Hexokinase domain-containing protein-1 in metabolic diseases and beyond

Abstract

Hexokinase (HK) domain-containing protein-1 (HKDC1) is a widely expressed novel HK.Recent studies aimed at understanding the functionality of HKDC1 have identified roles for HKDC1 that extend beyond glucose sensing and phosphorylation.Genome-wide association studies have identified genetic variants of HKDC1 that are associated with 2-h blood glucose levels during an oral glucose tolerance test performed in pregnancy, as well as with hemoglobin A1c, suggesting a link between HKDC1 and diabetes.Mouse models indicate that HKDC1 is important for glucose utilization and homeostasis during times of metabolic stress.Beyond glucose metabolism, recent studies suggest roles for HKDC1 in the survival, progression, and metastases of several human cancers, conferring a poorer prognosis. Glucose phosphorylation by hexokinases (HKs) traps glucose in cells and facilitates its usage in metabolic processes dependent on cellular needs. HK domain-containing protein-1 (HKDC1) is a recently discovered protein with wide expression containing HK activity, first noted through a genome-wide association study (GWAS) to be linked with gestational glucose homeostasis during pregnancy. Since then, HKDC1 has been observed to be expressed in many human tissues. Moreover, studies have shown that HKDC1 plays a role in glucose homeostasis by which it may affect the progression of many pathophysiological conditions such as gestational diabetes mellitus (GDM), nonalcoholic steatohepatitis (NASH), and cancer. Here, we review the key studies contributing to our current understanding of the roles of HKDC1 in human pathophysiological conditions and potential therapeutic interventions. Glucose phosphorylation by hexokinases (HKs) traps glucose in cells and facilitates its usage in metabolic processes dependent on cellular needs. HK domain-containing protein-1 (HKDC1) is a recently discovered protein with wide expression containing HK activity, first noted through a genome-wide association study (GWAS) to be linked with gestational glucose homeostasis during pregnancy. Since then, HKDC1 has been observed to be expressed in many human tissues. Moreover, studies have shown that HKDC1 plays a role in glucose homeostasis by which it may affect the progression of many pathophysiological conditions such as gestational diabetes mellitus (GDM), nonalcoholic steatohepatitis (NASH), and cancer. Here, we review the key studies contributing to our current understanding of the roles of HKDC1 in human pathophysiological conditions and potential therapeutic interventions. On cell entry, HKs (see Glossary) phosphorylate hexose sugars, primarily glucose, trapping these sugars in the cell and facilitating their usage in metabolic processes dependent on cellular needs [1.Wilson J.E. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function.J. Exp. Biol. 2003; 206: 2049-2057Crossref PubMed Scopus (700) Google Scholar, 2.Kanno H. Hexokinase: gene structure and mutations.Baillieres Best Pract. Res. Clin. Haematol. 2000; 13: 83-88Crossref PubMed Scopus (20) Google Scholar, 3.Bowden-Cornish A. et al.Hexokinase and ‘glucokinase’ in liver metabolism.Trends Biochem. Sci. 1991; 16: 281-282Abstract Full Text PDF PubMed Scopus (21) Google Scholar]. Four HKs have been characterized and extensively reviewed: HK1–3 have high enzymatic activity and mediate the phosphorylation of glucose for the purpose of cellular utilization, whereas glucokinase (GK) functions as a glucose sensor due to its higher Km that is near physiological blood glucose levels [4.Matschinsky F.M. Glucokinase, glucose homeostasis, and diabetes mellitus.Curr. Diab. Rep. 2005; 5: 171-176Crossref PubMed Scopus (82) Google Scholar, 5.Wilson J.E. Hexokinases.Rev. Physiol. Biochem. Pharmacol. 1995; 126: 65-198Crossref PubMed Google Scholar, 6.Cárdenas M.L. et al.Evolution and regulatory role of the hexokinases.Biochim. Biophys. Acta. 1998; 1401: 242-264Crossref PubMed Scopus (221) Google Scholar, 7.Postic C. et al.Cell-specific roles of glucokinase in glucose metabolism.Recent Prog. Horm. Res. 2001; 56: 195-217Crossref PubMed Scopus (140) Google Scholar]. The HKs are found in a wide range of tissues, but their patterns of expression differ [8.Griffin L.D. et al.Developmental expression of hexokinase 1 in the rat.Biochim. Biophys. Acta. 1992; 1129: 309-317Crossref PubMed Scopus (31) Google Scholar, 9.Postic C. et al.Development and regulation of glucose transporter and hexokinase expression in rat.Am. J. Phys. 1994; 266: E548-E559PubMed Google Scholar, 10.Coerver K.A. et al.Developmental expression of hexokinase 1 and 3 in rats.Histochem. Cell Biol. 1998; 109: 75-86Crossref PubMed Scopus (20) Google Scholar, 11.Printz R.L. et al.Mammalian glucokinase.Annu. Rev. Nutr. 