Cysteinesulfinate metabolism. altered partitioning between transamination and decarboxylation following administration of beta-methyleneaspartate.
Cysteinesulfinate metabolism. altered partitioning between transamination and decarboxylation following administration of beta-methyleneaspartate.
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DOI：
10.1016/s0021-9258(18)33025-4
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发表时间：
1983-02
期刊：
影响因子：
--
通讯作者：
O. Griffith
中科院分区：
文献类型：
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作者：
O. Griffith
L-半胱氨酸亚磺酸盐是 L-半胱氨酸的一种重要的定量分解代谢物，是半胱氨酸亚磺酸脱羧酶和谷氨酸-草酰乙酸转氨酶的底物。前一种酶启动生成牛磺酸的途径；后一种酶启动生成牛磺酸的途径。后一种酶形成β-亚磺酰丙酮酸，其自发分解为丙酮酸和SO2。在本研究中，通过给小鼠施用 L-[1-14C]半胱亚磺酸盐（通过两种途径代谢为 14CO2）或 L-[3-14C]半胱亚磺酸盐（仅在不形成牛磺酸时才转化为 14CO2）来评估半胱氨酸亚磺酸盐在这两种途径之间的体内分配。 6小时内，呼吸性14CO2占注射的[1-14C]半胱亚磺酸盐的90%，而注射的[3-14C]半胱亚磺酸盐中只有18%被回收为14CO2。当对[1-14C]-和[3-14C]丙酮酸形成的 14CO2 的差异以及放射性标记的亚牛磺酸形成的 14CO2 的少量数据进行校正时，得出的结论是，所施用的半胱亚磺酸盐中约 85% 脱羧为亚牛磺酸，而约 15% 被转氨。形成的亚牛磺酸中，大约 90% 被氧化为牛磺酸。 β-亚甲基-DL-天冬氨酸，一种不可逆的谷氨酸-草酰-乙酸转氨酶抑制剂（Cooper, A.J.L., Fitzpatrick, S. M., Kaufman, C., and Dowd, P. (1982) J. Am. Chem. Soc. 104, 332-334）被给予小鼠，期望将半胱氨酸亚磺酸盐转化为亚牛磺酸会增加。令人惊讶的是，半胱亚磺酸酯转氨基作用的程度增加了约3倍。其他研究表明，β-亚甲基天冬氨酸是纯化的大鼠肝脏半胱氨酸亚磺酸脱羧酶的有效、不可逆抑制剂，并且体内脱羧酶的失活优于转氨酶的失活。高度纯化的半胱亚磺酸脱羧酶还可将 L-天冬氨酸脱羧为 β-丙氨酸，并非常缓慢地将谷氨酸脱羧为 γ-氨基丁酸。该酶对 α-甲基半胱氨酸亚磺酸盐或 α-甲基天冬氨酸盐没有活性； α-甲基-DL-[1-14C]半胱亚磺酸盐不被小鼠代谢。
L-Cysteinesulfinate, a quantitatively important catabolite of L-cysteine, is a substrate of both cysteinesulfinate decarboxylase and glutamate-oxaloacetate transaminase. The former enzyme initiates a pathway leading to taurine; the latter enzyme forms beta-sulfinyl-pyruvate, which spontaneously decomposes to pyruvate and SO2. In the present studies, the in vivo partitioning of cysteinesulfinate between these two pathways was evaluated by administering to mice L-[1-14C]cysteinesulfinate, which is metabolized to 14CO2 by both pathways, or L-[3-14C]cysteinesulfinate, which is converted to 14CO2 only if taurine is not formed. Within 6 h, respiratory 14CO2 accounted for 90% of the [1-14C]cysteinesulfinate injected, whereas only 18% of administered [3-14C]cysteinesulfinate was recovered as 14CO2. When the data are corrected for differences in the formation of 14CO2 from [1-14C]- and [3-14C]pyruvate and for a small formation of 14CO2 from radiolabeled hypotaurine, it is concluded that approximately 85% of administered cysteinesulfinate is decarboxylated to hypotaurine, whereas approximately 15% is transaminated. Of the hypotaurine formed, approximately 90% is oxidized to taurine. beta-Methylene-DL-aspartate, an irreversible inhibitor of glutamate-oxal-oacetate transaminase (Cooper, A.J.L., Fitzpatrick, S. M., Kaufman, C., and Dowd, P. (1982) J. Am. Chem. Soc. 104, 332-334) was given to mice with the expectation that conversion of cysteinesulfinate to hypotaurine would be increased. Surprisingly, the extent of cysteinesulfinate transamination increased about 3-fold. Additional studies indicate that beta-methyleneaspartate is a potent, irreversible inhibitor of purified rat liver cysteinesulfinate decarboxylase and that inactivation of the decarboxylase predominates over inactivation of the transaminase in vivo. Highly purified cysteinesulfinate decarboxylase is also shown to decarboxylate L-aspartate to beta-alanine and, very slowly, glutamate to gamma-aminobutyrate. The enzyme is not active toward alpha-methylcysteinesulfinate or alpha-methylaspartate; alpha-methyl-DL-[1-14C]cysteinesulfinate is not metabolized by the mouse.