Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.
Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.
复制标题
人过氧化物酶体 3-氧代酰基辅酶 A 硫解酶缺乏症。
DOI：
10.1073/pnas.84.8.2494
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发表时间：
1987
影响因子：
11.1
通讯作者：
Tager,JM
中科院分区：
文献类型：
--
作者：
Schram,AW;Goldfischer,S;vanRoermund,CW;Brouwer-Kelder,EM;Collins,J;Hashimoto,T;Heymans,HS;vandenBosch,H;Schutgens,RB;Tager,JM
我们研究了肝脏中的过氧化物酶体β-氧化系统，该患者的临床特征与肝肾综合征（Zellweger）患者相似，并且体液中极长链脂肪酸和胆汁酸生物合成中间体水平升高。脂肪酸的过氧化物酶体β-氧化，测量为[14 C]棕榈酰辅酶A的[14 C]乙酰基单位的氰化物不敏感形成，在患者中非常低（低于对照受试者值的10%）。使用过氧化物酶体β-氧化酶的抗体的免疫印迹实验表明过氧化物酶体3-氧代酰基-CoA硫解酶（酰基-CoA：乙酰基-CoA C-酰基转移酶，EC 2.3.1.16）是缺陷的。将纯化的大鼠肝脏过氧化物酶体3-氧代酰基-CoA硫解酶添加到含有来自患者的肝匀浆的反应混合物中恢复了过氧化物酶体β-氧化。我们得出结论，过氧化物酶体3-氧代酰基-CoA硫解酶的缺乏是负责非常低的过氧化物酶体β-氧化活性和非常长链的脂肪酸和中间体的积累在胆汁酸的生物合成。此外，发现极长链脂肪酸和异常胆汁酸在该患者中积累表明，单个过氧化物酶体3-氧代酰基-CoA硫解酶参与极长链脂肪酸和粪甾烷酸的氧化链缩短。
We investigated the peroxisomal beta-oxidation system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zellweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal beta-oxidation of fatty acids, measured as the cyanide-insensitive formation of [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (less than 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal beta-oxidation enzymes indicated that peroxisomal 3-oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) was deficient. Addition of purified rat-liver peroxisomal 3-oxoacyl-CoA thiolase to a reaction mixture containing liver homogenate from the patient restored peroxisomal beta-oxidation. We conclude that the deficiency of peroxisomal 3-oxoacyl-CoA thiolase is responsible for the very low peroxisomal beta-oxidation activity and for the accumulation of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. Furthermore, the finding that both very-long-chain fatty acids and abnormal bile acids accumulate in this patient suggests that a single peroxisomal 3-oxoacyl-CoA thiolase is involved in the oxidative chain shortening of both very-long-chain fatty acids and the coprostanoic acids.