Write a 100-350 word essay about the enzyme human GNE. Provide information related to enzyme: i) function, ii) reaction pathways, ii) Location, and iv) diseases. In writing include these four subheadings

### Function
Human GNE, or glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase, is a bifunctional enzyme that plays a critical role in the biosynthesis of sialic acids. GNE catalyzes the first two steps in this pathway: it converts UDP-N-acetylglucosamine (UDP-GlcNAc) to N-acetylmannosamine (ManNAc) through its epimerase activity and then phosphorylates ManNAc to produce ManNAc-6-phosphate through its kinase activity. Sialic acids, the end products of this pathway, are essential for cellular functions, including cell-cell interactions, immune response, and protein stability.

### Reaction Pathways
GNE is central to the sialic acid biosynthesis pathway. The enzyme first epimerizes UDP-GlcNAc to produce ManNAc, which is subsequently phosphorylated to ManNAc-6-phosphate. This molecule is then further converted to N-acetylneuraminic acid (Neu5Ac), the most common form of sialic acid. Sialic acids are then activated to CMP-sialic acid, which is used in the glycosylation of proteins and lipids, forming sialoglycoconjugates that are crucial for many biological processes, including the regulation of immune responses and cell signaling.

### Location
GNE is predominantly localized in the cytoplasm, where it interacts with its substrates to initiate the sialic acid biosynthesis pathway. The cytoplasmic localization allows GNE to efficiently catalyze the early steps of sialic acid production, ensuring a steady supply of this important molecule for glycosylation processes in the Golgi apparatus and other cellular compartments.

### Diseases
Mutations in the GNE gene are associated with a rare neuromuscular disorder known as GNE myopathy, also known as hereditary inclusion body myopathy (HIBM). This condition is characterized by progressive muscle weakness and atrophy, particularly in the distal muscles. The disease results from impaired sialic acid biosynthesis due to defective GNE enzyme activity, leading to reduced sialylation of glycoproteins, which affects muscle function. In addition to GNE myopathy, altered GNE activity has been implicated in other disorders related to sialic acid metabolism, highlighting the enzyme’s critical role in maintaining cellular and systemic homeostasis.