1993; 13: 463-496Crossref PubMed Scopus (168) Google Scholar]. In the mid-2000s, in an effort to better understand the evolutionary relationships of the HKs and to explain the evolution of GK and the diversification of the HKs, phylogenetic analyses were performed, which uncovered a novel HK-like gene called HKDC1 [12.Irwin D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Scholar]. HKDC1 lies on chromosome 10 adjacent to HK1 and encodes a 100-kDa protein product sharing approximately 70% sequence homology with HK1 [12.Irwin D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Scholar,13.Ludvik A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google Scholar]. Review of the human Expressed Sequence Tags (EST) database suggested that HKDC1 was widely expressed, and given its homology to HK1, along with the significance of the HKs for glucose metabolism, this preliminary study proposed that HKDC1 is, in fact, another HK. Studies utilizing a human EST database [12.Irwin D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Scholar] and tissue samples from the Genotype-Tissue Expression Consortium [13.Ludvik A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google Scholar] have found HKDC1 in a wide range of human and mouse tissues. Confirming this mRNA data, Khan et al. [14.Khan M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google Scholar] performed analyses on human and that HKDC1 protein expression is widely review of the key from HKDC1 mRNA and protein expression is in 1 and and with high levels of HKDC1 gene EST was in The in the of et al. be found at D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Expression A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google was in The in the of et al. be found at in a analyses of HKDC1 protein HKDC1 expression to the cells of the A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google expression in expression in the A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google by the of and it to of in M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google to in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in in and M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google the the HKDC1 was in cells of the in the and M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the and M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google to in in the in M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the and to in M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in in M.W. et al.Studies on the tissue localization of a novel fifth in PubMed Scopus Google in the in HKDC1 by the of and it to of In the the HKDC1 was in cells of the in a the sequence homology with HK1, it was that HKDC1 functions to the of the sequence of HKDC1 in with HKs the of conserved in the and that are to be for glucose and [12.Irwin D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Scholar]. The of these that HKDC1 may as a HK. test this et al. C. et regulatory associated with gestational expression of the novel hexokinase PubMed Scopus Google Scholar] with containing HKDC1 from a human HK activity from cell utilizing of cells HK the expression of the HKs was by the expression of the found that cells in HKDC1 protein and HK activity the range of glucose the in the suggested that HKDC1 has a Km these suggested that HKDC1 to cellular HK activity through HK activity of the activity of the HKDC1 has HK activity, the and utilizing a HK in found that HKDC1 of the activity of HK1 the these studies that HKDC1 is a widely expressed fifth in understanding the of HKDC1 in the role of HKDC1 as a HK was it was that its potential for physiological was HKDC1 is conserved between vertebrate and is expressed in a of human [12.Irwin D.M. Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene.Comp. Biochem. Physiol. D Genomics Proteomics. 2007; 3: 96-107Crossref PubMed Scopus (43) Google Scholar]. Since then, genetic studies have uncovered between genetic in HKDC1 and The first in the of HKDC1 functionality several gene variants in HKDC1 were identified to be in association with glucose during a the genetic during et of HKDC1 and as during through genome-wide association PubMed Scopus Google Scholar]. the and to the genetic associated with during in of et and J. PubMed Scopus Google The and J. PubMed Scopus Google Scholar]. a of in the et al. et of HKDC1 and as during through genome-wide association PubMed Scopus Google Scholar] samples and from of and and of genome-wide were to genetic variants associated with glucose and levels and and 2-h glucose levels during an oral glucose tolerance test The with the association in the was with of the first of The genetic of HKDC1 a of HK1 The from the a association with several The with the association was which