Hexokinase I

Last updated
HK1
Protein HK1 PDB 1bg3.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HK1 , HK1-ta, HK1-tb, HK1-tc, HKD, HKI, HMSNR, HXK1, hexokinase 1, HK, hexokinase, RP79, NEDVIBA
External IDs OMIM: 142600; MGI: 96103; HomoloGene: 100530; GeneCards: HK1; OMA:HK1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001146100
NM_010438

RefSeq (protein)

NP_001139572
NP_034568

Location (UCSC) Chr 10: 69.27 – 69.4 Mb Chr 10: 62.1 – 62.22 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Hexokinase I, also known as hexokinase A and HK1, is an enzyme that in humans is encoded by the HK1 gene on chromosome 10. Hexokinases phosphorylate glucose to produce glucose-6-phosphate (G6P), the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in five transcript variants which encode different isoforms, some of which are tissue-specific. Each isoform has a distinct N-terminus; the remainder of the protein is identical among all the isoforms. A sixth transcript variant has been described, but due to the presence of several stop codons, it is not thought to encode a protein. [provided by RefSeq, Apr 2009] [5]

Structure

Hexokinase I is one of four highly homologous hexokinase isoforms in mammalian cells. [6] [7]

Gene

The HK1 gene spans approximately 131 kb and consists of 25 exons. Alternative splicing of its 5’ exons produces different transcripts in different cell types: exons 1-5 and exon 8 (exons T1-6) are testis-specific exons; exon 6, located approximately 15 kb downstream of the testis-specific exons, is the erythroid-specific exon (exon R); and exon 7, located approximately 2.85 kb downstream of exon R, is the first 5’ exon for the ubiquitously expressed hexokinase I isoform. Moreover, exon 7 encodes the porin-binding domain (PBD) conserved in mammalian HK1 genes. Meanwhile, the remaining 17 exons are shared among all hexokinase I isoforms.

In addition to exon R, a stretch of the proximal promoter that contains a GATA element, an SP1 site, CCAAT, and an Ets-binding motif is necessary for expression of HK-R in erythroid cells. [6]

Protein

This gene encodes a 100 kDa homodimer with a regulatory N-terminal domain (1-475), catalytic C-terminal domain (residues 476-917), and an α-helix connecting its two subunits. [6] [8] [9] [10] Both terminal domains are composed of a large subdomain and a small subdomain. The flexible region of the C-terminal large subdomain (residues 766–810) can adopt various positions and is proposed to interact with the base of ATP. Moreover, glucose and G6P bind in close proximity at the N- and C-terminal domains and stabilize a common conformational state of the C-terminal domain. [8] [9] According to one model, G6P acts as an allosteric inhibitor which binds the N-terminal domain to stabilize its closed conformation, which then stabilizes a conformation of the C-terminal flexible subdomain that blocks ATP. A second model posits that G6P acts as an active inhibitor that stabilizes the closed conformation and competes with ATP for the C-terminal binding site. [8] Results from several studies suggest that the C-terminal is capable of both catalytic and regulatory action. [11] Meanwhile, the hydrophobic N-terminal lacks enzymatic activity by itself but contains the G6P regulatory site and the PBD, which is responsible for the protein's stability and binding to the outer mitochondrial membrane (OMM). [6] [12] [10] [13]

