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中枢神经系统中磷酸吡哆醛的调节与功能

Regulation and function of pyridoxal phosphate in CNS.

作者信息

Ebadi M

机构信息

Department of Pharmacology, University of Nebraska, College of Medicine, 42nd Street and Dewey Avenue, Omaha, Nebraska 68105, USA.

出版信息

Neurochem Int. 1981;3(3-4):181-205. doi: 10.1016/0197-0186(81)90001-2.

Abstract

Pyridoxal phosphate and pyridoxamine phosphate, the catalytically active forms of vitamin B(6), influence brain function by participating at stages in metabolism of proteins, lipids, carbohydrates, other coenzymes and hormones. Vitamin B(6) participates in the metabolism of amino acids in the form of decarboxylation, transamination, deamination, racemization and desulfhydration reactions. The crucial roles that these coenzymes play in the maintenance of functional integrity of the brain become evident when one realizes that some compounds implicated as neurotransmitters are synthesized and/or metabolized by the aid of the vitamin B(6)-dependent enzymatic reactions. These include dopamine, norepinephrine and serotonin, tyramine, tryptamine, taurine, histamine, gamma aminobutyric acid, and even acetylcholine indirectly. In recent years, the above-mentioned biogenic amines have become of considerable interest to neurobiologists who are investigating the etiology and the pathological manifestations of many disorders of the central nervous system such as Parkinsonism, Huntington's chorea, minimal brain disfunction, schizophrenia, depression, sleep disorders and seizure disorders. Vitamin B(6) deficiency in these cases is characterized by anemia, growth retardation and alteration in neuronal function, including neuropathies, hyperirritability, hyperexcitability and convulsions. The importance of vitamin B(6) in the study of brain function assumes still greater significance when one considers the effects of nutritional deficiencies on growth and development of the brain and mental processes and in the involvement of vitamin B(6) in some inborn errors of metabolism which result in mental retardation. Vitamin B(6) deficiency results in a lowered concentration of Coenzyme A in blood, in reduced absorption and storage of vitamin B(12), and in increased excretion of vitamin C. Furthermore, vitamin B(6) acts synergistically with vitamin E to control metabolism of unsaturated fats, with vitamin C in tyrosine metabolism and with niacin in its action and participates in niacin synthesis. In addition, vitamin B(6) deficiency results in insufficiency of insulin and in alteration of the functions of adrenal and pituitary glands, since it is involved in the synthesis of growth hormone, follicle-stimulating hormone, luteinizing hormone, aldosterone, glucagon, cortisol, estradiol, testosterone and epinephrine. It is hoped that by understanding the factors that regulate the synthesis, binding, storage and degradation of pyridoxal phosphate in the brain, a better insight into the role of vitamin B(6) in neurobiology may be gained.

摘要

磷酸吡哆醛和磷酸吡哆胺是维生素B6的催化活性形式,它们通过参与蛋白质、脂质、碳水化合物、其他辅酶和激素的代谢过程来影响脑功能。维生素B6以脱羧、转氨、脱氨、消旋和脱硫反应的形式参与氨基酸的代谢。当人们认识到一些被认为是神经递质的化合物是借助维生素B6依赖性酶促反应合成和/或代谢时,这些辅酶在维持大脑功能完整性中所起的关键作用就变得显而易见了。这些神经递质包括多巴胺、去甲肾上腺素和5-羟色胺、酪胺、色胺、牛磺酸、组胺、γ-氨基丁酸,甚至间接包括乙酰胆碱。近年来,上述生物胺引起了神经生物学家的极大兴趣,他们正在研究许多中枢神经系统疾病如帕金森病、亨廷顿舞蹈病、轻微脑功能障碍、精神分裂症、抑郁症、睡眠障碍和癫痫症的病因及病理表现。在这些情况下,维生素B6缺乏的特征是贫血、生长发育迟缓以及神经元功能改变,包括神经病变、过敏症、过度兴奋和惊厥。当考虑到营养缺乏对大脑生长发育和心理过程的影响以及维生素B6参与某些导致智力迟钝的先天性代谢错误时,维生素B6在脑功能研究中的重要性就显得更加突出。维生素B6缺乏会导致血液中辅酶A浓度降低、维生素B12的吸收和储存减少以及维生素C排泄增加。此外,维生素B6与维生素E协同作用以控制不饱和脂肪的代谢,与维生素C协同参与酪氨酸代谢,与烟酸协同发挥作用并参与烟酸的合成。另外,维生素B6缺乏会导致胰岛素分泌不足以及肾上腺和垂体功能改变,因为它参与生长激素、促卵泡激素、促黄体生成素、醛固酮、胰高血糖素、皮质醇、雌二醇、睾酮和肾上腺素的合成。希望通过了解调节大脑中磷酸吡哆醛的合成、结合、储存和降解的因素,可以更好地洞察维生素B6在神经生物学中的作用。

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