Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo

Bella, Deborah; Hirschberger, Lawrence L.; Hosokawa, Yu; Stipanuk, Martha H.

doi:10.1152/ajpendo.1999.276.2.e326

Cited by 47 publications

(75 citation statements)

References 24 publications

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“…Protein was concentrated on Vivaspin centrifugation concentrators (GE Healthcare) to the appropriate concentrations for the subsequent experiments. As expected, P. aeruginosa CDO homologue preparations resolved into a single band when subjected to SDS-PAGE, revealing the absence of a posttransla-tional modification present in mammalian CDO (53)(54)(55)(56) (Fig. 3).…”

Section: Methodssupporting

confidence: 64%

The Cysteine Dioxygenase Homologue from Pseudomonas aeruginosa Is a 3-Mercaptopropionate Dioxygenase

Tchesnokov

Fellner

Siakkou

et al. 2015

Journal of Biological Chemistry

117

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Background: Thiol dioxygenation is catalyzed by enzymes specific for each substrate. Results: Kinetic, structural, and spectroscopic data describe an enzyme from P. aeruginosa that is a 3-mercaptopropionate dioxygenase with secondary cysteine dioxygenase activity. Conclusion: An arginine to glutamine switch and the absence of a cis-peptide bond correlate with substrate preference. Significance: Characterization of this enzyme deepens our understanding of substrate specificity in thiol dioxygenases.

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Section: Methodssupporting

confidence: 64%

The Cysteine Dioxygenase Homologue from Pseudomonas aeruginosa Is a 3-Mercaptopropionate Dioxygenase

Tchesnokov

Fellner

Siakkou

et al. 2015

Journal of Biological Chemistry

117

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“…Thus, although most of the body's hypotaurine/taurine pool is in the form of taurine, hypotaurine is a better indicator of active taurine biosynthesis. Previous work has shown that CDO activity plays the major role in determining the flux of cysteine to hypotaurine/taurine (1,2,5). Cysteinesulfinate decarboxyase, which catalyzes the decarboxylation of cysteinesulfinate to hypotaurine, is highly expressed in pancreas and kidney as well as in liver (24).…”

Section: Discussionmentioning

confidence: 99%

Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase

Ueki

Roman

Hirschberger

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Because hepatic cysteine dioxygenase (CDO) appears to play the major role in controlling cysteine catabolism in the intact rat, we characterized the effect of a lack of hepatic CDO on the regulation of cysteine and its metabolites at the whole body level. In mice with liver-specific deletion of CDO expression, hepatic and plasma cysteine levels increased. In addition, in mice with liver-specific deletion of CDO expression, the abundance of CDO and the proportion of CDO existing as the mature, more active isoform increased in extrahepatic tissues that express CDO (kidney, brown fat, and gonadal fat). CDO abundance was also increased in the pancreas, where most of the enzyme in both control and liver CDO-knockout mice was in the more active isoform. This upregulation of CDO concentration and active-site cofactor formation were not associated with an increase in CDO mRNA and thus presumably were due to a decrease in CDO degradation and an increase in CDO cofactor formation in association with increased exposure of extrahepatic tissues to cysteine in mice lacking hepatic CDO. Extrahepatic tissues of liver CDO-knockout mice also had higher levels of hypotaurine, consistent with increased metabolism of cysteine by the CDO/cysteinesulfinate decarboxylase pathway. The hepatic CDO-knockout mice were able to maintain normal levels of glutathione, taurine, and sulfate. The maintenance of taurine concentrations in liver as well as in extrahepatic tissues is particularly notable, since mice were fed a taurine-free diet and liver is normally considered the major site of taurine biosynthesis. This redundant capacity for regulation of cysteine concentrations and production of hypotaurine/taurine is additional support for the body's robust mechanisms for control of body cysteine levels and indicates that extrahepatic tissues are able to compensate for a lack of hepatic capacity for cysteine catabolism.

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“…In support of this, our results showed that cysteine supplementation significantly decreased the proportion of protein-bound homocysteine and increased the proportion of non-proteinbound homocysteine in the plasma of rats fed 15S (experiment 3). The lack of cysteine supplementationinduced increase in plasma cysteine concentration observed in rats fed 25C and 25S appears to be due to higher activities of cysteine dioxygenase, the rate-limiting enzyme of cysteine metabolism (1), since it has been shown that the activity of this enzyme increases in response to increase in dietary levels of protein and sulfur amino acids such as methionine and cysteine (35,36).…”

Section: Discussionmentioning

confidence: 99%

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Kawakami

Ohuchi

Morita

et al. 2009

J Nutr Sci Vitaminol

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Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...

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Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo

Cited by 47 publications

References 24 publications

The Cysteine Dioxygenase Homologue from Pseudomonas aeruginosa Is a 3-Mercaptopropionate Dioxygenase

The Cysteine Dioxygenase Homologue from Pseudomonas aeruginosa Is a 3-Mercaptopropionate Dioxygenase

Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

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