| Gene Symbol | HK1 | |---|---| | Full Name | Hexokinase 1 | | Chromosomal Location | 10p11.2 | | NCBI Gene ID | [3099](https://www.ncbi.nlm.nih.gov/gene/3099) | | OMIM | [142600](https://www.omim.org/entry/142600) | | Ensembl ID | ENSG00000156515 | | UniProt ID | [P19367](https://www.uniprot.org/uniprot/P19367) | | Associated Diseases | Hexokinase Deficiency, Alzheimer's Disease, Parkinson's Disease |
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Overview
Mermaid diagram (expand to render)
Hexokinase 1 (HK1) is a fundamental metabolic enzyme that catalyzes the first committed step in glycolysis: the phosphorylation of glucose to glucose-6-phosphate using ATP.[@gulshan2019] This reaction is rate-limiting and essential for cellular energy production, particularly in high-energy-demand tissues such as the brain. HK1 is one of four hexokinase isoforms (HK1-HK4) in humans, with HK1 being the predominant isoform in [neurons](/entities/neurons).[@wilson2020] Beyond its canonical metabolic function, HK1 has attracted significant attention in neurodegeneration research due to its unique mitochondrial binding properties and altered activity in both Alzheimer's disease (AD) and Parkinson's disease (PD).[@roberts2021][@cheng2020]
In the nervous system, HK1 plays a critical role in maintaining neuronal energy homeostasis. Unlike other hexokinases, HK1 possesses an N-terminal mitochondrial-binding domain that allows it to associate with the voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane. This direct coupling to mitochondrial ATP production provides neurons with a metabolic advantage, particularly in regions with high synaptic activity such as the [hippocampus](/brain-regions/hippocampus) and cerebral [cortex](/brain-regions/cortex).[@wilson2020] Disruption of this mitochondrial HK1-VDAC interaction has been implicated in the pathogenesis of multiple neurodegenerative diseases.[@roberts2021]
Function
Hexokinase 1 (HK1) is the first enzyme in glycolysis, catalyzing the phosphorylation of glucose to glucose-6-phosphate using ATP. This is a rate-limiting step in glucose metabolism.
[Gulshan et al., Hexokinase 1 dysfunction in Alzheimer's disease. Neurobiology of Aging (2019) (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.02.021)
[Roberts et al., Targeting hexokinase in neurodegeneration. Trends in Pharmacological Sciences (2021) (2021)](https://doi.org/10.1016/j.tips.2021.05.004)
[Cheng et al., HK1 and mitochondrial dysfunction in PD. Movement Disorders (2020) (2020)](https://doi.org/10.1002/mds.28012)
Pathway Diagram
The following diagram shows the key molecular relationships involving HK1 — Hexokinase 1 discovered through SciDEX knowledge graph analysis: