Cysteamine Dioxygenase: Evidence for the Physiological Conversion of Cysteamine to Hypotaurine in Rat and Mouse Tissues

Coloso, Relicardo M.; Hirschberger, Lawrence L.; Dominy, John E.; Lee, Jeong-In; Stipanuk, Martha H.

doi:10.1007/978-0-387-33504-9_3

Cited by 48 publications

(54 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, all of these studies added an exogenous electron-donating cofactor-like compound such as sulfide, methylene blue, or hydroxylamine to attain activity. Recent work from our laboratory, however, demonstrated that directly measuring hypotaurine production by HPLC is a sensitive and accurate means for assessing cysteamine dioxygenase activity (19). Using this approach we observed that exogenous electron-donating cofactors are not required for cysteamine dioxygenase activity in crude tissue extracts (19).…”

Section: Resultsmentioning

confidence: 83%

“…The reactions were stopped with the addition of 200 l of 5% w/v sulfosalicylic acid (SSA). Hypotaurine production was measured by derivatization of sample with o-phthaldialdehyde and detection of derivatized products by high performance liquid chromatography coupled with fluorescence detection as previously described (19). Under our standard assay conditions we found that a small amount (Ͻ10%) of hypotaurine was spontaneously oxidized to taurine.…”

Section: Methodsmentioning

confidence: 95%

“…Cysteamine, on the other hand, has only one known function, and that is as a precursor for the formation of hypotaurine, which is subsequently oxidized to taurine. The rate of cysteamine production as a result of coenzyme A breakdown is not well understood (33), but it is clear that cysteamine levels are not as dramatically affected by dietary habits as are cysteine levels (12,19). Coenzyme A degradation is suspected to be a constitutive process that occurs in all tissues, although some tissues such as brain and heart may have exceptionally high coenzyme A turnover rates (33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

“…The sequence alignment was prepared using AlignX software (Vector NTI, Invitrogen) and the Blosum62mt scoring matrix. Accession numbers for the proteins shown in the alignment are as follows: thesis of hypotaurine and taurine in vivo (19). There is also evidence that cyst(e)amine could serve as an endogenous regulator of immune system activity (20,21) as well as a potential therapeutic agent for the treatment of Huntington disease (30 -32).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Discovery and Characterization of a Second Mammalian Thiol Dioxygenase, Cysteamine Dioxygenase

Dominy¹,

Simmons

Hirschberger

et al. 2007

Journal of Biological Chemistry

Self Cite

155

149

View full text Add to dashboard Cite

There are only two known thiol dioxygenase activities in mammals, and they are ascribed to the enzymes cysteine dioxygenase (CDO) and cysteamine (2-aminoethanethiol) dioxygenase (ADO). Although many studies have been dedicated to CDO, resulting in the identification of its gene and even characterization of the tertiary structure of the protein, relatively little is known about cysteamine dioxygenase. The failure to identify the gene for this protein has significantly hampered our understanding of the metabolism of cysteamine, a product of the constitutive degradation of coenzyme A, and the synthesis of taurine, the final product of cysteamine oxidation and the second most abundant amino acid in mammalian tissues. In this study we identified a hypothetical murine protein homolog of CDO (hereafter called ADO) that is encoded by the gene Gm237 and belongs to the DUF1637 protein family. When expressed as a recombinant protein, ADO exhibited significant cysteamine dioxygenase activity in vitro. The reaction was highly specific for cysteamine; cysteine was not oxidized by the enzyme, and structurally related compounds were not competitive inhibitors of the reaction. When overexpressed in HepG2/C3A cells, ADO increased the production of hypotaurine from cysteamine. Similarly, when endogenous expression of the human ADO ortholog C10orf22 in HepG2/C3A cells was reduced by RNAmediated interference, hypotaurine production decreased. Western blots of murine tissues with an antibody developed against ADO showed that the protein is ubiquitously expressed with the highest levels in brain, heart, and skeletal muscle. Overall, these data suggest that ADO is responsible for endogenous cysteamine dioxygenase activity.There are many different processes in mammalian cells that result in the oxidation of thiol groups. Because of their reactivity, free sulfhydryl groups are highly susceptible to oxidation that results in the formation of disulfides, sulfenates, sulfinates, and sulfonates. Many of these reactions occur nonenzymatically, principally as a consequence of adventitious free radicals arising from aerobic respiration. Nevertheless, there are a small number of thiol oxidation reactions that are known to occur directly via enzymatic catalysis. The enzymes that catalyze these reactions show a high degree of substrate specificity and confer to cells the advantage of being able to precisely regulate the level of a particular reduced thiol.One interesting subset of the enzymes capable of specifically oxidizing free sulfhydryl groups are the thiol dioxygenases. In mammals this family comprises only two known proteins: cysteine dioxygenase (CDO, 3 EC 1.13.11.20) and cysteamine dioxygenase (EC 1.13.11.19). CDO adds two atoms of oxygen to free cysteine to yield cysteine sulfinic acid, whereas cysteamine dioxygenase adds two atoms of oxygen to free cysteamine (2-aminoethanethiol) to form hypotaurine (Fig. 1). The activities for these two proteins were first reported in mammalian tissues almost 40 years ago (1, 2). Since that time, howev...

show abstract

Section: Resultsmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Discovery and Characterization of a Second Mammalian Thiol Dioxygenase, Cysteamine Dioxygenase

Dominy¹,

Simmons

Hirschberger

et al. 2007

Journal of Biological Chemistry

Self Cite

155

149

View full text Add to dashboard Cite

show abstract

“…In its turn, cysteamine is constitutively produced by all tissues in human and animal body as part of the coenzyme A (an acyl carrier group required for many metabolic processes) catabolic pathway [19]. Recent work has shown that many tissues are capable of converting cysteamine to hypotaurine and subsequently to taurine in vivo [20]. Cysteamine seems to be the main source of taurine, the second most abundant amino acid in the brain, with membrane-stabilizing and antioxidant properties [21].…”

Section: Discussionmentioning

confidence: 99%

Comparative study of the antioxidant activity of some thiol-containing substances

2012

View full text Add to dashboard Cite

show abstract

Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine

Wang

Griffith

et al. 2018

Angewandte Chemie

View full text Add to dashboard Cite

Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by the ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Reported herein is the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C−S) bond. By genetically incorporating an unnatural amino acid, 3,5‐difluoro‐tyrosine (F2‐Tyr), specifically into Tyr222 of human ADO, an autocatalytic oxidative carbon–fluorine bond activation and fluoride release were identified by mass spectrometry and 19F NMR spectroscopy. These results suggest that the cofactor biogenesis is executed by a powerful oxidant during an autocatalytic process. Unlike that of cysteine dioxygenase, the crosslinking results in a minimal structural change of the protein and it is not detectable by routine low‐resolution techniques. Finally, a new sequence motif, C‐X‐Y‐Y(F), is proposed for identifying the Cys‐Tyr crosslink.

show abstract

Cysteamine Dioxygenase: Evidence for the Physiological Conversion of Cysteamine to Hypotaurine in Rat and Mouse Tissues

Cited by 48 publications

References 23 publications

Discovery and Characterization of a Second Mammalian Thiol Dioxygenase, Cysteamine Dioxygenase

Discovery and Characterization of a Second Mammalian Thiol Dioxygenase, Cysteamine Dioxygenase

Comparative study of the antioxidant activity of some thiol-containing substances

Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine

Contact Info

Product

Resources

About