Developmental expression of cytochrome CYP26B1 (P450RAI-2) in human cephalic tissues.

Expression levels of cytochrome CYP26B1, which is involved in the specific all-trans-RA inactivation, were evaluated in human cephalic tissues at gestational days 57-110 and exhibited values approximately 10-fold higher than later gestational days 112-224 and adult tissues. CYP26B1 mRNA levels in the adult cerebellum were approximately 2-fold higher than in the adult whole brain tissue. Considered together, these data suggest a unique role for CYP26B1 during human brain development.

Enzymic catalysis of the accumulation of acetaldehyde from ethanol in human prenatal cephalic tissues: evaluation of the relative contributions of CYP2E1, alcohol dehydrogenase, and catalase/peroxidases.

Background: The human prenatal brain is very sensitive to the toxic effects of ethanol, but very little information is available concerning the conversion of ethanol to the highly cytotoxic metabolite, acetaldehyde, in that organ. Thus, experiments were designed to investigate rates of accumulation of acetaldehyde from ethanol in the prenatal human brain.

Methods: Prenatal human cephalic tissue homogenates were used as enzyme sources and were compared with analogous preparations of adult rat livers.

Catalysis of the 4-hydroxylation of retinoic acids by cyp3a7 in human fetal hepatic tissues.

Cytochrome P4503A7 (CYP3A7) is the primary CYP isoform expressed in human fetal hepatic microsomes, and its potential role in human embryotoxicity has attracted considerable investigative attention. In this study, we investigated the 4-hydroxylation of highly embryotoxic and teratogenic retinoic acids (RA) as catalyzed by human fetal liver microsomes (HFLM) and demonstrated that CYP3A7 is an efficient RA hydroxylase. When all-trans-retinoic acid (tRA), 9-cis-retinoic acid (9cRA), or 13-cis-retinoic acid (13cRA) were incubated with HFLM (54-109 gestational days) plus NADPH, each of these three retinoic acids was rapidly converted to its corresponding 4-hydroxy and 4-oxo metabolites.

Patterns of CYP26 expression in human prenatal cephalic and hepatic tissues indicate an important role during early brain development.

CYP26 (P450RAI) catalyzes catabolic retinoic acid (RA) hydroxylation and thereby appears to play a critical role in retinoid signaling pathways during development. In this study, a quantitative competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed for evaluation of CYP26 message levels in human prenatal tissues. Statistical analyses of transcription levels in 12 prenatal human brains and six prenatal human livers demonstrated good sensitivity and reproducibility.

Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis of all-trans-retinol oxidation by human P-450 cytochromes.

Oxidative conversion of all-trans-retinol (t-ROH) to all-trans-retinal (t-RAL) is recognized as the rate-limiting step for biosynthesis of all-trans-retinoic acid from t-ROH in mammalian hepatic tissues. The purpose of this study was to investigate the role of human cytochrome P-450 (CYP)-dependent monooxygenation in the conversion of t-ROH to t-RAL. Adult human liver microsomes (HLMS) were incubated with t-ROH, and retinoids generated were identified and quantified by liquid chromatography-mass spectroscopy, HPLC, and other methods.