کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1178024 962658 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Vitamin B6 salvage enzymes: Mechanism, structure and regulation
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Vitamin B6 salvage enzymes: Mechanism, structure and regulation
چکیده انگلیسی

Vitamin B6 is a generic term referring to pyridoxine, pyridoxamine, pyridoxal and their related phosphorylated forms. Pyridoxal 5′-phosphate is the catalytically active form of vitamin B6, and acts as cofactor in more than 140 different enzyme reactions. In animals, pyridoxal 5′-phosphate is recycled from food and from degraded B6-enzymes in a “salvage pathway”, which essentially involves two ubiquitous enzymes: an ATP-dependent pyridoxal kinase and an FMN-dependent pyridoxine 5′-phosphate oxidase. Once it is made, pyridoxal 5′-phosphate is targeted to the dozens of different apo-B6 enzymes that are being synthesized in the cell. The mechanism and regulation of the salvage pathway and the mechanism of addition of pyridoxal 5′-phosphate to the apo-B6-enzymes are poorly understood and represent a very challenging research field. Pyridoxal kinase and pyridoxine 5′-phosphate oxidase play kinetic roles in regulating the level of pyridoxal 5′-phosphate formation. Deficiency of pyridoxal 5′-phosphate due to inborn defects of these enzymes seems to be involved in several neurological pathologies. In addition, inhibition of pyridoxal kinase activity by several pharmaceutical and natural compounds is known to lead to pyridoxal 5′-phosphate deficiency. Understanding the exact role of vitamin B6 in these pathologies requires a better knowledge on the metabolism and homeostasis of the vitamin. This article summarizes the current knowledge on structural, kinetic and regulation features of the two enzymes involved in the PLP salvage pathway. We also discuss the proposal that newly formed PLP may be transferred from either enzyme to apo-B6-enzymes by direct channeling, an efficient, exclusive, and protected means of delivery of the highly reactive PLP. This new perspective may lead to novel and interesting findings, as well as serve as a model system for the study of macromolecular channeling. This article is part of a Special Issue entitled: Pyridoxal Phosphate Enzymology.

Research Highlights
► In animals, PLP is recycled from food and degraded B6-enzymes in a salvage pathway.
► Two enzymes in this pathway: pyridoxal kinase and pyridoxine 5'-phosphate oxidase.
► Inborn defects of these enzymes are involved in neurological pathologies.
► Regulation mechanism of the salvage pathway enzymes.
► Channeling mechanism for the addition of PLP to apo-B6-enzymes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1814, Issue 11, November 2011, Pages 1597–1608
نویسندگان
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