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Zebrafish Cyp26a1 oxidizes all-trans retinoic acid in microsome assays to 4-OH-RA and 4-oxo-RA, the canonical CYP26A1 reaction products.
"Zebrafish Cyp26a1 catalyzes oxidative metabolism of atRA, generating metabolites dominated by **4-hydroxy-RA (4-OH-RA)** and **4-oxo-RA (4-oxo-RA)** in microsome assays from transfected cells
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4-hydroxylation is the primary transformation for CYP26A1, with additional products including 18-hydroxy-RA and more polar secondary metabolites.
"Reviews of CYP26A1 metabolism emphasize **4-hydroxylation as the primary transformation** for CYP26A1 (and CYP26B1), with additional products such as **18-hydroxy-RA** and more polar secondary metabolites
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Zebrafish CYP26 enzymes act on retinoic acid isomers but do not metabolize retinol or retinal, indicating specialization for retinoic acid rather than upstream retinoids.
"Cell/microsome assays of zebrafish CYP26 family members show activity toward **RA isomers** (atRA, 9-cis RA, 13-cis RA) and **no detectable metabolism of retinol or retinal** under the tested conditions, supporting specialization for RA
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Cyp26a1 is a membrane-anchored microsomal (ER) cytochrome P450 with a heme center, requiring electrons from NADPH via cytochrome P450 oxidoreductase (POR).
"CYP26 enzymes are described as **membrane-anchored microsomal (endoplasmic reticulum, ER) cytochrome P450s** with a heme center and class II P450 electron-transfer architecture: each catalytic cycle requires electrons supplied from **NADPH via cytochrome P450 oxidoreductase (POR)**, which uses **FAD and FMN** cofactors
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CYP26 enzymes are high-efficiency retinoic-acid clearance enzymes (reported Km < 100 nM in transfected-cell systems) that control RA homeostasis.
"A review summarizing CYP26 biochemical studies reports **high catalytic activity** for atRA, including **Km < 100 nM** (in COS-1 transfected cell systems) and **turnover ~1–10 pmol/min/pmol**
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cyp26a1 and its paralogs cyp26b1/cyp26c1 act redundantly to shape the retinoic-acid response pattern needed for zebrafish hindbrain development; their depletion expands RA-responsive gene expression across the hindbrain.
"Hernandez et al. (2007; published Jan 2007; https://doi.org/10.1242/dev.02706) demonstrate that zebrafish orthologs of mammalian CYP26 genes (**cyp26a1, cyp26b1, cyp26c1**) act **redundantly** to shape the RA response pattern necessary for hindbrain development
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cyp26a1 expression in anterior neural ectoderm, forebrain, midbrain, anterior hindbrain, and tailbud establishes anterior RA-depleted domains opposing posterior aldh1a2/raldh2-driven RA synthesis.
"cyp26a1 is expressed early in presumptive anterior neural ectoderm, and later in forebrain, midbrain, anterior hindbrain, and tailbud territories, contributing to establishment of anterior RA-depleted domains opposing posterior RA synthesis and shaping the rostrocaudal RA signaling landscape
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cyp26a1 is under complex RA- and Fgf-driven feedback/feedforward control, conferring robustness of the embryonic RA gradient.
"cyp26a1 is under complex feedback and feedforward control by RA and Fgf signaling
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Overexpression of cyp26a1 mRNA reduces endogenous RA activity and produces reduced-RA phenotypes, confirming a functional role in RA clearance.
"microinjection of cyp26a1 mRNA reduces endogenous RA activity and yields phenotypes resembling reduced-RA conditions, consistent with a role in RA clearance
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The primary molecular function of zebrafish Cyp26a1 is as an ER/microsomal cytochrome P450 that hydroxylates/oxidizes retinoic acid, reducing RA signaling capacity.
"ER/microsomal cytochrome P450 enzyme that **hydroxylates/oxidizes retinoic acid**, producing **4-OH-RA and 4-oxo-RA** (major products), thereby reducing RA signaling capacity
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