3054:
2995:
3161:
674:(ROS) are chemically reactive forms of oxygen. In human lung cells, ROS has been shown to inhibit the M2 isozyme of pyruvate kinase (PKM2). ROS achieves this inhibition by oxidizing Cys358 and inactivating PKM2. As a result of PKM2 inactivation, glucose flux is no longer converted into pyruvate, but is instead utilized in the pentose phosphate pathway, resulting in the reduction and detoxification of ROS. In this manner, the harmful effects of ROS are increased and cause greater oxidative stress on the lung cells, leading to potential tumor formation. This inhibitory mechanism is important because it may suggest that the regulatory mechanisms in PKM2 are responsible for aiding cancer cell resistance to oxidative stress and enhanced tumorigenesis.
549:, glycolysis and gluconeogenesis are heavily regulated in order to ensure that they are never operating in the cell at the same time. As a result, the inhibition of pyruvate kinase by glucagon, cyclic AMP and epinephrine, not only shuts down glycolysis, but also stimulates gluconeogenesis. Alternatively, insulin interferes with the effect of glucagon, cyclic AMP and epinephrine, causing pyruvate kinase to function normally and gluconeogenesis to be shut down. Furthermore, glucose was found to inhibit and disrupt gluconeogenesis, leaving pyruvate kinase activity and glycolysis unaffected. Overall, the interaction between hormones plays a key role in the functioning and regulation of glycolysis and gluconeogenesis in the cell.
561:, is the primary treatment used for type 2 diabetes. Metformin has been shown to indirectly affect pyruvate kinase through the inhibition of gluconeogenesis. Specifically, the addition of metformin is linked to a marked decrease in glucose flux and increase in lactate/pyruvate flux from various metabolic pathways. Although metformin does not directly affect pyruvate kinase activity, it causes a decrease in the concentration of ATP. Due to the allosteric inhibitory effects of ATP on pyruvate kinase, a decrease in ATP results in diminished inhibition and the subsequent stimulation of pyruvate kinase. Consequently, the increase in pyruvate kinase activity directs metabolic flux through glycolysis rather than gluconeogenesis.
3221:
2844:
2766:
3102:
2942:
2880:
2802:
537:, which serves as a covalent modifier by phosphorylating and deactivating pyruvate kinase. In contrast, the secretion of insulin in response to blood sugar elevation activates phosphoprotein phosphatase I, causing the dephosphorylation and activation of pyruvate kinase to increase glycolysis. The same covalent modification has the opposite effect on gluconeogenesis enzymes. This regulation system is responsible for the avoidance of a futile cycle through the prevention of simultaneous activation of pyruvate kinase and enzymes that catalyze gluconeogenesis.
2861:
2783:
29:
3029:
2965:
2923:
2819:
704:
3125:
2897:
3196:
3085:
700:(ERK2) causes conformational changes that allow PKM2 to enter the nucleus and regulate glycolytic gene expression required for tumor development. Some studies state that there is a shift in expression from PKM1 to PKM2 during carcinogenesis. Tumor microenvironments like hypoxia activate transcription factors like the hypoxia-inducible factor to promote the transcription of PKM2, which forms a positive feedback loop to enhance its own transcription.
4870:
2741:
483:, and the transfer of phosphate from PEP to ADP by pyruvate kinase. Under wild-type conditions, all three of these reactions are irreversible, have a large negative free energy and are responsible for the regulation of this pathway. Pyruvate kinase activity is most broadly regulated by allosteric effectors, covalent modifiers and hormonal control. However, the most significant pyruvate kinase regulator is
386:
3244:
299:. The R and L isozymes differ from M1 and M2 in that they are allosterically regulated. Kinetically, the R and L isozymes of pyruvate kinase have two distinct conformation states; one with a high substrate affinity and one with a low substrate affinity. The R-state, characterized by high substrate affinity, serves as the activated form of pyruvate kinase and is stabilized by PEP and
326:. The PKM gene is regulated through heterogenous ribonucleotide proteins like hnRNPA1 and hnRNPA2. Human PKM2 monomer has 531 amino acids and is a single chain divided into A, B and C domains. The difference in amino acid sequence between PKM1 and PKM2 allows PKM2 to be allosterically regulated by FBP and for it to form dimers and tetramers while PKM1 can only form tetramers.
413:(FBP,) was found to be enhanced by the presence of Mg. Therefore, Mg was concluded to be an important cofactor in the catalysis of PEP into pyruvate by pyruvate kinase. Furthermore, the metal ion Mn was shown to have a similar, but stronger effect on YPK than Mg. The binding of metal ions to the metal binding sites on pyruvate kinase enhances the rate of this reaction.
307:, causing phosphorylation of pyruvate kinase and the inhibition of glycolysis. The M2 isozyme of pyruvate kinase can form tetramers or dimers. Tetramers have a high affinity for PEP, whereas, dimers have a low affinity for PEP. Enzymatic activity can be regulated by phosphorylating highly active tetramers of PKM2 into an inactive dimers.
572:(hnRNPs) can act on the PKM gene to regulate expression of M1 and M2 isoforms. PKM1 and PKM2 isoforms are splice variants of the PKM gene that differ by a single exon. Various types of hnRNPs such as hnRNPA1 and hnRNPA2 enter the nucleus during hypoxia conditions and modulate expression such that PKM2 is up-regulated. Hormones such as
3053:
2994:
381:
of pyruvate. Secondly, a proton must be added to the enolate of pyruvate to produce the functional form of pyruvate that the cell requires. Because the substrate for pyruvate kinase is a simple phospho-sugar, and the product is an ATP, pyruvate kinase is a possible foundation enzyme for the evolution
695:
Cancer cells have characteristically accelerated metabolic machinery and
Pyruvate Kinase is believed to have a role in cancer. When compared to healthy cells, cancer cells have elevated levels of the PKM2 isoform, specifically the low activity dimer. Therefore, PKM2 serum levels are used as markers
420:
are the slower, regulated steps of a pathway and thus determine the overall rate of the pathway. In glycolysis, the rate-limiting steps are coupled to either the hydrolysis of ATP or the phosphorylation of ADP, causing the pathway to be energetically favorable and essentially irreversible in cells.
682:
Phenylalanine is found to function as a competitive inhibitor of pyruvate kinase in the brain. Although the degree of phenylalanine inhibitory activity is similar in both fetal and adult cells, the enzymes in the fetal brain cells are significantly more vulnerable to inhibition than those in adult
658:
kinase deficiency. Over 250 PK-LR gene mutations have been identified and associated with pyruvate kinase deficiency. DNA testing has guided the discovery of the location of PKLR on chromosome 1 and the development of direct gene sequencing tests to molecularly diagnose pyruvate kinase deficiency.