genome-wide significance in a the variants near HKDC1 were identified in of and and the of regulatory et of the human regulatory from PubMed Scopus Google Scholar]. linked for the first to a potential physiological during et association analyses and the PubMed Scopus Google variants of HKDC1 and their et at et of HKDC1 and as during through genome-wide association PubMed Scopus Google et from et al. at C. et regulatory associated with gestational expression of the novel hexokinase PubMed Scopus Google et with glucose 1 and during et al.Hexokinase containing 1 gene variants and their association with gestational diabetes mellitus in a 2016; PubMed Scopus Google et glucose 1 and during et of genome-wide association studies of and in a gestational diabetes mellitus from PubMed Scopus Google et on and with et in and at identified by J. 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PubMed Scopus Google Scholar]. in have been in to in this study HKDC1 to a role et diabetes mellitus and at a review and of therapeutic Clin. PubMed Scopus Google et a of in J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar]. genetic studies have to the role of HKDC1 in and human of the a human genetic database from a utilizing a of a genetic link between at HKDC1 variants and hemoglobin variants differ from 2-h glucose levels during pregnancy, with to affect In with HKDC1 with levels an during pregnancy, as well as with these studies for roles of HKDC1 variants in glucose and studies have mouse models to the expression of HKDC1 and in an et al. [13.Ludvik A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google Scholar] and a mouse in which HKDC1 was in In to an at of glucose with was to glucose the as glucose was during an glucose tolerance were due to in an such as a in blood glucose, glucose The of HKDC1 was in to at of which is the of during mouse et to gestational glucose J. Physiol. PubMed Scopus Google Scholar]. to glucose with during an and at of a in glucose tolerance with suggested an of HKDC1 on glucose during times of metabolic such as in of HKDC1 the first study to the role of HKDC1 in glucose by genetic mouse et al. [13.Ludvik A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google Scholar] a gene to HKDC1 expression through cells from the and by the In these a was the HKDC1 gene a gene utilizing an were whereas the of the at the of to this an approximately in HKDC1 expression and were for this that HKDC1 may have a role in et al. et HKDC1 as a gene associated with Google Scholar] HKDC1 the significance of the in and another is have in and GK et al.Hexokinase of in glucose tolerance in Biol. Full Text Full Text PDF PubMed Scopus Google C. et roles for glucokinase in glucose homeostasis as by liver and gene Biol. Full Text Full Text PDF PubMed Scopus Google Scholar]. the first study to the role of HKDC1 in glucose by genetic mouse et al. 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Full Text Full Text PDF PubMed Scopus Google Scholar]. glucose tolerance in the of in studies were performed [13.Ludvik A.E. et al.HKDC1 is a novel hexokinase involved in whole-body glucose use.Endocrinology. 2016; 157: 3452-3461Crossref PubMed Scopus (36) Google Scholar]. of the of that these levels of and levels in utilizing an oral of to whole-body glucose utilization during an the of glucose found in with high HKDC1 such as the and was in in and to levels in tissues. suggest that HKDC1 has roles in and the glucose by with the glucose tolerance in and studies with HKDC1 suggest that HKDC1 is important for whole-body glucose utilization and conditions of metabolic and with the that HKDC1 is associated with 2-h glucose levels an at gestational in Khan et al. M.W. et hexokinase containing 1 (HKDC1) glucose tolerance and in Biophys. PubMed Scopus Google Scholar] recently in an HKDC1 mouse that during the of in of HKDC1 expression the was in these HKDC1 this with HKDC1 tolerance with of the of with HKDC1 it was shown that was phosphorylation of protein with Moreover, with in was glucose during a with HKDC1 this involved in a with HKDC1 this study in the HKDC1 higher and the suggesting study that HKDC1 the whole-body by glucose and of et al. M.W. et hexokinase containing 1 (HKDC1) glucose tolerance and in Biophys. PubMed Scopus Google Scholar] containing human HKDC1 in for the of of HKDC1 on glucose in were in the with containing HKDC1 human HKDC1 with containing as were at of were in the with containing a with a as HKDC1 were to pregnancy. and of pregnancy, these HKDC1 were at of pregnancy. Khan et al. M.W. et hexokinase containing 1 (HKDC1) glucose tolerance and in Biophys. 