Bass N M
Department of Medicine, University of California, San Francisco 94143-0538.
Mol Cell Biochem. 1993;123(1-2):191-202. doi: 10.1007/BF01076492.
The cellular fatty acid-binding proteins (FABP) and cellular retinoid (retinol, retinoic acid)-binding proteins (CRtBP) are structurally and functionally-defined groups within an evolutionarily conserved gene family. CRtBP are expressed in both fully differentiated and developing tissues in a manner that supports a relationship to the action of retinoic acid in morphogenesis and cellular differentiation. The FABP are, by contrast, expressed only in fully differentiated tissues in a manner compatible with a major function in the metabolism of long-chain fatty acids (LCFA) for energy production or storage. The precise function(s) of FABP and CRtBP remain imperfectly understood, while subspecialization of function(s) within the two groups is suggested by the complex diversity in both of structurally distinct members that display striking tissue and temporal specificity of expression in addition to ligand specificity. Notwithstanding this considerable apparent functional diversity among the FABP and CRtBP, available evidence supports a dual set of generic functions for both protein groups in a) promoting cellular flux of poorly water-soluble ligands and their subsequent metabolic utilization or transformation, and b) sequestration of ligands in a manner that limits their association with alternative binding sites within the cell, of which members of the steroid hormone nuclear receptor superfamily (HNR) are a potentially important category. Theoretical as well as experimental models probing diffusional fluxes of LCFA in vitro and in living cells have provided support for a function for FABP in intracellular LCFA transport. Protein-bound ligand also appears to provide the substrate for metabolic transformation of retinoids bound to CRtBP, but convincing evidence is lacking for an analogous mechanism in the direct facilitation of fatty acid utilization by FABP. An emerging relationship between FABP and CRtBP function centers on their binding of, and induction by, ligands which activate or transform specific HNR-the retinoic acid receptors and the peroxisome proliferator activated receptor in the case of CRtBP and FABP, respectively. Evidence consistent with both a 'promotive' role (provision of ligands for HNR) and a 'protective' role (limiting availability of free ligand for HNR association) has been advanced for CRtBP. Available data supports a 'protective' function for cellular retinoic acid-binding proteins (CRABP) and liver FABP (L-FABP) and points to the existence of ligand-defined, lipid-binding-protein-HNR relationships in which CRABP serve to attenuate the induction of gene expression by retinoic acid, and in which L-FABP may modulate a cellular adaptive multigene response to increased LCFA flux or compromised LCFA utilization.(ABSTRACT TRUNCATED AT 400 WORDS)
细胞脂肪酸结合蛋白（FABP）和细胞类视黄醇（视黄醇、视黄酸）结合蛋白（CRtBP）是进化上保守的基因家族中在结构和功能上有明确界定的类别。CRtBP在完全分化和发育中的组织中均有表达，其表达方式表明它与视黄酸在形态发生和细胞分化中的作用有关。相比之下，FABP仅在完全分化的组织中表达，其表达方式与长链脂肪酸（LCFA）代谢以产生或储存能量的主要功能相一致。FABP和CRtBP的确切功能仍未完全明了，而两组蛋白功能的亚专业化则由结构上不同成员的复杂多样性所暗示，这些成员除了具有配体特异性外，还表现出显著的组织和时间表达特异性。尽管FABP和CRtBP之间存在明显的功能多样性，但现有证据支持这两类蛋白具有双重通用功能：a）促进水溶性差的配体的细胞通量及其随后的代谢利用或转化；b）以限制配体与细胞内其他结合位点结合的方式隔离配体，类固醇激素核受体超家族（HNR）成员就是一个潜在的重要类别。探究体外和活细胞中LCFA扩散通量的理论及实验模型为FABP在细胞内LCFA转运中的功能提供了支持。与蛋白结合的配体似乎也为与CRtBP结合的类视黄醇的代谢转化提供了底物，但缺乏令人信服的证据证明FABP直接促进脂肪酸利用存在类似机制。FABP和CRtBP功能之间新出现的关系集中在它们与激活或转化特定HNR的配体的结合及受其诱导上，对于CRtBP和FABP而言，分别是视黄酸受体和过氧化物酶体增殖物激活受体。对于CRtBP，已提出了与“促进”作用（为HNR提供配体）和“保护”作用（限制游离配体与HNR结合的可用性）一致的证据。现有数据支持细胞视黄酸结合蛋白（CRABP）和肝脏FABP（L-FABP）具有“保护”功能，并指出存在由配体定义的脂质结合蛋白-HNR关系，其中CRABP可减弱视黄酸对基因表达的诱导，而L-FABP可能调节细胞对增加的LCFA通量或受损的LCFA利用的适应性多基因反应。（摘要截选至400字）