657:
Pyruvate kinase deficiency is caused by an autosomal recessive trait. Mammals have two pyruvate kinase genes, PK-LR (which encodes for pyruvate kinase isozymes L and R) and PK-M (which encodes for pyruvate kinase isozyme M1), but only PKLR encodes for the red blood isozyme which effects pyruvate
599:
that regulates expression of the L isozyme of pyruvate kinase. A glucose-sensing module contains domains that are targets for regulatory phosphorylation based on the concentrations of glucose and cAMP, which then control its import into the nucleus. It may also be further activated by directly
498:
is the binding of an effector to a site on the protein other than the active site, causing a conformational change and altering the activity of that given protein or enzyme. Pyruvate kinase has been found to be allosterically activated by FBP and allosterically inactivated by ATP and alanine.
462:
reactions. Although it utilizes similar enzymes, gluconeogenesis is not the reverse of glycolysis. It is instead a pathway that circumvents the irreversible steps of glycolysis. Furthermore, gluconeogenesis and glycolysis do not occur concurrently in the cell at any given moment as they are
515:
because the higher the concentration of FBP, the greater the allosteric activation and magnitude of pyruvate kinase activity. Pyruvate kinase is most sensitive to the effects of FBP. As a result, the remainder of the regulatory mechanisms serve as secondary modification.
279:, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.
1157:
Ramseier TM, NĂšgre D, Cortay JC, Scarabel M, Cozzone AJ, Saier MH (November 1993). "In vitro binding of the pleiotropic transcriptional regulatory protein, FruR, to the fru, pps, ace, pts and icd operons of
Escherichia coli and Salmonella typhimurium".
696:
for cancer. The low activity dimer allows for build-up of phosphoenol pyruvate (PEP), leaving large concentrations of glycolytic intermediates for synthesis of biomolecules that will eventually be used by cancer cells. Phosphorylation of PKM2 by
511:. FBP binds to the allosteric binding site on domain C of pyruvate kinase and changes the conformation of the enzyme, causing the activation of pyruvate kinase activity. As an intermediate present within the glycolytic pathway, FBP provides
382:
of the glycolysis cycle, and may be one of the most ancient enzymes in all earth-based life. Phosphoenolpyruvate may have been present abiotically, and has been shown to be produced in high yield in a primitive triose glycolysis pathway.
3160:
524:
Covalent modifiers serve as indirect regulators by controlling the phosphorylation, dephosphorylation, acetylation, succinylation and oxidation of enzymes, resulting in the activation and inhibition of enzymatic activity. In the liver,
2411:
Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (March 2008). "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth".
449:
from pyruvate and other substrates. Gluconeogenesis utilizes noncarbohydrate sources to provide glucose to the brain and red blood cells in times of starvation when direct glucose reserves are exhausted. During
421:
This final step is highly regulated and deliberately irreversible because pyruvate is a crucial intermediate building block for further metabolic pathways. Once pyruvate is produced, it either enters the
3220:
2843:
2765:
463:
reciprocally regulated by cell signaling. Once the gluconeogenesis pathway is complete, the glucose produced is expelled from the liver, providing energy for the vital tissues in the fasting state.
291:
of pyruvate kinase expressed in vertebrates: L (liver), R (erythrocytes), M1 (muscle and brain) and M2 (early fetal tissue and most adult tissues). The L and R isozymes are expressed by the gene
356:, a step that is irreversible under physiological conditions. PykF is allosterically regulated by FBP which reflects the central position of PykF in cellular metabolism. PykF transcription in
897:
Eigenbrodt E, Reinacher M, Scheefers-Borchel U, Scheefers H, Friis R (1992-01-01). "Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells".
4397:
4511:
687:(PKU), showed elevated levels of phenylalanine and decreased effectiveness of PKM2. This inhibitory mechanism provides insight into the role of pyruvate kinase in brain cell damage.
303:(FBP), promoting the glycolytic pathway. The T-state, characterized by low substrate affinity, serves as the inactivated form of pyruvate kinase, bound and stabilized by ATP and
360:
is regulated by the global transcriptional regulator, Cra (FruR). PfkB was shown to be inhibited by MgATP at low concentrations of Fru-6P, and this regulation is important for
507:
FBP is the most significant source of regulation because it comes from within the glycolysis pathway. FBP is a glycolytic intermediate produced from the phosphorylation of
2354:
Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, Thomas CJ, Vander Heiden MG, Cantley LC (December 2011).
3871:
3894:
200:
4407:
3677:
1193:
Ramseier TM, Bledig S, Michotey V, Feghali R, Saier MH (June 1995). "The global regulatory protein FruR modulates the direction of carbon flow in
Escherichia coli".
3843:
4381:
322:
products of the M-gene (PKM1 contains exon 9 while PKM2 contains exon 10) and solely differ in 23 amino acids within a 56-amino acid stretch (aa 378-434) at their
4402:
4522:
4500:
604:
Once in the nucleus, its DNA binding domains activate pyruvate kinase transcription. Therefore, high glucose and low cAMP causes dephosphorylation of
2104:"Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein"
1430:
Bollenbach TJ, Nowak T (October 2001). "Kinetic linked-function analysis of the multiligand interactions on Mg(2+)-activated yeast pyruvate kinase".
2516:"Inhibition of human brain pyruvate kinase and hexokinase by phenylalanine and phenylpyruvate: possible relevance to phenylketonuric brain damage"
4486:
4318:
605:
592:
3101:
2941:
2879:
2801:
625:. In this condition, a lack of pyruvate kinase slows down the process of glycolysis. This effect is especially devastating in cells that lack
965:
Dombrauckas JD, Santarsiero BD, Mesecar AD (July 2005). "Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis".
219:
3278:
1715:"Distinguishing the interactions in the fructose 1,6-bisphosphate binding site of human liver pyruvate kinase that contribute to allostery"
1550:"Synergistic Allosteric Mechanism of Fructose-1,6-bisphosphate and Serine for Pyruvate Kinase M2 via Dynamics Fluctuation Network Analysis"
4533:
4461:
4428:
377:
There are two steps in the pyruvate kinase reaction in glycolysis. First, PEP transfers a phosphate group to ADP, producing ATP and the
3989:
4323:
3949:
2319:
Climent F, Roset F, Repiso A, PĂ©rez de la Ossa P (June 2009). "Red cell glycolytic enzyme disorders caused by mutations: an update".
4490:
3412:
2973:
569:
416:
The reaction catalyzed by pyruvate kinase is the final step of glycolysis. It is one of three rate-limiting steps of this pathway.
212:
1503:
Carbonell J, FelĂu JE, Marco R, Sols A (August 1973). "Pyruvate kinase. Classes of regulatory isoenzymes in mammalian tissues".