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In a et al. et HKDC1 expression to liver PubMed Scopus Google Scholar] characterized the role of HKDC1 in and a role of HKDC1 in the of nonalcoholic liver In this it was shown that HKDC1 protein has HK activity, to C. et regulatory associated with gestational expression of the novel hexokinase PubMed Scopus Google and that in of human HKDC1 in glucose HKDC1 has HK activity, it that it glucose by its localization to the that HK1 and localization the cellular localization utilizing protein and a the HKDC1 to the whereas the was found in with this of HKDC1 and glucose and suggesting that HKDC1 may in these may to the human liver samples and mouse models to the of HKDC1 mRNA and protein levels in liver et HKDC1 expression to liver PubMed Scopus Google Scholar]. 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Res. 2016; PubMed Scopus Google Scholar] that HKDC1 expression is in human tissue and is with and prognosis. genetic of HKDC1 in and human cell cellular and which was to be due to of and indicate that therapeutic of HKDC1 in may by and et al. et al.HKDC1 the and in Cell PubMed Scopus Google Scholar] found higher levels of HKDC1 mRNA and protein levels in cell in the of HKDC1 protein expression with and with these cells to HKDC1 higher glucose and and and of HKDC1 to phosphorylation of and the phosphorylation of at and that were HKDC1 expression was an role for of and of in cells HKDC1 of and these that HKDC1 the of which is to be through regulation of the that HKDC1 is in cells and tissues, et al. et and by HKDC1 PubMed Scopus Google Scholar] cells and found to et al. et HKDC1 expression to liver PubMed Scopus Google HKDC1 is in the and with 1 to potential and glucose glucose to and the of cell and In with this of HKDC1 activity, and the as a potential therapeutic In a recent et al. et al.HKDC1 by of and PubMed Scopus Google Scholar] of the affect the of cell to HKDC1 expression was in and HKDC1 of the of HKDC1 the sequence in of HKDC1 from and and et al. et HKDC1 expression to liver PubMed Scopus Google Scholar] first that the of HKDC1 was for the potential for the of at along HKDC1 that may the is suggested by these the of study by et al. is the first to that of the in and the first to suggest that this may therapeutic HKDC1 glucose and is widely expressed in tissues, but its role in human to be have that genetic variants of HKDC1 are associated with glucose an during pregnancy. In with this genetic variants of HKDC1 are to suggesting a potential role in HKDC1 expression levels were shown to glucose a glucose during and during suggesting a role for HKDC1 in glucose homeostasis during metabolic studies are to the of HKDC1 in tissue as well as to in HKDC1 expression affect glucose homeostasis conditions (see HKDC1 be a for aimed at in human et al. therapeutic from HKDC1 is a novel potential therapeutic for PubMed Scopus Google Scholar] activity to for a high of for potential the in the for which been was studies suggest roles for HKDC1 in HKDC1 mRNA and protein are expressed in tissue with In the of high HKDC1 cells and survival, whereas of HKDC1 mRNA levels in cells to the of the at the and to cell suggest that HKDC1 therapeutic in cancer. studies are to the of HKDC1 with and to of the between HKDC1 and in understanding the of be in understanding the of HKDC1 in the of and In HKDC1 is a widely expressed protein with HK activity that plays important roles in glucose homeostasis during and and has been linked to progression and poorer in human cancer. HKDC1 has as a of physiological processes and human such as diabetes and cancer. an understanding of the of of HKDC1 are to important for human the of HKDC1 in tissue it is the by which HKDC1 to whole-body glucose utilization and HKDC1 expression levels affect glucose conditions of metabolic genetic variants of HKDC1 to the of are the by which HKDC1 cell survival, and in the the progression of human and are of HKDC1 activity that as for the of potential the of HKDC1 in tissue it is the by which HKDC1 to whole-body glucose utilization and HKDC1 expression levels affect glucose conditions of metabolic genetic variants of HKDC1 to the of are the by which HKDC1 cell survival, and in the the progression of human and are of HKDC1 activity that as for the of potential was by and the and the in the of the the and the the are study that of from with the of genetic associated with a glucose discovered for the first during and to pregnancy. an that an from to sugars In the of glucose, phosphorylation to glucose traps glucose in the it to be to current cellular needs. conserved by cells in to aimed at cellular a that to a sequence in and the expression of a test in which an oral glucose is and blood is at to the to test to the to a in a in the a that may be the of a and of in a be to our to in the that facilitates between the and to the of the of an

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