INHIBITION INVITRO OF THE ENZYMES OF THE OXIDATIVE PATHWAY OF TRYPTOPHAN-METABOLISM AND OF NICOTINAMIDE NUCLEOTIDE SYNTHESIS BY BENSERAZIDE, CARBIDOPA AND ISONIAZID
INHIBITION INVITRO OF THE ENZYMES OF THE OXIDATIVE PATHWAY OF TRYPTOPHAN-METABOLISM AND OF NICOTINAMIDE NUCLEOTIDE SYNTHESIS BY BENSERAZIDE, CARBIDOPA AND ISONIAZID
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DOI：
10.1016/0006-2952(80)90544-4
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发表时间：
1980-01-01
影响因子：
5.8
通讯作者：
BENDER, DA
中科院分区：
文献类型：
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作者：
BENDER, DA
用大鼠肝脏制备物研究了3种肼衍生物对色氨酸氧化途径和烟酰胺核苷酸合成酶的影响。使用的化合物是苄丝肼[N-丝氨酰-N“-（2，3，4-三羟基苄基）-肼]和卡比多巴[α-氨基苯磺酸]。肼基-3，4-二羟基苯基-α-甲基丙酸]，2种芳香族氨基酸脱羧酶抑制剂[EC 4.1.1.28]。所有3种药物均抑制色氨酸加氧酶和犬尿氨酸酶，其浓度与对患者或实验动物给药后体内遇到的浓度相同。异烟肼抑制3-羟基邻氨基苯甲酸氧化酶和烟酰胺磷酸核糖基转移酶。这2种酶在药物浓度远远超过体内可能遇到的浓度时受到显著抑制。根据体外酶抑制研究，尽管有烟酸缺乏的生化证据，但无法解释为什么接受异烟肼（未补充维生素B6）治疗的患者会出现临床糙皮病，而接受苄丝肼或卡比多巴治疗的患者则不会。这种差异可能是由于2组患者膳食烟酸摄入量的差异，或由于各组代谢的差异及其与体外不明显的体内酶的相互作用。
The effects of 3 hydrazine derivatives on the enzymes of the tryptophan oxidative pathway and of nicotinamide nucleotide synthesis were studied using preparations from rat liver. The compounds used were Benserazide [N-seryl-N''-(2,3,4-trihydroxybenzyl)-hydrazine] and Carbidopa [.alpha.-hydrazino-3,4-dihydroxyphenyl-.alpha.-methylpropionic acid], 2 inhibitors of aromatic amino acid decarboxylase [EC 4.1.1.28]. All 3 drugs inhibited tryptophan oxygenase and kynureninase, at concentrations that are encountered in vivo after administration to patients or experimental animals. Isoniazid inhibited 3-hydroxy-anthranilate oxidase and nicotinamide phosphoribosyltransferase. The 2 enzymes were inhibited significantly at concentrations of the drug far in excess of those likely to be encountered in vivo. On the basis of the in vitro enzyme inhibition studies, it is not possible to explain why patients treated with isoniazid (without supplementary vitamin B6) develop clinical pellagra, while those treated with Benserazide or Carbidopa do not, despite biochemical evidence of niacin deficiency. The difference may be due to differences in the intake of dietary niacin in the 2 groups of patients or to differences in the metabolism of the groups and in their interactions with enzymes in vivo that are not apparent in vitro.