Further characterization of RLM2 and comparison with a related form of cytochrome P-450, RLM2b.
Further characterization of RLM2 and comparison with a related form of cytochrome P-450, RLM2b.
复制标题
RLM2 的进一步表征以及与细胞色素 P-450 的相关形式 RLM2b 的比较。
DOI：
10.1016/0003-9861(88)90264-0
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发表时间：
1988
影响因子：
3.9
通讯作者：
Schenkman,JB
中科院分区：
文献类型：
--
作者：
Thummel,KE;Favreau,LV;Mole,JE;Schenkman,JB
We have extended the characterization of RLM2, a constitutive form of rat liver cytochromeP-450, using immunochemical means to quantitate its presence in microsomes, to follow its development in maturing male and female rats, and to determine its response to prototypicalP-450 inducers. In addition, RLM2 is compared to RLM2b, a form ofP-450 with similar migration on SDS-PAGE and NH2-terminal amino acid sequence. RLM2b is expressed in both sexes at a level of 0.08 nmol/mg microsomal protein at 2 weeks of age. In female rats, this level is unchanged with maturation. However, in the male, the level declined with maturation to reach 0.02 nmol/mg protein by 12 weeks of age. RLM2 is a male-specific form of cytochromeP-450. Originally absent in the 2-week-old rat, it reached a level of 0.03 nmol/mg protein in the adult male, its appearance and increase coinciding with the onset of puberty. Both phenobarbital and 3-methylcholanthrene induced microsomal levels of RLM2b in the adult male and female rat. RLM2, however, was suppressed in the male rat, 58 and 42%, respectively, by the same treatments. RLM2b and RLM2 each catalyze a unique spectrum of hydroxytestosterone metabolites. RLM2b is highly site specific. In contrast, RLM2 produces several isomeric products in the same region of the testosterone molecule. Substitution of the acetyl group of progesterone for the 17-hydroxy group of testosterone did not alter the site specificity of RLM2b, but did alter it for RLM2, indicating, further, a difference in the active site conformation of the two enzymes. Although RLM2b and RLM2 responded differently to inducers and to a changing physiology during maturation, and were functionally quite distinct, the proteins showed a high degree of immunologic relatedness which is suggestive of significant structural similarities. Structural differences do exist, however, as α-chymotryptic digestion formed a number of peptide fragments that differed between the two proteins.