4129:
1487:
838:
163:
2708:
3256:
1989:"The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism"
4263:
2463:
Miller AL, Hawkins RA, Veech RL (March 1973). "Phenylketonuria: phenylalanine inhibits brain pyruvate kinase in vivo".
2223:
Richards, Paul; Ourabah, Sarah; Montagne, Jacques; Burnol, Anne-Françoise; Postic, Catherine; Guilmeau, Sandra (2017).
4589:
3833:
3627:
3477:
499:
Pyruvate Kinase tetramerization is promoted by FBP and Serine while tetramer dissociation is promoted by L-Cysteine.
352:). They catalyze the same reaction as in eukaryotes, namely the generation of ATP from ADP and PEP, the last step in
1848:"Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines"
1803:
Li YH, Li XF, Liu JT, Wang H, Fan LL, Li J, Sun GP (August 2018). "PKM2, a potential target for regulating cancer".
3974:
3271:
1656:"L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2"
2048:"Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2"
926:"The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing"
157:
3381:
2869:
139:
4745:
4547:
4542:
4102:
3920:
3346:
2791:
144:
458:
from being converted into pyruvate; instead, phosphoenolpyruvate is converted into glucose via a cascade of
4412:
4300:
4268:
4253:
2356:"Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses"
1010:"Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA"
4895:
3935:
3367:
3264:
717:
224:
1597:
Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, et al. (November 2012).
132:
4860:
3594:
2954:
2915:
2889:
1948:"Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes"
622:
3605:
2225:"MondoA/ChREBP: The usual suspects of transcriptional glucose sensing; Implication in pathophysiology"
4846:
4833:
4820:
4807:
4794:
4781:
4768:
4730:
3811:
3399:
3133:
2931:
2853:
756:
on two or more occasions. In some cases, the same organism will have both pyruvate kinase and PPDK.
484:
410:
300:
67:
409:
In yeast cells, the interaction of yeast pyruvate kinase (YPK) with PEP and its allosteric effector
389:
A simple diagram demonstrating the final step of glycolysis, the transfer of a phosphate group from
4740:
4694:
4637:
3998:
3979:
3910:
3764:
3644:
2701:
2680:
830:
753:
160:
50:
641:, which in a state of pyruvate kinase deficiency, rapidly become deficient in ATP and can undergo
471:
Glycolysis is highly regulated at three of its catalytic steps: the phosphorylation of glucose by
84:
4642:
3856:
3422:
3417:
3291:
3093:
3037:
3018:
1287:"Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA"
671:
455:
2575:"ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect"
4310:
4083:
3993:
3550:
3114:
3074:
2046:
Iqbal MA, Siddiqui FA, Gupta V, Chattopadhyay S, Gopinath P, Kumar B, et al. (July 2013).
1385:"Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis"
512:
402:
268:
4663:
4582:
4164:
4119:
3821:
3806:
3742:
3722:
3620:
3570:
3501:
3351:
3340:
2827:
1889:"Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes"
495:
417:
394:
260:
1654:
Nakatsu D, Horiuchi Y, Kano F, Noguchi Y, Sugawara T, Takamoto I, et al. (March 2015).
1328:"Phosphoenolpyruvate and Mg2+ binding to pyruvate kinase monitored by infrared spectroscopy"
822:
4735:
4078:
4073:
3953:
3816:
3796:
3705:
3525:
3472:
3286:
2811:
2676:
2624:"Reconstructing the mosaic glycolytic pathway of the anaerobic eukaryote Monocercomonoides"
2527:
2472:
2421:
2367:
2115:
2000:
1987:
Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR (February 2010).
1900:
1667:
1610:
1339:
630:
596:
508:
476:
319:
120:
8:
4900:
4699:
4341:
4333:
4114:
3781:
3717:
3681:
3185:
2775:
2694:
823:
601:
480:
390:
256:
96:
62:
2531:
2476:
2425:
2371:
2270:
Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B (September 2015).
2119:
2004:
1904:
1671:
1614:
1343:
55:
4632:
4204:
4142:
4093:
3828:
3655:
2651:
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2599:
2574:
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2445:
2388:
2355:
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2271:
2200:
2165:
2074:
2047:
2023:
1988:
1964:
1947:
1828:
1739:
1714:
1690:
1655:
1631:
1598:
1574:
1549:
1516:
1412:
1360:
1327:
1218:
1206:
1090:
1063:
1034:
1009:
990:
879:
798:
773:
2550:
2515:
1923:
1888:
1864:
1847:
1780:
1763:
1262:
1237:
942:
925:
175:
4890:
4219:
4209:
4199:
4124:
4108:
4067:
4053:
4048:
3786:
3749:
2720:
2656:
2604:
2555:
2488:
2437:
2393:
2336:
2301:
2252:
2244:
2205:
2187:
2143:
2138:
2103:
2079:
2028:
1969:
1928:
1869:
1832:
1820:
1785:
1744:
1695:
1636:
1579:
1530:
1483:
1476:
1447:
1416:
1404:
1365:
1308:
1267:
1253:
1210:
1175:
1139:
1095:
1039:
982:
947:
906:
871:
834:
803:
422:
151:
2500:
2449:
1222:
994:
4678:
4673:
4647:
4575:
4552:
4214:
4194:
4136:
4032:
3930:
3915:
3861:
3759:
3754:
3613:
3463:
2860:
2782:
2646:
2638:
2594:
2586:
2545:
2535:
2480:
2429:
2383:
2375:
2328:
2291:
2283:
2236:
2195:
2177:
2133:
2123:
2069:
2059:
2018:
2008:
1959:
1918:
1908:
1859:
1812:
1775:
1734:
1726:
1685:
1675:
1626:
1618:
1569:
1561:
1520:
1512:
1439:
1396:
1355:
1347:
1298:
1257:
1249:
1202:
1167:
1129:
1116:
Valentini G, Chiarelli L, Fortin R, Speranza ML, Galizzi A, Mattevi A (June 2000).
1085:
1075:
1064:"Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer"
1029:
1021:
974:
937:
883:
863:
793:
785:
646:
577:
534:
336:
35:
2622:
Liapounova NA, Hampl V, Gordon PM, Sensen CW, Gedamu L, Dacks JB (December 2006).
