乙酰化
中文名称
通路描述
N-乙酰转移酶（NATs；EC 2.3.1.5）利用乙酰 CoA 进行乙酰化结合反应。这是芳香胺（R-NH2，转化为芳香酰胺 R-NH-COCH3）和杂环胺（R-NH-NH2，转化为 R-NH-NH-COCH3）结合的首选途径。脂肪族胺不是 NAT 的底物。基本反应为乙酰 CoA + 芳香胺 = CoA + N-乙酰芳香胺。NATs 位于胞质，人类中有 2 个异构体表达，NAT1 和 NAT2。第三个异构体 NATP 是假基因且不表达。NAT2 基因中的突变降低了 NAT2 活性。这种慢乙酰化表型与抗结核药物异烟肼的正常快速乙酰化相比首次被发现，慢乙酰化表型的发病率在中东人群（70%）中很高，在欧洲人、美国人和澳大利亚人（平均 50%）中平均，而在亚洲（中国、日本和韩国，乒乓 Bi-Bi 机制发生两步。在第一步中，乙酰基从乙酰 CoA 转移到 NAT 中的半胱氨酸残基，随后释放辅酶 A。在第二步中，乙酰基从乙酰化的 NAT 释放到底物上，随后再生酶。
英文描述
Acetylation N-acetyltransferases (NATs; EC 2.3.1.5) utilize acetyl Co-A in acetylation conjugation reactions. This is the preferred route of conjugating aromatic amines (R-NH2, converted to aromatic amides R-NH-COCH3) and hydrazines (R-NH-NH2, converted to R-NH-NH-COCH3). Aliphatic amines are not substrates for NAT. The basic reaction is
Acetyl-CoA + an arylamine = CoA + an N- acetylarylamine
NATs are cytosolic and in humans, 2 isoforms are expressed, NAT1 and NAT2. A third isoform, NATP, is a pseudogene and is not expressed. The NAT2 gene contains mutations that decrease NAT2 activity. This mutations was first seen as slow acetylation compared to the normal, fast acetylation of the antituberculosis drug isoniazid. Incidence of the slow acetylator phenotype is high in Middle Eastern populations (70%), average (50%) in Europeans, Americans and Australians and low in Asians (ping-pong Bi-Bi mechanism. In the first step, the acetyl group from acetyl-CoA is transferred to a cysteine residue in NAT, with consequent release of coenzyme-A. In the second step, the acetyl group is released from the acetylated NAT to the substrate, subsequently regenerating the enzyme.
Acetyl-CoA + an arylamine = CoA + an N- acetylarylamine
NATs are cytosolic and in humans, 2 isoforms are expressed, NAT1 and NAT2. A third isoform, NATP, is a pseudogene and is not expressed. The NAT2 gene contains mutations that decrease NAT2 activity. This mutations was first seen as slow acetylation compared to the normal, fast acetylation of the antituberculosis drug isoniazid. Incidence of the slow acetylator phenotype is high in Middle Eastern populations (70%), average (50%) in Europeans, Americans and Australians and low in Asians (ping-pong Bi-Bi mechanism. In the first step, the acetyl group from acetyl-CoA is transferred to a cysteine residue in NAT, with consequent release of coenzyme-A. In the second step, the acetyl group is released from the acetylated NAT to the substrate, subsequently regenerating the enzyme.
所含基因
2 个基因