Hexokinase: 1st glycolysis enzyme. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 10 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome A protein isoform is a version of a Protein with only small differences to another isoform of the same protein A taxon (plural taxa) or taxonomic unit, is a name designating an organism or a group of Organisms In Biological nomenclature according to Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus In Chemistry, a homologous series is a series of Organic compounds with a similar General formula, possessing similar chemical properties due to the presence The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy In Organic chemistry, a hexose is a Monosaccharide with six Carbon atoms having the Chemical formula C6H12O6 Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine In Organic chemistry, a hexose is a Monosaccharide with six Carbon atoms having the Chemical formula C6H12O6 A phosphate, an Inorganic chemical, is a salt of Phosphoric acid. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Glucose 6-phosphate (also known as Robison ester) is Glucose sugar Phosphorylated on carbon 6 A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Variation across species Hexokinases have been found in every organism checked ranging from bacteria, Yeast, and Plants to humans and other Vertebrates The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them This article is about the Enzyme Commission codes For the European Commission system for coding chemicals see EC-No. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 2 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome This article is about the Enzyme Commission codes For the European Commission system for coding chemicals see EC-No. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 5 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome This article is about the Enzyme Commission codes For the European Commission system for coding chemicals see EC-No. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences Left: without glucose (shown the Glc binding pocket) (PDB code=1hkg). Right: with glucose (PDB code=2yhx)

A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule Sugar is a class of edible Crystalline substances mainly Sucrose, Lactose, and Fructose. In Organic chemistry, a hexose is a Monosaccharide with six Carbon atoms having the Chemical formula C6H12O6 In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Glucose 6-phosphate (also known as Robison ester) is Glucose sugar Phosphorylated on carbon 6

Variation across species

Hexokinases have been found in every organism checked, ranging from bacteria, yeast, and plants to humans and other vertebrates. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described Plants are living Organisms belonging to the kingdom Plantae. Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes They are categorized as actin fold proteins, sharing a common ATP binding site core surrounded by more variable sequences that determine substrate affinities and other properties. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Several hexokinase isoforms or isozymes providing different functions can occur in a single species. Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction In Biology, a species is one of the basic units of Biological classification and a Taxonomic rank.

Reaction

The intracellular reactions mediated by hexokinases can be typified as:

Hexose-CH₂OH + MgATP⁼ → Hexose-CH₂O-PO₃⁼ + MgADP^- + H⁺

where Hexose-CH₂OH represents any of several hexoses (like glucose) that contain an accessible -CH₂OH moiety.

Consequences of hexose phosphorylation

Phosphorylation of a hexose (such as glucose) often commits it to a limited number of intracellular metabolic processes (such as glycolysis or glycogen synthesis). See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells This is aided by the fact that phosphorylation also makes it unable to move or be transported out of the cell.

Size of different isoforms

Most bacterial hexokinases are approximately 50kD in size. Multicellular organisms such as plants and animals often have more than one hexokinase isoform. Most are about 100kD in size, and consist of two halves (N and C terminal), which share much sequence homology. This suggests an evolutionary origin by duplication and fusion of a 50kD ancestral hexokinase similar to those of bacteria.

Types of mammalian hexokinase

There are four important mammalian hexokinase isozymes (EC 2.7.1.1) that vary somewhat in their subcellular locations, kinetic characteristics with respect to different substrates and operating conditions, and physiological function. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands This article is about the Enzyme Commission codes For the European Commission system for coding chemicals see EC-No. They are designated hexokinases I, II, III, and IV or hexokinases A, B, C, and D.

Hexokinases I, II, and III

Hexokinases I, II, and III are referred to as "low-K_m" isozymes because of a high affinity for glucose even at low concentrations (below 1 mM). Hexokinases I and II follow Michaelis-Menten kinetics at physiologic concentrations of substrates. All three are strongly inhibited by their product, glucose-6-phosphate. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. Glucose 6-phosphate (also known as Robison ester) is Glucose sugar Phosphorylated on carbon 6 Molecular weights are around 100 kD. The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one Each consists of two similar 50kD halves, but only in hexokinase II do both halves have functional active sites.

• Hexokinase I (hexokinase A) is found in all mammalian tissues, and is considered a "housekeeping enzyme," unaffected by most physiological, hormonal, and metabolic changes.

• Hexokinase III (or C) is inhibited by excessive glucose (substrate inhibition).

Hexokinase IV ("glucokinase")

Mammalian hexokinase IV, also referred to as glucokinase, has unique characteristics and functions compared to other hexokinases. Glucokinase ( is an Enzyme that facilitates Phosphorylation of Glucose to Glucose-6-phosphate.

• The location of the phosphorylation on a subcellular level occurs when glucokinase translocates between the cytoplasm and nucleus of liver cells. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule Glucokinase ( is an Enzyme that facilitates Phosphorylation of Glucose to Glucose-6-phosphate. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed The liver is a vital organ in the human body and is present in Vertebrates and some other animals Glucokinase can only phosphorylate glucose if the concentration of this substrate is high enough; its Km for glucose is 100 times higher than that of hexokinases I, II, and III.