2240:
1025:
340:, have two isoforms of pyruvate kinase, PykA and PykF, which are 37% identical in
28:
4725:
4709:
4622:
4475:
4465:
4287:
4258:
3884:
3776:
3545:
3299:
2484:
1384:
684:
638:
459:
442:
361:
252:
275:) before it was recognized that it did not directly catalyze phosphorylation of
271:. Pyruvate kinase was inappropriately named (inconsistently with a conventional
179:
4874:
4763:
4704:
4443:
4282:
4189:
4181:
4058:
4021:
2964:
2922:
2686:
2520:
Proceedings of the
National Academy of Sciences of the United States of America
2332:
2108:
Proceedings of the
National Academy of Sciences of the United States of America
1993:
Proceedings of the
National Academy of Sciences of the United States of America
1893:
Proceedings of the
National Academy of Sciences of the United States of America
1816:
1660:
Proceedings of the
National Academy of Sciences of the United States of America
1351:
703:
195:
2818:
4884:
4668:
4627:
3712:
3516:
3124:
3028:
2248:
2191:
2182:
1762:
Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL (February 1998).
1565:
1303:
1286:
896:
730:
451:
378:
170:
2379:
2064:
2013:
1680:
1080:
4617:
3801:
3771:
3700:
3233:
3195:
2896:
2660:
2608:
2540:
2441:
2397:
2340:
2305:
2256:
2224:
2209:
2147:
2128:
2083:
2032:
1913:
1824:
1764:"The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate"
1748:
1699:
1640:
1599:"Serine is a natural ligand and allosteric activator of pyruvate kinase M2"
1583:
1451:
1408:
1369:
1171:
1143:
1134:
1117:
1099:
1043:
986:
807:
626:
546:
425:
for further production of ATP under aerobic conditions, or is converted to
2573:
Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, et al. (December 2012).
2559:
2492:
1973:
1789:
1534:
1312:
1271:
1214:
1179:
951:
910:
875:
4841:
4776:
4612:
4367:
4357:
3958:
3695:
3636:
3488:
3336:
1932:
1873:
748:
645:. Therefore, pyruvate kinase deficiency can cause chronic nonspherocytic
587:
530:
426:
349:
345:
3084:
2642:
2433:
1622:
108:
4169:
4012:
3925:
3690:
3640:
3635:
3492:
3393:
3389:
3385:
3320:
3295:
3287:
2749:
2717:
1525:
1400:
867:
472:
353:
323:
244:
2410:
2287:
1730:
1443:
1238:"The catabolite repressor/activator (Cra) protein of enteric bacteria"
978:
683:
brain cells. A study of PKM2 in babies with the genetic brain disease
4815:
4789:
4448:
4361:
3898:
3664:
742:
725:
642:
634:
608:, which then upregulates expression of pyruvate kinase in the liver.
558:
2590:
789:
4869:
4295:
3875:
3536:
721:
581:
526:
454:, pyruvate kinase is inhibited, thus preventing the "leak-down" of
398:
276:
264:
248:
2318:
2102:
Kawaguchi T, Takenoshita M, Kabashima T, Uyeda K (November 2001).
2101:
385:
4398:
CDP-diacylglycerolâglycerol-3-phosphate 3-phosphatidyltransferase
4246:
4231:
3847:
3512:
3427:
3139:
2740:
2733:
736:
573:
446:
430:
304:
288:
127:
2353:
1115:
4828:
4598:
4224:
3659:
3587:
3583:
3579:
3575:
3302:
2045:
315:
272:
240:
207:
103:
91:
79:
2166:"Carbohydrate Sensing Through the Transcription Factor ChREBP"
487:(FBP), which serves as an allosteric effector for the enzyme.
4802:
4241:
4236:
4088:
2222:
1945:
1192:
964:
697:
661:
2272:"Erythrocyte pyruvate kinase deficiency: 2015 status report"
4152:
4147:
4043:
4038:
3737:
3732:
3727:
3440:
3436:
3363:
3359:
3355:
2621:
1986:
1596:
1156:
1061:
666:
311:
296:
295:, whereas the M1 and M2 isozymes are expressed by the gene
292:
115:
4567:
3243:
1653:
854:
Muirhead H (April 1990). "Isoenzymes of pyruvate kinase".
621:
Genetic defects of this enzyme cause the disease known as
3332:
3328:
3324:
2321:
Cardiovascular & Hematological
Disorders Drug Targets
2269:
1548:
Yang J, Liu H, Liu X, Gu C, Luo R, Chen HF (June 2016).
1473:
436:
1502:
1111:
1109:
441:
Pyruvate kinase also serves as a regulatory enzyme for
707:
Distribution of red blood cell abnormalities worldwide
588:
Carbohydrate response element binding protein (ChREBP)
4858:
4408:
CDP-diacylglycerolâinositol 3-phosphatidyltransferase
1946:
Argaud D, Roth H, Wiernsperger N, Leverve XM (1993).
1761:
774:"Human pyruvate kinase M2: a multifunctional protein"
445:, a biochemical pathway in which the liver generates
4413:
CDP-diacylglycerolâcholine O-phosphatidyltransferase
1106:
1062:
Prakasam G, Iqbal MA, Bamezai RN, Mazurek S (2018).
4403:
CDP-diacylglycerolâserine O-phosphatidyltransferase
2163:
576:up-regulate expression of PKM2 while hormones like
397:(ADP) by pyruvate kinase, yielding one molecule of
2462:
1475:
1474:Berg JM, Tymoczko JL, Stryer J, Clarke ND (2002).
923:
724:and has been transferred to a number of anaerobic
3571:Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
552:
4882:
2716:
2164:Ortega-Prieto, Paula; Postic, Catherine (2019).
1429:
1284:
1007:
2572:
1482:(fifth ed.). New York, NY: W.H. Freeman.
1118:"The allosteric regulation of pyruvate kinase"
4583:
3621:
3272:
2702:
1382:
1235:
924:Noguchi T, Inoue H, Tanaka T (October 1986).
716:A reversible enzyme with a similar function,
1886:
1845:
1554:Journal of Chemical Information and Modeling
1547:
1469:
1467:
1465:
1463:
1461:
1285:Sabnis NA, Yang H, Romeo T (December 1995).
1008:Chen M, Zhang J, Manley JL (November 2010).
771:
690:
502:
4429:N-acetylglucosamine-1-phosphate transferase
4319:UTPâglucose-1-phosphate uridylyltransferase
1939:
1802:
677:
633:as their sole source of energy because the
4590:
4576:
3628:
3614:
3279:
3265:
2709:
2695:
1880:
1325:
662:Applications of pyruvate kinase inhibition
282:
27:
4523:serine/threonine-specific protein kinases
4501:serine/threonine-specific protein kinases
4324:Galactose-1-phosphate uridylyltransferase
2679:at the U.S. National Library of Medicine
2650:
2598:
2549:
2539:
2387:
2295:
2199:
2181:
2137:
2127:
2073:
2063:
2022:
2012:
1963:
1922:
1912:
1863:
1779:
1738:
1689:
1679:
1630:
1573:
1524:
1458:
1359:
1302:
1261:
1133:
1089:
1079:
1033:
941:
797:
3413:Glyceraldehyde 3-phosphate dehydrogenase
853:
702:
667:Reactive Oxygen Species (ROS) Inhibition
611:
384:
820:
490:
329:
4883:
1712:
652:
4571:
3609:
3260:
2690:
2513:
2229:Metabolism: Clinical and Experimental
2159:
2157:
2097:
2095:
2093:
1846:Birnbaum MJ, Fain JN (January 1977).
