. Lysine-injected mice also show an increase in lysine-oxoglutarate reductase and saccharopine dehydrogenase levels.

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Regulation of oxidative degradation of l-lysine in rat liver mitochondria

Cited by 22 publications

References 41 publications

Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn

Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse

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