Pyruvate kinase 508739 198033179 2008-03-13T20:01:25Z Bhorrock 81855 /* See also */ {|align="right" |- |{{Protbox |Name=Pyruvate Kinase 1 |Photo=Pyruvate Kinase 1A3W wpmp.png |Caption={{{!}} align="center" border="0" {{!}} '''Enzyme''' {{!}} Pyruvate Kinase {{!}}- {{!}} '''PDB Code''' {{!}} {{PDB|1A3W}} {{!}}- {{!}} '''Organism''' {{!}} [[Yeast]] {{!}}- {{!}} '''Complexed molecules''' {{!}} FBP, PG, Mn2+ and K+ {{!}}} |HGNCid=9020 |Symbol=PKLR |AltSymbols = |Chromosome = 1 |Arm = q |Band = 21 |LocusSupplementaryData = |Gene= |Gene_type= |Protein_length= |Molecular_weight= |Structure= |Type= |Functions= |Domains= |Motifs= |Alternative_products= |Catalytic_activity= |Cofactors= |Enzyme_regulation= |Km= |Vmax= |Biophysicochemical_properties= |Diseases= |Pharmaceuticals= |Biotechnology= |Taxa= |Cells= |Location= |Mods= |Names= |Pathways= |Interactions= |Actions= |Agonists= |Antagonists= |Accession_numbers= |EntrezGene = |OMIM = |RefSeq = |UniProt = |PDB = |ECnumber = |Codes= {{EntrezGene|5313}}, {{RefSeq|NM_000298}}, {{UniProt|P30613}}, {{OMIM|266200}} {{EC number|2.7.1.40}} |Review= |Pages= }} |- | {{Protbox |Name = Pyruvate kinase 2 |Photo= |Caption= |HGNCid=9021 |Symbol=PKM2 |AltSymbols = |Chromosome=15 |Arm = |Band = |LocusSupplementaryData = |Gene= |Gene_type= |Protein_length= |Molecular_weight= |Structure= |Type= |Functions= |Domains= |Motifs= |Alternative_products= |Catalytic_activity= |Cofactors= |Enzyme_regulation= |Km= |Vmax= |Biophysicochemical_properties= |Diseases= |Pharmaceuticals= |Biotechnology= |Taxa= |Cells= |Location= |Mods= |Names= |Pathways= |Interactions= |Actions= |Agonists= |Antagonists= |Accession_numbers= |EntrezGene = |OMIM = |RefSeq = |UniProt = |PDB = |ECnumber = |Codes={{EntrezGene|5315}}, {{RefSeq|NM_182470}}, {{UniProt|P14618}}, {{OMIM|179050}} {{EC number|2.7.1.40}} |Review= |Pages= }} |} <!-- [[Image:pkb.jpg|thumb|right|250px|''Typical Pyruvate Kinase Structure, <small>X-ray [[Crystallography]] Derived</small>'']] --> '''Pyruvate kinase''' is an [[enzyme]] involved in [[glycolysis]]. It [[catalyst|catalyzes]] the transfer of a [[phosphate group]] from [[phosphoenolpyruvate]] (PEP) to [[adenosine diphosphate|ADP]], yielding one molecule of [[pyruvate]] and one molecule of [[adenosine triphosphate|ATP]]. ==Reaction== The reaction with pyruvate kinase: pyruvate kinase PEP ----------> pyruvate / \ ADP ATP This process also requires a manganese ion. The enzyme is a ''transferase'' under the international classification of enzymes. This step is the final one in the glycolytic pathway, which produces pyruvate molecules. The pyruvate may next be used to regenerate [[NAD+]] via [[fermentation]], or can be converted (as [[acetyl CoA]]) to ATP. ==Regulation== This reaction has a large negative [[free energy]] change, one of three in glycolysis. All three such steps regulate the overall activity of the pathway, and are generally irreversible under [[physiological conditions]]. Pyruvate kinase activity is regulated by: *Its own [[Substrate (biochemistry)|substrate]] PEP and [[fructose 1,6-bisphosphate]], an intermediate in glycolysis; which both enhance enzymatic activity. Thus, glycolysis is driven to operate faster when more substrate is present. *[[Citrate]] and ATP, which allosterically inhibit it. This accounts for parallel regulation with [[PFK 1]]. *[[Alanine]], a negative allosteric modulator Pyruvate kinase is also regulated indirectly by [[insulin]] and [[glucagon]], which control a [[protein kinase]]. This protein kinase phosphorylates pyruvate kinase to inactivate it and dephosphorylates the enzyme to activate it. Glucagon signals fasting (no glucose available), and insulin signals the opposite. These two signaling molecules--in conjunction with the protein kinase--prevent pyruvate kinase from being active at the same time as the enzymes which catalyze the reverse reaction ([[pyruvate carboxylase]] and [[phosphoenolpyruvate carboxykinase]]), preventing a [[futile cycle]]. In fact, to say that the forward reaction and reverse reaction are not both active simultaneously may not be entirely accurate. Futile cycles, also known as substrate cycles, are known to fine-tune flux through metabolic pathways. ==Deficiency== Genetic defects of this enzyme cause the disease known as [[pyruvate kinase deficiency]]. In this condition, a lack of pyruvate kinase slows down the process of glycolysis. This effect is especially devastating in cells that lack [[mitochondria]], because these cells must use [[fermentation (biochemistry)|anaerobic glycolysis]] as their sole source of energy because the [[TCA cycle]] is not available. One example is [[red blood cells]], which in a state of pyruvate kinase deficiency rapidly become deficient in ATP and can undergo [[hemolysis]]. Therefore, pyruvate kinase deficiency can cause [[hemolytic anemia]]. ==Role in gluconeogenesis== Pyruvate kinase also serves as a regulatory enzyme for [[gluconeogenesis]], a biochemical pathway in which the liver generates [[glucose]] from pyruvate and other substrates. When pyruvate kinase is inhibited by [[phosphorylation]] (which occurs in the [[fasting state]], via [[glucagon]]), phosphoenolpyruvate is prevented from conversion to pyruvate. Instead, it is converted to glucose in a series of gluconeogenesis reactions that are mostly (but not exactly) the reverse sequence of glycolysis. The glucose thus produced is expelled from the liver, providing energy for vital tissues in the fasting state. ==See also== * [[PKLR]] * [[Tumor M2-PK]] ==External links== * {{MeshName|Pyruvate+kinase}} {{glycolysis}} {{Kinases}} {{Glycolysis enzymes}} [[Category:Wikipedia articles with ASCII art]] [[de:Pyruvatkinase]] [[fr:Pyruvate kinase]] [[it:Piruvato chinasi]]