Rawal S, Mendoza K M, Reed K M, Coulombe R A
Graduate Toxicology Program and Department of Veterinary Sciences, Utah State University, Logan, Utah 84322, USA.
Cytogenet Genome Res. 2009;125(1):67-73. doi: 10.1159/000218748. Epub 2009 Jul 14.
Cytochromes P450 (P450 for protein; CYP for gene) are a superfamily of membrane-bound hemoproteins that oxidize a large number of endogenous and exogenous compounds. Through oxidation reactions, these enzymes are often responsible for the toxic and carcinogenic effects of natural food-borne toxicants, such as the mycotoxin aflatoxin B1 (AFB1). Previous studies in our laboratory have shown that the extreme sensitivity of turkeys to AFB1 is in part explained by efficient hepatic P450-mediated epoxidation to the toxic and reactive metabolite the exo-AFB1-8,9-epoxide (AFBO). Using 3'-5'-rapid amplification of cDNA ends (RACE), we amplified CYP3A37 from turkey liver RNA, the E. coli-expressed protein which efficiently epoxidates AFB(1). Turkey CYP3A37 has an ORF of 1512 bp, and the protein is predicted to be 504 amino acids with 97% homology to chicken CYP3A37. The turkey gene is organized into 13 exons and 12 introns. A single nucleotide polymorphism in the 11th intron was used to assign CYP3A37 to turkey linkage group 10 (corresponding to chicken chromosome 14, GGA14). Because of the important role of P450s in the extreme sensitivity of turkeys to the toxic effects of AFB(1), this study will contribute to the identifying allelic variants of this important gene in poultry.
细胞色素P450（蛋白质为P450；基因则为CYP）是一类膜结合血红蛋白超家族，可氧化大量内源性和外源性化合物。通过氧化反应，这些酶通常导致天然食源毒物产生毒性和致癌作用，比如霉菌毒素黄曲霉毒素B1（AFB1）。我们实验室之前的研究表明，火鸡对AFB1极度敏感，部分原因是肝脏中P450高效介导的环氧化作用生成了有毒且具反应活性的代谢产物外-AFB1-8,9-环氧化物（AFBO）。我们利用3'-5'-cDNA末端快速扩增法（RACE），从火鸡肝脏RNA中扩增出CYP3A37，该基因在大肠杆菌中表达的蛋白质能够高效地将AFB1环氧化。火鸡CYP3A37的开放阅读框为1512 bp，预测该蛋白质有504个氨基酸，与鸡CYP3A37的同源性为97%。火鸡基因由13个外显子和12个内含子组成。第11个内含子中的一个单核苷酸多态性被用于将CYP3A37定位到火鸡连锁群10（对应鸡的14号染色体，GGA14）。由于P450在火鸡对AFB1毒性极度敏感中发挥重要作用，本研究将有助于鉴定家禽中这一重要基因的等位基因变体。