• It is monomeric, about 50kD, displays positive cooperativity with glucose, and is not allosterically inhibited by its product, glucose-6-phosphate. In Biochemistry, allosteric regulation is the regulation of an Enzyme or other Protein by binding an effector molecule at the protein's allosteric

It is present in the liver, pancreas, hypothalamus, small intestine, and perhaps certain other neuroendocrine cells, and plays an important regulatory role in carbohydrate metabolism. The liver is a vital organ in the human body and is present in Vertebrates and some other animals The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises Neuroendocrine nʊəroʊˈɛndəkrɪn cells are cells that release a hormone into the circulating blood in response to a neural stimulus Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of Carbohydrates

• In the beta cells of the pancreatic islets, it serves as a glucose sensor to control insulin release, and similarly controls glucagon release in the alpha cells. Beta cells ( beta-cells, β-cells) are a type of cell in the Pancreas in areas called the Islets of Langerhans. Islets of Langerhans is the area in which the Endocrine (ie hormone-producing cells of the Pancreas are grouped Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Glucagon is an important Hormone involved in Carbohydrate metabolism. Alpha cells are endocrine cells in the Islets of Langerhans of the Pancreas.

• In hepatocytes of the liver, glucokinase responds to changes of ambient glucose levels by increasing or reducing glycogen synthesis. Hepatocytes make up 70-80% of the Cytoplasmic mass of the Liver.

Hexokinase in glycolysis

The use of glucose as an energy source in cells is via the metabolic pathway known as glycolysis. In Biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized The first step of this sequence of reactions is the phosphorylation of glucose by hexokinase to prepare it for later breakdown in order to provide energy. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule

D-Glucose	Hexokinase		α-D-Glucose-6-phosphate
	ATP	ADP

Compound C00031 at KEGG Pathway Database. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Glucose 6-phosphate (also known as Robison ester) is Glucose sugar Phosphorylated on carbon 6 Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine KEGG ( Kyoto Encyclopedia of Genes and Genomes) is a collection of Online databases dealing with Genomes Enzymatic pathways and biological chemicals Enzyme 2.7.1.1 at KEGG Pathway Database. KEGG ( Kyoto Encyclopedia of Genes and Genomes) is a collection of Online databases dealing with Genomes Enzymatic pathways and biological chemicals Compound C00668 at KEGG Pathway Database. KEGG ( Kyoto Encyclopedia of Genes and Genomes) is a collection of Online databases dealing with Genomes Enzymatic pathways and biological chemicals Reaction R01786 at KEGG Pathway Database. KEGG ( Kyoto Encyclopedia of Genes and Genomes) is a collection of Online databases dealing with Genomes Enzymatic pathways and biological chemicals

The major reason for the immediate phosphorylation of glucose by a hexokinase is to prevent diffusion out of the cell. The phosphorylation adds a charged phosphate group so the glucose 6-phosphate cannot easily cross the cell membrane. A phosphate, an Inorganic chemical, is a salt of Phosphoric acid. Glucose 6-phosphate (also known as Robison ester) is Glucose sugar Phosphorylated on carbon 6

Association to mitochondria

Hexokinases I, II, and III can associate physically to the outer surface of the external membrane of mitochondria through specific binding to a porin (or Voltage Dependent Anion Channel). In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. This association confers hexokinase direct access to mitochondrially-generated ATP, which is one of the two substrates of hexokinase. Mitochondrial hexokinase is highly elevated in rapidly-growing malignant tumor cells, with levels up to 200 times higher than normal tissues. Mitochondrially-bound hexokinase has been demonstrated to be the driving force^[1] for the extremely high glycolytic rates that take place aerobically in tumor cells (the so-called Warburg effect described by Otto Warburg in 1930). Otto Warburg (1859-1938 was a botanist and industrial agriculture expert and an active member of the World Zionist Organization, which worked toward the re-establishment of

See also

• glucokinase
• glycolysis
• glycogen
• insulin
• Glucose 6-phosphatase

References

1. ^ Bustamante E, Pedersen P (1977). Glucokinase ( is an Enzyme that facilitates Phosphorylation of Glucose to Glucose-6-phosphate. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Glucose 6-phosphatase (Glc-6-Pase is an Enzyme that hydrolyzes Glucose-6-phosphate resulting in the creation of a phosphate group and free glucose "High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase". Proc Natl Acad Sci U S A 74 (9): 3735-9. doi:10.1073/pnas.74.9.3735. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 198801.  

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Glucose Hexokinase Glucose-6-phosphate Glucose-6-phosphate isomerase Fructose 6-phosphate 6-phosphofructokinase Fructose 1,6-bisphosphate Fructose bisphosphate aldolase Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Triosephosphate isomerase Glyceraldehyde 3-phosphate Glyceraldehyde-3-phosphate dehydrogenase ATP ADP ATP ADP NAD+ + Pi NADH + H+ + 2 NAD+ + Pi NADH + H+ 1,3-Bisphosphoglycerate Phosphoglycerate kinase 3-Phosphoglycerate Phosphoglycerate mutase 2-Phosphoglycerate Phosphopyruvate hydratase(Enolase) Phosphoenolpyruvate Pyruvate kinase Pyruvate Pyruvate dehydrogenase Acetyl-CoA ADP ATP H2O ADP ATP CoA + NAD+ NADH + H+ + CO2 2 2 2 2 2 2 ADP ATP H2O