1057:
1055:
1053:
772:Gupta V, Bamezai RN (November 2010).
519:
437:Gluconeogenesis: the reverse reaction
1383:Coggins AJ, Powner MW (April 2017).
570:Heterogenous ribonucleotide proteins
1852:The Journal of Biological Chemistry
1291:The Journal of Biological Chemistry
1236:Saier MH, Ramseier TM (June 1996).
1122:The Journal of Biological Chemistry
930:The Journal of Biological Chemistry
540:
334:Many Enterobacteriaceae, including
13:
2154:
2090:
1965:10.1111/j.1432-1033.1993.tb17886.x
1517:10.1111/j.1432-1033.1973.tb02969.x
1207:10.1111/j.1365-2958.1995.tb02339.x
1050:
829:(4th ed.). Elsevier. p.
698:Mitogen-activated protein kinase 1
564:
14:
4912:
3834:Glucose-1,6-bisphosphate synthase
3478:Phosphoenolpyruvate carboxykinase
2670:
1887:FeliĂș JE, Hue L, Hers HG (1976).
847:
33:3D structure of pyruvate kinase (
4868:
3975:Ribose-phosphate diphosphokinase
3242:
3219:
3194:
3159:
3123:
3100:
3083:
3052:
3027:
2993:
2963:
2940:
2921:
2895:
2878:
2859:
2842:
2817:
2800:
2781:
2764:
2739:
1952:European Journal of Biochemistry
1505:European Journal of Biochemistry
1254:10.1128/jb.178.12.3411-3417.1996
856:Biochemical Society Transactions
263:(ADP), yielding one molecule of
2615:
2566:
2507:
2456:
2404:
2347:
2312:
2263:
2216:
2039:
1980:
1839:
1796:
1755:
1706:
1647:
1590:
1541:
1496:
1423:
1376:
1319:
1278:
1229:
1186:
1150:
899:Critical Reviews in Oncogenesis
711:
637:is not available. For example,
629:, because these cells must use
3382:Fructose-bisphosphate aldolase
2276:American Journal of Hematology
1001:
958:
917:
890:
814:
765:
553:Inhibitory effect of metformin
318:. PKM1 and PKM2 are different
1:
4548:Protein-histidine tele-kinase
4543:Protein-histidine pros-kinase
4422:Glycosyl-1-phosphotransferase
2241:10.1016/j.metabol.2017.01.033
1865:10.1016/S0021-9258(17)32749-7
1781:10.1016/S0969-2126(98)00021-5
1713:Ishwar A (24 February 2015).
1326:Kumar S, Barth A (May 2010).
1026:10.1158/0008-5472.CAN-10-2513
943:10.1016/S0021-9258(18)67091-7
759:
616:
584:aid in down-regulating PKM2.
466:
372:
243:involved in the last step of
4254:RNA-dependent RNA polymerase
2485:10.1126/science.179.4076.904
1160:Journal of Molecular Biology
433:under anaerobic conditions.
310:The PKM gene consists of 12
7:
4597:
4161:RNA-directed DNA polymerase
4029:DNA-directed DNA polymerase
3368:Fructose 1,6-bisphosphatase
825:Basic Medical Endocrinology
718:pyruvate phosphate dikinase
367:
10:
4917:
4514:: protein-dual-specificity
3595:Bisphosphoglycerate mutase
2974:Glyceraldehyde-3-phosphate
2955:Glyceraldehyde 3-phosphate
2916:Glyceraldehyde 3-phosphate
2890:Dihydroxyacetone phosphate
2333:10.2174/187152909788488636
1817:10.1016/j.gene.2018.05.038
1352:10.1016/j.bpj.2009.12.4335
623:pyruvate kinase deficiency
4754:
4746:MichaelisâMenten kinetics
4718:
4687:
4656:
4605:
4532:
4510:
4485:
4460:
4441:
4421:
4390:
4380:
4350:
4332:
4309:
4281:
4180:
4020:
4011:
3988:
3948:
3893:
3870:
3842:
3676:
3652:
3563:
3534:
3510:
3486:
3461:
3454:
3408:
3400:Triosephosphate isomerase
3377:
3316:
3309:
2854:Fructose 1,6-bisphosphate
2727:
720:(PPDK), is found in some
691:Pyruvate Kinase in Cancer
503:Fructose-1,6-bisphosphate
485:fructose-1,6-bisphosphate
475:, the phosphorylation of
411:Fructose 1,6-bisphosphate
301:fructose 1,6-bisphosphate
218:
206:
194:
189:
185:
169:
150:
138:
126:
114:
102:
90:
78:
73:
61:
49:
44:
26:
21:
4638:Diffusion-limited enzyme
4491:protein-serine/threonine
4391:Phosphatidyltransferases
3980:Thiamine diphosphokinase
2681:Medical Subject Headings
2183:10.3389/fgene.2019.00472
1566:10.1021/acs.jcim.6b00115
1304:10.1074/jbc.270.49.29096
754:horizontal gene transfer
678:Phenylalanine inhibition
3423:Phosphoglycerate mutase
3418:Phosphoglycerate kinase
3292:carbohydrate metabolism
3094:Phosphoglycerate mutase
3038:Phosphoglycerate kinase
3019:1,3-Bisphosphoglycerate
2514:Weber G (August 1969).
2380:10.1126/science.1211485
2065:10.1186/1476-4598-12-72
2014:10.1073/pnas.0914845107
1681:10.1073/pnas.1417197112
1242:Journal of Bacteriology
1081:10.3389/fonc.2018.00022
672:Reactive oxygen species
513:feedforward stimulation
283:Isozymes in vertebrates
4311:Nucleotidyltransferase
3994:nucleotidyltransferase
3921:Nucleoside-diphosphate
3551:Glycerol dehydrogenase
2541:10.1073/pnas.63.4.1365
2129:10.1073/pnas.231370798
1914:10.1073/pnas.73.8.2762
1195:Molecular Microbiology
1172:10.1006/jmbi.1993.1561
1135:10.1074/jbc.M001870200
708:
545:In order to prevent a
406:
4731:EadieâHofstee diagram
4664:Allosteric regulation
4165:Reverse transcriptase
3502:Lactate dehydrogenase
3352:Phosphofructokinase 1
3341:Glucose 6-phosphatase
2870:Fructose-bisphosphate
2828:Phosphofructokinase-1
2170:Frontiers in Genetics
1068:Frontiers in Oncology
728:groups (for example,
706:
612:Clinical applications
496:Allosteric regulation
395:adenosine diphosphate
388:
261:adenosine diphosphate
4741:LineweaverâBurk plot
3954:diphosphotransferase
3936:Thiamine-diphosphate
3643:-containing groups (
3526:Alanine transaminase
3473:Pyruvate carboxylase
3455:Gluconeogenesis only
2812:Fructose 6-phosphate
631:anaerobic glycolysis
602:glucose-6-phosphate.
