BIOSYNTHESIS AND METABOLISM OF RETINOIC ACID - ROLES OF CRBP AND CRABP IN RETINOIC ACID - ROLES OF CRBP AND CRABP IN RETINOIC ACID HOMEOSTASIS
BIOSYNTHESIS AND METABOLISM OF RETINOIC ACID - ROLES OF CRBP AND CRABP IN RETINOIC ACID - ROLES OF CRBP AND CRABP IN RETINOIC ACID HOMEOSTASIS
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DOI：
10.1093/jn/123.suppl_2.362
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发表时间：
1993-02-01
影响因子：
4.2
通讯作者：
NAPOLI, JL
中科院分区：
文献类型：
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作者：
NAPOLI, JL
构成视黄酸生物合成和代谢途径的酶可以识别视黄酸结合蛋白作为效应物和底物。脱细胞视黄醇结合蛋白（CRBP）刺激胆汁盐非依赖性膜结合视黄酯水解酶，导致内源性视黄酯水解和holoCRBP的形成。HoloCRBP将视黄醇递送到微粒体烟酰胺腺嘌呤二核苷酸磷酸依赖性脱氢酶，保护其免受人为氧化，并拒绝不能识别结合蛋白的酶进入视黄醇。通过CRBP可将合成的视黄醇从微粒体转移到胞质溶胶中。已经纯化了一种胞质视网膜脱氢酶，其在CRBP存在下从微粒体产生的视网膜和从复合物CRBP-视网膜本身产生视黄酸。因此，CRBP（I型）似乎通过一系列蛋白质-蛋白质相互作用引导类维生素A通过视黄酸合成反应。细胞视黄酸结合蛋白（I型）通过螯合视黄酸并作为低Km底物促进视黄酸代谢，从而也调节视黄酸的稳态浓度。
The enzymes that constitute the pathway of retinoic acid biosynthesis and metabolism may recognize retinoid binding proteins as effectors and substrates. Apocellular retinol-binding protein (CRBP) stimulates a bile-salt independent membrane-bound retinyl ester hydrolase resulting in the hydrolysis of endogenous retinyl esters and the formation of holoCRBP. HoloCRBP delivers retinol to a microsomal nicotinamide-adenine dinucleotide phosphate-dependent dehydrogenase, protects it from artifactual oxidation and denies enzymes that cannot recognize the binding protein access to retinol. The retinal synthesized may be transferred from the microsomes to the cytosol by CRBP. A cytosolic retinal dehydrogenase has been purified that produces retinoic acid from retinal generated by microsomes in the presence of CRBP and from the complex CRBP-retinal itself. Thus, CRBP(type I) seems to channel retinoids through the reactions of retinoic acid synthesis via a series of protein-protein interactions. Cellular retinoic acid-binding protein (type I) facilitates retinoic acid metabolism by sequestering it and by acting as a low Km substrate, thereby also modulating the steady-state concentrations of retinoic acid.