A novel cytochrome P450 expressed primarily in brain.
hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7 alpha-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroid-metabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.
Stapleton
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G
Centre for Genome Research, University of Edinburgh, United Kingdom.
Steel
M
M
Richardson
M
M
Mason
J O
JO
Rose
K A
KA
Morris
R G
RG
Lathe
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain / Q000201:enzymology*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000737:chemistry; D003337:Corpus Callosum / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000072474:Cytochrome P450 Family 7; D018076:DNA, Complementary; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D017386:Sequence Homology, Amino Acid; D012727:Sex Characteristics; D013250:Steroid Hydroxylases; D013379:Substrate Specificity; D014158:Transcription, Genetic
D018076:DNA, Complementary; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; D000072474:Cytochrome P450 Family 7; C097207:Cyp7b1 protein, mouse; C490784:Cyp7b1 protein, rat