Function

As one of two mitochondrial isoforms of hexokinase and a member of the sugar kinase family, hexokinase I catalyzes the rate-limiting and first obligatory step of glucose metabolism, which is the ATP-dependent phosphorylation of glucose to G6P. [8] [7] [10] [14] Physiological levels of G6P can regulate this process by inhibiting hexokinase I as negative feedback, though inorganic phosphate (Pi) can relieve G6P inhibition. [8] [12] [10] However, unlike HK2 and HK3, hexokinase I itself is not directly regulated by Pi, which better suits its ubiquitous catabolic role. [7] By phosphorylating glucose, hexokinase I effectively prevents glucose from leaving the cell and, thus, commits glucose to energy metabolism. [8] [13] [12] [10] Moreover, its localization and attachment to the OMM promotes the coupling of glycolysis to mitochondrial oxidative phosphorylation, which greatly enhances ATP production by direct recycling of mitochondrial ATP/ADP to meet the cell's energy demands. [14] [10] [15] Specifically, OMM-bound hexokinase I binds VDAC1 to trigger opening of the mitochondrial permeability transition pore and release mitochondrial ATP to further fuel the glycolytic process. [10] [7]

Another critical function for OMM-bound hexokinase I is cell survival and protection against oxidative damage. [14] [7] Activation of Akt kinase is mediated by hexokinase I-VDAC1 coupling as part of the growth factor-mediated phosphatidyl inositol 3-kinase (PI3)/Akt cell survival intracellular signaling pathway, thus preventing cytochrome c release and subsequent apoptosis. [14] [6] [10] [7] In fact, there is evidence that VDAC binding by the anti-apoptotic hexokinase I and by the pro-apoptotic creatine kinase are mutually exclusive, indicating that the absence of hexokinase I allows creatine kinase to bind and open VDAC. [7] Furthermore, hexokinase I has demonstrated anti-apoptotic activity by antagonizing Bcl-2 proteins located at the OMM, which then inhibits TNF-induced apoptosis. [6] [13]

In the prefrontal cortex, hexokinase I putatively forms a protein complex with EAAT2, Na+/K+ ATPase, and aconitase, which functions to remove glutamate from the perisynaptic space and maintain low basal levels in the synaptic cleft. [15]

In particular, hexokinase I is the most ubiquitously expressed isoform out of the four hexokinases, and constitutively expressed in most tissues, though it is majorly found in brain, kidney, and red blood cells (RBCs). [6] [8] [13] [7] [15] [10] [16] Its high abundance in the retina, specifically the photoreceptor inner segment, outer plexiform layer, inner nuclear layer, inner plexiform layer, and ganglion cell layer, attests to its crucial metabolic purpose. [17] It is also expressed in cells derived from hematopoietic stem cells, such as RBCs, leukocytes, and platelets, as well as from erythroid-progenitor cells. [6] Of note, hexokinase I is the sole hexokinase isoform found in the cells and tissues which rely most heavily on glucose metabolism for their function, including brain, erythrocytes, platelets, leukocytes, and fibroblasts. [18] In rats, it is also the predominant hexokinase in fetal tissues, likely due to their constitutive glucose utilization. [12] [16]

Clinical significance

Mutations in this gene are associated with type 4H of Charcot–Marie–Tooth disease, also known as Russe-type hereditary motor and sensory neuropathy (HMSNR). [19] Changes in hexokinase I have also been identified to cause both mild and severe forms of congenital hyperinsulinism. [20] [21] [22] Due to the crucial role of hexokinase I in glycolysis, hexokinase deficiency has been identified as a cause of erythroenzymopathies associated with hereditary non-spherocytic hemolytic anemia (HNSHA). Likewise, hexokinase I deficiency has resulted in cerebral white matter injury, malformations, and psychomotor retardation, as well as latent diabetes mellitus and panmyelopathy. [6] Meanwhile, hexokinase I is highly expressed in cancers, and its anti-apoptotic effects have been observed in highly glycolytic hepatoma cells. [13] [6]

