Biomaterial Database

Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion. 2009

Tsunehiro Shintani, and Takuya Iwabuchi, and Tomoyoshi Soga, and Yuichiro Kato, and Takehiro Yamamoto, and Naoharu Takano, and Takako Hishiki, and Yuki Ueno, and Satsuki Ikeda, and Tadayuki Sakuragawa, and Kazuo Ishikawa, and Nobuhito Goda, and Yuko Kitagawa, and Mayumi Kajimura, and Kenji Matsumoto, and Makoto Suematsu

Department of Biochemistry and Integrative Medical Biology, Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.

Carbon monoxide (CO) is a stress-inducible gas generated by heme oxygenase (HO) eliciting adaptive responses against toxicants; however, mechanisms for its reception remain unknown. Serendipitous observation in metabolome analysis in CO-overproducing livers suggested roles of cystathionine beta-synthase (CBS) that rate-limits transsulfuration pathway and H(2)S generation, for the gas-responsive receptor. Studies using recombinant CBS indicated that CO binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity, whereas nitric oxide (NO) forms 5-coordinated structure without inhibiting it. The CO-overproducing livers down-regulated H(2)S to stimulate HCO(3) (-)-dependent choleresis: these responses were attenuated by blocking HO or by donating H(2)S. Livers of heterozygous CBS knockout mice neither down-regulated H(2)S nor exhibited the choleresis while overproducing CO. In the mouse model of estradiol-induced cholestasis, CO overproduction by inducing HO-1 significantly improved the bile output through stimulating HCO(3) (-) excretion; such a choleretic response did not occur in the knockout mice. CONCLUSIONS Results collected from metabolome analyses suggested that CBS serves as a CO-sensitive modulator of H(2)S to support biliary excretion, shedding light on a putative role of the enzyme for stress-elicited adaptive response against bile-dependent detoxification processes.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D002248	Carbon Monoxide	Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)	Monoxide, Carbon
D003541	Cystathionine beta-Synthase	A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to HYPERHOMOCYSTEINEMIA and HOMOCYSTINURIA. EC 4.2.1.22.	Serine Sulfhydrase,beta-Thionase,Cystathionine Synthetase,Cystathionine beta Synthase,Sulfhydrase, Serine,Synthetase, Cystathionine,beta Thionase,beta-Synthase, Cystathionine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001646	Bile	An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.	Biliary Sludge,Sludge, Biliary
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055442	Metabolome	The dynamic collection of metabolites which represent a cell's or organism's net metabolic response to current conditions.	Metabolic Profile,Metabolic Profiles,Metabolomes,Profile, Metabolic,Profiles, Metabolic