Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively). Does not phosphorylate N-acetyl-D-glucosamine (By similarity). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan. When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331). ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+) ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+) ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+) ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+) ATP + D-glucosamine = ADP + D-glucosamine 6-phosphate + H(+) Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate. Hexokinase activity is inhibited by N-acetyl-D-glucosamine. Carbohydrate metabolism; hexose metabolism. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4. Monomer (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity). Interacts (via N-terminal spermatogenic cell-specific region) with PFKM isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946). The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (By similarity). Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331). Isoform HK1-SC is an integral membrane protein. In rapidly growing tumor cells exhibiting high glucose catabolic rates, isoform HK1 is markedly elevated. Isoform HK1-SA, isoform HK1-SB and isoform HK1-SC are found only in spermatogenic cells. Isoform HK1-SC is detected in round spermatids, condensing spermatids and mature sperm where it is found in the head membranes, mitochondria of the midpiece and the fibrous sheath of the flagellum. Expressed within the principal piece and midpiece of sperm tail (at protein level). Isoform HK1-SA: First expressed during meiosis and continues to be present in postmeiotic germ cells (PubMed:8396993, PubMed:9450953). Isoform HK1-SB: Present only in postmeiotic germ cells (PubMed:8396993). The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule. Tyrosine-phosphorylated. Produced by alternative splicing and alternative initiation at Met-53 of isoform HK1-SA. Produced by alternative initiation at Met-53 of isoform HK1-SA. Belongs to the hexokinase family.