Neurodegenerative disorders

Hexokinase I may be causally linked to mood and psychotic disorders, including unipolar depression (UPD), bipolar disorder (BPD), and schizophrenia via both its roles in energy metabolism and cell survival. For instance, the accumulation of lactate in the brains of BPD and SCHZ patients potentially results from the decoupling of hexokinase I from the OMM, and by extension, glycolysis from mitochondrial oxidative, phosphorylation. In the case of SCHZ, decreasing hexokinase I attachment to the OMM in the parietal cortex resulted in decreased glutamate reuptake capacity and, thus, glutamate spillover from the synapses. The released glutamate activates extrasynaptic glutamate receptors, leading to altered structure and function of glutamate circuits, synaptic plasticity, frontal cortical dysfunction, and ultimately, the cognitive deficits characteristic of SCHZ. [15] Similarly, hexokinase I mitochondrial detachment has been associated with hypothyroidism, which involves abnormal brain development and increased risk for depression, while its attachment leads to neural growth. [14] In Parkinson's disease, hexokinase I detachment from VDAC via Parkin-mediated ubiquitylation and degradation disrupts the MPTP on depolarized mitochondria, consequently blocking mitochondrial localization of Parkin and halting glycolysis. [7] Further research is required to determine the relative hexokinase I detachment needed in various cell types for different psychiatric disorders. This research can also contribute to developing therapies to target causes of the detachment, from gene mutations to interference by factors such as beta-amyloid peptide and insulin. [14]

Retinitis pigmentosa

A heterozygous missense mutation in the HK1 gene (a change at position 847 from glutamate to lysine) has been linked to retinitis pigmentosa. [23] [17] Since this substitution mutation is located far from known functional sites and does not impair the enzyme's glycolytic activity, it is likely that the mutation acts through another biological mechanism unique to the retina. [23] Notably, studies in mouse retina reveal interactions between hexokinase I, the mitochondrial metallochaperone Cox11, and the chaperone protein Ranbp2, which serve to maintain normal metabolism and function in the retina. Thus, the mutation may disrupt these interactions and lead to retinal degradation. [17] Alternatively, this mutation may act through the enzyme's anti-apoptotic function, as disrupting the regulation of the hexokinase-mitochondria association by insulin receptors could trigger photoreceptor apoptosis and retinal degeneration. [23] [17] In this case, treatments that preserve the hexokinase–mitochondria association may serve as a potential therapeutic approach. [17]

Interactions

Hexokinase I is known to interact with:

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

[[File:
WP534.png go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to Entrezgo to article
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
WP534.png go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to Entrezgo to article
|alt=Glycolysis and Gluconeogenesis edit]]
Glycolysis and Gluconeogenesis edit
  1. The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

See also

Related Research Articles

<span class="mw-page-title-main">Glycolysis</span> Series of interconnected biochemical reactions

Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Phosphorylation</span> Chemical process of introducing a phosphate

In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Hexokinase</span> Class of enzymes

A hexokinase is an enzyme that irreversibly phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

<span class="mw-page-title-main">Glucokinase</span> Enzyme participating to the regulation of carbohydrate metabolism

Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.

In oncology, the Warburg effect is the observation that most cancer use aerobic glycolysis for energy generation rather than the mechanisms used by non-cancerous cells. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The existence of the Warburg effect has fuelled popular misconceptions that cancer can be treated by dietary reductions in sugar and carbohydrate.

<span class="mw-page-title-main">Glucose-6-phosphate isomerase</span> Mammalian protein found in Homo sapiens

Glucose-6-phosphate isomerase (GPI), alternatively known as phosphoglucose isomerase/phosphoglucoisomerase (PGI) or phosphohexose isomerase (PHI), is an enzyme that in humans is encoded by the GPI gene on chromosome 19. This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme that interconverts glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P). Extracellularly, the encoded protein functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor (AMF) based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia, and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

<span class="mw-page-title-main">Glucose-6-phosphate dehydrogenase</span> Enzyme involved in the production of energy by cells

Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) (EC 1.1.1.49) is a cytosolic enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Tumor metabolome</span>

The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.

Enzyme activators are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate affinity as well as catalytic activity in the enzyme's other subunits, and thus the substrate acts as an activator.

