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• W2051897400 endingPage "1608" @default.
• W2051897400 startingPage "1597" @default.
• W2051897400 abstract "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." @default.
• W2051897400 created "2016-06-24" @default.
• W2051897400 creator A5015890126 @default.
• W2051897400 creator A5028033960 @default.
• W2051897400 creator A5075305488 @default.
• W2051897400 date "2011-11-01" @default.
• W2051897400 modified "2023-10-09" @default.
• W2051897400 title "Vitamin B6 salvage enzymes: Mechanism, structure and regulation" @default.
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