597:transcription factor
509:fructose 6-phosphate
491:Allosteric effectors
477:fructose-6-phosphate
401:and one molecule of
330:Isozymes in bacteria
267:and one molecule of
4536:: protein-histidine
4454:; protein acceptor)
4342:mRNA capping enzyme
4334:Guanylyltransferase
3186:Phosphoenolpyruvate
2792:Glucose-6-phosphate
2776:Glucose 6-phosphate
2643:10.1128/EC.00258-06
2579:Nature Cell Biology
2532:1969PNAS...63.1365W
2477:1973Sci...179..904M
2434:10.1038/nature06734
2426:2008Natur.452..230C
2372:2011Sci...334.1278A
2120:2001PNAS...9813710K
2005:2010PNAS..107.1894C
1905:1976PNAS...73.2762F
1672:2015PNAS..112E1067N
1623:10.1038/nature11540
1615:2012Natur.491..458C
1344:2010BpJ....98.1931K
1332:Biophysical Journal
821:Goodman HM (2009).
653:PK-LR gene mutation
481:phosphofructokinase
456:phosphoenolpyruvate
418:Rate-limiting steps
391:phosphoenolpyruvate
257:phosphoenolpyruvate
4896:Glycolysis enzymes
4700:Enzyme superfamily
4633:Enzyme promiscuity
3812:Phosphoinositide 3
3656:phosphotransferase
3241:
3232:
3193:
3184:
3122:
3115:2-Phosphoglycerate
3113:
3082:
3075:3-Phosphoglycerate
3073:
3026:
3017:
2962:
2953:
1401:10.1038/nchem.2624
868:10.1042/bst0180193
709:
520:Covalent modifiers
407:
251:the transfer of a
4856:
4855:
4565:
4564:
4561:
4560:
4437:
4436:
4376:
4375:
4277:
4276:
4190:Template-directed
3944:
3943:
3911:Phosphomevalonate
3603:
3602:
3559:
3558:
3450:
3449:
3347:Glucose isomerase
3254:
3253:
3239:
3230:
3191:
3182:
3120:
3111:
3080:
3071:
3024:
3015:
2960:
2951:
2721:metabolic pathway
2366:(6060): 1278â83.
2288:10.1002/ajh.24088
1731:10.1021/bi501426w
1609:(7424): 458â462.
1489:978-0-7167-3051-4
1444:10.1021/bi010126o
1438:(43): 13097â106.
1297:(49): 29096â104.
979:10.1021/bi0474923
840:978-0-12-373975-9
578:tri-iodothyronine
559:dimethylbiguanide
234:
233:
230:
229:
133:metabolic pathway
4908:
4873:
4872:
4864:
4736:HanesâWoolf plot
4679:Enzyme activator
4674:Enzyme inhibitor
4648:Enzyme catalysis
4592:
4585:
4578:
4569:
4568:
4553:Histidine kinase
4476:tyrosine kinases
4466:protein-tyrosine
4458:
4457:
4388:
4387:
4195:RNA polymerase I
4018:
4017:
4009:
4008:
3862:Aspartate kinase
3857:Phosphoglycerate
3674:
3673:
3630:
3623:
3616:
3607:
3606:
3459:
3458:
3314:
3313:
3281:
3274:
3267:
3258:
3257:
3246:
3223:
3198:
3163:
3127:
3104:
3087:
3056:
3031:
2997:
2967:
2944:
2925:
2899:
2882:
2863:
2846:
2821:
2804:
2785:
2768:
2743:
2711:
2704:
2697:
2688:
2687:
2665:
2664:
2654:
2628:
2627:(Free full text)
2619:
2613:
2612:
2602:
2585:(12): 1295â304.
2570:
2564:
2563:
2553:
2543:
2511:
2505:
2504:
2460:
2454:
2453:
2408:
2402:
2401:
2391:
2351:
2345:
2344:
2316:
2310:
2309:
2299:
2267:
2261:
2260:
2220:
2214:
2213:
2203:
2185:
2161:
2152:
2151:
2141:
2131:
2099:
2088:
2087:
2077:
2067:
2052:Molecular Cancer
2043:
2037:
2036:
2026:
2016:
1984:
1978:
1977:
1967:
1943:
1937:
1936:
1926:
1916:
1884:
1878:
1877:
1867:
1843:
1837:
1836:
1800:
1794:
1793:
1783:
1759:
1753:
1752:
1742:
1710:
1704:
1703:
1693:
1683:
1666:(10): E1067-76.
1651:
1645:
1644:
1634:
1594:
1588:
1587:
1577:
1560:(6): 1184â1192.
1545:
1539:
1538:
1528:
1500:
1494:
1493:
1481:
1471:
1456:
1455:
1427:
1421:
1420:
1389:Nature Chemistry
1380:
1374:
1373:
1363:
1323:
1317:
1316:
1306:
1282:
1276:
1275:
1265:
1233:
1227:
1226:
1190:
1184:
1183:
1154:
1148:
1147:
1137:
1128:(24): 18145â52.
1113:
1104:
1103:
1093:
1083:
1059:
1048:
1047:
1037:
1005:
999:
998:
962:
956:
955:
945:
936:(29): 13807â12.