<span class="mw-page-title-main">Dynamin-like 120 kDa protein</span> Protein-coding gene in the species Homo sapiens

Dynamin-like 120 kDa protein, mitochondrial is a protein that in humans is encoded by the OPA1 gene. This protein regulates mitochondrial fusion and cristae structure in the inner mitochondrial membrane (IMM) and contributes to ATP synthesis and apoptosis, and small, round mitochondria. Mutations in this gene have been implicated in dominant optic atrophy (DOA), leading to loss in vision, hearing, muscle contraction, and related dysfunctions.

<span class="mw-page-title-main">GOT2</span> Mitochondrial enzyme involved in amino acid metabolism

Aspartate aminotransferase, mitochondrial is an enzyme that in humans is encoded by the GOT2 gene. Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and Kreb's cycle. Also, GOT2 is a major participant in the malate-aspartate shuttle, which is a passage from the cytosol to the mitochondria. The two enzymes are homodimeric and show close homology. GOT2 has been seen to have a role in cell proliferation, especially in terms of tumor growth.

<span class="mw-page-title-main">MTCH1</span> Protein-coding gene in the species Homo sapiens

Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a protein that in humans is encoded by the MTCH1 gene on chromosome 6. MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer's disease (AD).

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

<span class="mw-page-title-main">ALAS2</span> Protein-coding gene in humans

Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene. ALAS2 is an aminolevulinic acid synthase.

<span class="mw-page-title-main">Hexokinase II</span> Mammalian protein found in humans

Hexokinase II, also known as Hexokinase B and HK2, is an enzyme which in humans is encoded by the HK2 gene on chromosome 2. Hexokinases phosphorylate glucose to produce glucose 6-phosphate, the first step in most glucose metabolism pathways. Hexokinase II is the predominant hexokinase form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of the HK2 gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]

<span class="mw-page-title-main">Hexokinase III</span> Mammalian protein found in Homo sapiens

Hexokinase III, also known as hexokinase C, is an enzyme which in humans is encoded by the Hk3 gene on chromosome 5. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Similar to hexokinases I and II, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

<span class="mw-page-title-main">TP53-inducible glycolysis and apoptosis regulator</span> Protein-coding gene in the species Homo sapiens

The TP53-inducible glycolysis and apoptosis regulator (TIGAR) also known as fructose-2,6-bisphosphatase TIGAR is an enzyme that in humans is encoded by the C12orf5 gene.

<span class="mw-page-title-main">HKDC1</span> Protein-coding gene in the species Homo sapiens

