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组氨酸脱羧酶与芳香族L-氨基酸脱羧酶分子网络之间的结构和功能类比及差异:生物医学意义

Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks: Biomedical implications.

作者信息

Sanchez-Jiménez Francisca, Pino-Ángeles Almudena, Rodríguez-López Rocio, Morales María, Urdiales José Luis

机构信息

Departamento de Biología Molecular y Bioquímica. Facultad de Ciencias, Universidad de Málaga, Spain; Centro de Investigación en red en Enfermedades Raras (ISCIII), 29071 Málaga, Spain.

Department of Chemistry, The City College of New York, New York, NY 10031, USA.

出版信息

Pharmacol Res. 2016 Dec;114:90-102. doi: 10.1016/j.phrs.2016.08.032. Epub 2016 Oct 18.

Abstract

Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. The enzymes share many structural and functional analogies, while their product metabolisms also follow similar patterns that are confluent in some metabolic steps. They are involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. As a consequence, metabolic elements of both BA subfamilies are also co-participants in a long list of human diseases. This review summarizes the analogies and differences in their origin (HDC and DDC) as well as their common pathophysiological scenarios. The major gaps of information are also underlined, as they delay the possibility of holistic approaches that would help personalized medicine and pharmacological initiatives for prevalent and rare diseases.

摘要

人类组氨酸脱羧酶(HDC)和多巴脱羧酶(DDC)是高度同源的酶,分别负责生物胺(BA)如组胺、5-羟色胺和多巴胺的合成。这两种酶具有许多结构和功能上的相似性,同时它们的产物代谢也遵循相似模式,在某些代谢步骤中相互融合。它们参与共同的生理功能,如神经传递、胃肠道功能、免疫、细胞生长和细胞分化。因此,两个生物胺亚家族的代谢成分也共同参与了众多人类疾病。本综述总结了它们(HDC和DDC)起源方面的异同以及常见的病理生理情况。还强调了主要的信息空白,因为这些空白延缓了采用整体方法的可能性,而整体方法有助于针对常见和罕见疾病开展个性化医疗和药理研究。

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