PANK

Pantothenate kinase (PanK) catalyzes the reaction between pantothenate (vitamin B5) and ATP to produce 4'-phosphopantothenate, the first step in the synthesis of coenzyme A (CoA). CoA plays a critical role in numerous metabolic processes, such as the synthesis and oxidation of fatty acids, complex lipid synthesis, and the oxidation of pyruvate in the citric acid cycle.
In mammals, there are four active isoforms of pantothenate kinase: PanK1α, PanK1β, PanK2, and PanK3, encoded by three different genes. Each isoform has distinct sensitivities to feedback inhibition by acetyl-CoA and is localized in different cellular compartments. For instance, PanK1α is primarily located in the nucleus, while PanK2 is mainly found in the intermembrane space of mitochondria. This specific subcellular localization allows pantothenate kinase to sense and regulate CoA levels in various cellular environments, thereby influencing critical energy metabolic pathways such as fatty acid oxidation and gluconeogenesis.
The expression and activity of pantothenate kinase are closely linked to CoA levels, affecting the body's metabolic regulation capabilities. Dysfunctions in pantothenate kinase can lead to metabolic diseases and neurodegenerative disorders. For example, Pank1 knockout mice exhibit impaired gluconeogenesis during fasting, and Pank2 knockout mice show infertility and motor dysfunctions. Additionally, PanK2 is associated with functional deficits in neurodegeneration and brain iron accumulation disease (NBIA)^[1].

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