Hexokinase domain containing 1 (HKDC1) is an enzyme which in humans is encoded by the HKDC1 gene on chromosome 10. It is a recently discovered hexokinase isoform that likely phosphorylates glucose in maternal metabolism during pregnancy.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000156515 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037012 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: HK1 hexokinase 1".
  6. 1 2 3 4 5 6 7 8 9 10 Murakami K, Kanno H, Tancabelic J, Fujii H (2002). "Gene expression and biological significance of hexokinase in erythroid cells". Acta Haematologica. 108 (4): 204–209. doi:10.1159/000065656. PMID   12432216. S2CID   23521290.
  7. 1 2 3 4 5 6 7 8 9 10 11 Okatsu K, Iemura S, Koyano F, Go E, Kimura M, Natsume T, et al. (November 2012). "Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase". Biochemical and Biophysical Research Communications. 428 (1): 197–202. doi:10.1016/j.bbrc.2012.10.041. PMID   23068103.
  8. 1 2 3 4 5 6 7 Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB (January 1998). "The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate". Structure. 6 (1): 39–50. doi: 10.1016/s0969-2126(98)00006-9 . PMID   9493266.
  9. 1 2 Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB (March 2000). "Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation". Journal of Molecular Biology. 296 (4): 1001–1015. doi:10.1006/jmbi.1999.3494. PMID   10686099.
  10. 1 2 3 4 5 6 7 8 9 Robey RB, Hay N (August 2006). "Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt". Oncogene. 25 (34): 4683–4696. doi: 10.1038/sj.onc.1209595 . PMID   16892082.
  11. Cárdenas ML, Cornish-Bowden A, Ureta T (March 1998). "Evolution and regulatory role of the hexokinases". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1401 (3): 242–264. doi: 10.1016/s0167-4889(97)00150-x . PMID   9540816.
  12. 1 2 3 4 Printz RL, Osawa H, Ardehali H, Koch S, Granner DK (February 1997). "Hexokinase II gene: structure, regulation and promoter organization". Biochemical Society Transactions. 25 (1): 107–112. doi:10.1042/bst0250107. PMID   9056853.
  13. 1 2 3 4 5 Schindler A, Foley E (December 2013). "Hexokinase 1 blocks apoptotic signals at the mitochondria". Cellular Signalling. 25 (12): 2685–2692. doi:10.1016/j.cellsig.2013.08.035. PMID   24018046.
  14. 1 2 3 4 5 6 Regenold WT, Pratt M, Nekkalapu S, Shapiro PS, Kristian T, Fiskum G (January 2012). "Mitochondrial detachment of hexokinase 1 in mood and psychotic disorders: implications for brain energy metabolism and neurotrophic signaling". Journal of Psychiatric Research. 46 (1): 95–104. doi:10.1016/j.jpsychires.2011.09.018. PMID   22018957.
  15. 1 2 3 4 5 6 7 Shan D, Mount D, Moore S, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE (April 2014). "Abnormal partitioning of hexokinase 1 suggests disruption of a glutamate transport protein complex in schizophrenia". Schizophrenia Research. 154 (1–3): 1–13. doi:10.1016/j.schres.2014.01.028. PMC   4151500 . PMID   24560881.
  16. 1 2 Reid S, Masters C (1985). "On the developmental properties and tissue interactions of hexokinase". Mechanisms of Ageing and Development. 31 (2): 197–212. doi:10.1016/s0047-6374(85)80030-0. PMID   4058069. S2CID   40877603.
  17. 1 2 3 4 5 Wang F, Wang Y, Zhang B, Zhao L, Lyubasyuk V, Wang K, et al. (October 2014). "A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa". Investigative Ophthalmology & Visual Science. 55 (11): 7159–7164. doi:10.1167/iovs.14-15520. PMC   4224578 . PMID   25316723.
  18. Gjesing AP, Nielsen AA, Brandslund I, Christensen C, Sandbæk A, Jørgensen T, et al. (July 2011). "Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes". BMC Medical Genetics. 12: 99. doi: 10.1186/1471-2350-12-99 . PMC   3161933 . PMID   21781351.
  19. Online Mendelian Inheritance in Man (OMIM): 605285
  20. Hewat TI, Johnson MB, Flanagan SE (7 July 2022). "Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease". Frontiers in Endocrinology. 13: 873254. doi: 10.3389/fendo.2022.873254 . PMC   9302115 . PMID   35872984.
  21. Rosenfeld E, Ganguly A, De Leon DD (December 2019). "Congenital hyperinsulinism disorders: Genetic and clinical characteristics". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 181 (4): 682–692. doi:10.1002/ajmg.c.31737. PMC   7229866 . PMID   31414570.
  22. Maiorana A, Lepri FR, Novelli A, Dionisi-Vici C (2022-03-29). "Hypoglycaemia Metabolic Gene Panel Testing". Frontiers in Endocrinology. 13: 826167. doi: 10.3389/fendo.2022.826167 . PMC   9001947 . PMID   35422763.
  23. 1 2 3 Sullivan LS, Koboldt DC, Bowne SJ, Lang S, Blanton SH, Cadena E, et al. (September 2014). "A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa". Investigative Ophthalmology & Visual Science. 55 (11): 7147–7158. doi:10.1167/iovs.14-15419. PMC   4224580 . PMID   25190649.

Further reading