921:
915:
914:
894:
888:
887:
851:
845:
844:
828:
818:
812:
811:
801:
769:
752:), it seems via
685:phenylketonurics
647:hemolytic anemia
541:Hormonal control
535:protein kinase A
324:carboxy terminus
187:
186:
38:
31:
19:
18:
16:Class of enzymes
4916:
4915:
4911:
4910:
4909:
4907:
4906:
4905:
4881:
4880:
4879:
4867:
4859:
4857:
4852:
4764:Oxidoreductases
4750:
4726:Enzyme kinetics
4714:
4710:List of enzymes
4683:
4652:
4623:Catalytic triad
4601:
4596:
4566:
4557:
4528:
4506:
4481:
4452:
4446:
4442:2.7.10-2.7.13:
4433:
4417:
4384:: miscellaneous
4372:
4346:
4328:
4305:
4288:exoribonuclease
4285:
4273:
4259:Polyadenylation
4176:
4002:
3996:
3984:
3966:
3962:
3956:
3940:
3902:
3889:
3866:
3838:
3668:
3662:
3654:
3648:
3634:
3604:
3599:
3555:
3546:Glycerol kinase
3530:
3506:
3482:
3446:
3433:Pyruvate kinase
3404:
3373:
3305:
3300:gluconeogenesis
3285:
3255:
3250:
3249:
3248:
3247:
3237:
3226:
3225:
3224:
3216:
3215:
3212:
3208:
3205:Pyruvate kinase
3200:
3199:
3189:
3178:
3177:
3176:
3174:
3169:
3165:
3164:
3156:
3155:
3153:
3148:
3144:
3135:
3134:Phosphopyruvate
3129:
3128:
3118:
3107:
3106:
3105:
3097:
3089:
3088:
3078:
3067:
3066:
3065:
3062:
3058:
3057:
3049:
3048:
3045:
3041:
3033:
3032:
3022:
3011:
3010:
3009:
3006:
3005:
2999:
2998:
2990:
2989:
2986:
2985:
2979:
2975:
2969:
2968:
2958:
2947:
2946:
2945:
2937:
2933:
2932:Triosephosphate
2927:
2926:
2919:
2911:
2910:
2907:
2901:
2900:
2893:
2885:
2884:
2883:
2875:
2871:
2865:
2864:
2857:
2849:
2848:
2847:
2839:
2838:
2835:
2831:
2823:
2822:
2815:
2807:
2806:
2805:
2797:
2793:
2787:
2786:
2779:
2771:
2770:
2769:
2761:
2760:
2757:
2753:
2745:
2744:
2737:
2723:
2715:
2677:Pyruvate+kinase
2673:
2668:
2637:(12): 2138â46.
2631:Eukaryotic Cell
2626:
2620:
2616:
2591:10.1038/ncb2629
2571:
2567:
2512:
2508:
2471:(4076): 904â6.
2461:
2457:
2420:(7184): 230â3.
2409:
2405:
2352:
2348:
2317:
2313:
2268:
2264:
2221:
2217:
2162:
2155:
2114:(24): 13710â5.
2100:
2091:
2044:
2040:
1985:
1981:
1944:
1940:
1885:
1881:
1844:
1840:
1801:
1797:
1760:
1756:
1711:
1707:
1652:
1648:
1595:
1591:
1546:
1542:
1501:
1497:
1490:
1472:
1459:
1428:
1424:
1381:
1377:
1324:
1320:
1283:
1279:
1234:
1230:
1191:
1187:
1155:
1151:
1114:
1107:
1060:
1051:
1020:(22): 8977â80.
1014:Cancer Research
1006:
1002:
973:(27): 9417â29.
963:
959:
922:
918:
905:(1â2): 91â115.
895:
891:
852:
848:
841:
819:
815:
790:10.1002/pro.505
784:(11): 2031â44.
778:Protein Science
770:
766:
762:
714:
693:
680:
669:
664:
655:
639:red blood cells
619:
614:
590:
567:
565:Gene Regulation
555:
543:
522:
505:
493:
469:
460:gluconeogenesis
443:gluconeogenesis
439:
375:
370:
362:gluconeogenesis
332:
285:
253:phosphate group
237:Pyruvate kinase
40:
34:
22:Pyruvate kinase
17:
12:
11:
5:
4914:
4904:
4903:
4898:
4893:
4878:
4877:
4854:
4853:
4851:
4850:
4837:
4824:
4811:
4798:
4785:
4772:
4758:
4756:
4752:
4751:
4749:
4748:
4743:
4738:
4733:
4728:
4722:
4720:
4716:
4715:
4713:
4712:
4707:
4702:
4697:
4691:
4689:
4688:Classification
4685:
4684:
4682:
4681:
4676:
4671:
4666:
4660:
4658:
4654:
4653:
4651:
4650:
4645:
4640:
4635:
4630:
4625:
4620:
4615:
4609:
4607:
4603:
4602:
4595:
4594:
4587:
4580:
4572:
4563:
4562:
4559:
4558:
4556:
4555:
4550:
4545:
4539:
4537:
4530:
4529:
4527:
4526:
4517:
4515:
4508:
4507:
4505:
4504:
4495:
4493:
4483:
4482:
4480:
4479:
4470:
4468:
4455:
4450:
4444:protein kinase
4439:
4438:
4435:
4434:
4432:
4431:
4425:
4423:
4419:
4418:
4416:
4415:
4410:
4405:
4400:
4394:
4392:
4385:
4378:
4377:
4374:
4373:
4371:
4370:
4365:
4354:
4352:
4348:
4347:
4345:
4344:
4338:
4336:
4330:
4329:
4327:
4326:
4321:
4315:
4313:
4307:
4306:
4304:
4303:
4298:
4292:
4290:
4283:Phosphorolytic
4279:
4278:
4275:
4274:
4272:
4271:
4266:
4261:
4256:
4251:
4250:
4249:
4244:
4239:
4229:
4228:
4227:
4217:
4212:
4207:
4202:
4197:
4192:
4186:
4184:
4182:RNA polymerase
4178:
4177:
4175:
4174:
4173:
4172:
4162:
4158:
4157:
4156:
4155:
4150:
4145:
4134:
4133:
4132:
4127:
4122:
4117:
4106:
4100:
4099:
4098:
4091:
4086:
4081:
4076:
4065:
4064:
4063:
4056:
4051:
4046:
4041:
4030:
4026:
4024:
4022:DNA polymerase
4015:
4006:
4000:
3986:
3985:
3983:
3982:
3977:
3971:
3969:
3964:
3960:
3946:
3945:
3942:
3941:
3939:
3938:
3933:
3928:
3923:
3918:
3913:
3907:
3905:
3900:
3891:
3890:
3888:
3887:
3881:
3879:
3868:
3867:
3865:
3864:
3859:
3853:
3851:
3840:
3839:
3837:
3836:
3831:
3826:
3825:
3824:
3819:
3809:
3807:Diacylglycerol
3804:
3799:
3794:
3789:
3784:
3779:
3774:
3769:
3768:
3767:
3757:
3752:
3747:
3746:
3745:
3740:
3735:
3730:
3725:
3718:Phosphofructo-
3715:
3710:
3709:
3708:
3698:
3693:
3687:
3685:
3671:
3666:
3650:
3649:
3633:
3632:
3625:
3618:
3610:
3601:
3600:
3598:
3597:
3592:
3591:
3590:
3567:
3565:
3561:
3560:
3557:
3556:
3554:
3553:
3548:
3542:
3540:
3532:
3531:
3529:
3528:
3522:
3520:
3508:
3507:
3505:
3504:
3498:
3496:
3484:
3483:
3481:
3480:
3475:
3469:
3467:
3456:
3452:
3451:
3448:
3447:
3445:
3444:
3430:
3425:
3420:
3415:
3409:
3406:
3405:
3403:
3402:
3397:
3378:
3375:
3374:
3372:
3371:
3349:
3344:
3317:
3311:
3307:
3306:
3284:
3283:
3276:
3269:
3261:
3252:
3251:
3240:2 Ă
3238:
3228:
3227:
3218:
3217:
3213:
3210:
3209:
3202:
3201:
3192:2 Ă
3190:
3180:
3179:
3172:
3170:
3167:
3166:
3158:
3157:
3151:
3149:
3146:
3145:
3131:
3130:
3121:2 Ă
3119:
3109:
3108:
3099:
3098:
3091:
3090:
3081:2 Ă
3079:
3069:
3068:
3063:
3060:
3059:
3051:
3050:
3046:
3043:
3042:
3035:
3034:
3025:2 Ă
3023:
3013:
3012:
3007:
3003:
3001:
3000:
2992:
2991:
2987:
2983:
2981:
2980:
2971:
2970:
2961:2 Ă
2959:
2949:
2948:
2939:
2938:
2929:
2928:
2920:
2913:
2912:
2908:
2903:
2902:
2894:
2887:
2886:
2877:
2876:
2867:
2866:
2858:
2851:
2850:
2841:
2840:
2836:
2833:
2832:
2825:
2824:
2816:
2809:
2808:
2799:
2798:
2789:
2788:
2780:
2773:
2772:
2763:
2762:
2758:
2755:
2754:
2747:
2746:
2738:
2731:
2730:
2729:
2728:
2725:
2724:
2714:
2713:
2706:
2699:
2691:
2685:
2684:
2672:
2671:External links
2669:
2667:
2666:
2614:
2565:
2506:
2455:
2403:
2346:
2311:
2262:
2215:
2153:
2089:
2038:
1979:
1938:
1879:
1838:
1795:
1774:(2): 195â210.
1754:
1725:(7): 1516â24.
1705:
1646:
1589:
1540:
1495:
1488:
1457:
1422:
1395:(4): 310â317.
1375:
1338:(9): 1931â40.
1318:
1277:
1248:(12): 3411â7.
1228:
1201:(6): 1157â69.
1185:
1149:
1105:
1049:
1000:
957:
916:
889:
846:
839:
813:
763:
761:
758:
713:
710:
692:
689:
679:
676:
668:
665:
663:
660:
654:
651:
618:
615:
613:
610:
589:
586:
566:
563:
557:Metformin, or
554:
551:
542:
539:
521:
518:
504:
501:
492:
489:
468:
465:
438:
435:
374:
371:
369:
366:
331:
328:
284:
281:
232:
231:
228:
227:
222:
216:
215:
210:
204:
203:
198:
192:
191:
183:
182:
173:
167:
166:
155:
148:
147:
142:
136:
135:
130:
124:
123:
118:
112:
111:
106:
100:
99:
94:
88:
87:
82:
76:
75:
71:
70:
65:
59:
58:
53:
47:
46:
42:
41:
32:
24:
23:
15:
9:
6:
4:
3:
2:
4913:
4902:
4899:
4897:
4894:
4892:
4889:
4888:
4886:
4876:
4871:
4866:
4865:
4862:
4848:
4844:
4843:
4838:
4835:
4831:
4830:
4825:
4822:
4818:
4817:
4812:
4809:
4805:
4804:
4799:
4796:
4792:
4791:
4786:
4783:
4779:
4778:
4773:
4770:
4766:
4765:
4760:
4759:
4757:
4753:
4747:
4744:
4742:
4739:
4737:
4734:
4732:
4729:
4727:
4724:
4723:
4721:
4717:
4711:
4708:
4706:
4705:Enzyme family
4703:
4701:
4698:
4696:
4693:
4692:
4690:
4686:
4680:
4677:
4675:
4672:
4670:
4669:Cooperativity
4667:
4665:
4662:
4661:
4659:
4655:
4649:
4646:
4644:
4641:
4639:
4636:
4634:
4631:
4629:
4628:Oxyanion hole
4626:
4624:
4621:
4619:
4616:
4614:
4611:
4610:
4608:
4604:
4600:
4593:
4588:
4586:
4581:
4579:
4574:
4573:
4570:
4554:
4551:
4549:
4546:
4544:
4541:
4540:
4538:
4535:
4531:
4525:
4524:
4519:
4518:
4516:
4513:
4509:
4503:
4502:
4497:
4496:
4494:
4492:
4488:
4484:
4478:
4477:
4472:
4471:
4469:
4467:
4463:
4459:
4456:
4453:
4445:
4440:
4430:
4427:
4426:
4424:
4420:
4414:
4411:
4409:
4406:
4404:
4401:
4399:
4396:
4395:
4393:
4389:
4386:
4383:
4379:
4369:
4366:
4363:
4359:
4356:
4355:
4353:
4349:
4343:
4340:
4339:
4337:
4335:
4331:
4325:
4322:
4320:
4317:
4316:
4314:
4312:
4308:
4302:
4299:
4297:
4294:
4293:
4291:
4289:
4284:
4280:
4270:
4267:
4265:
4262:
4260:
4257:
4255:
4252:
4248:
4245:
4243:
4240:
4238:
4235:
4234:
4233:
4230:
4226:
4223:
4222:
4221:
4218:
4216:
4213:
4211:
4208:
4206:
4203:
4201:
4198:
4196:
4193:
4191:
4188:
4187:
4185:
4183:
4179:
4171:
4168:
4167:
4166:
4163:
4160:
4159:
4154:
4151:
4149:
4146:
4144:
4141:
4140:
4138:
4135:
4131:
4128:
4126:
4123:
4121:
4118:
4116:
4113:
4112:
4110:
4107:
4104:
4101:
4097:
4096:
4092:
4090:
4087:
4085:
4082:
4080:
4077:
4075:
4072:
4071:
4069:
4066:
4062:
4061:
4057:
4055:
4052:
4050:
4047:
4045:
4042:
4040:
4037:
4036:
4034:
4031:
4028:
4027:
4025:
4023:
4019:
4016:
4014:
4010:
4007:
4004:
3995:
3991:
3987:
3981:
3978:
3976:
3973:
3972:
3970:
3967:
3955:
3951:
3947:
3937:
3934:
3932:
3929:
3927:
3924:
3922:
3919:
3917:
3914:
3912:
3909:
3908:
3906:
3903:
3896:
3892:
3886:
3883:
3882:
3880:
3877:
3873:
3869:
3863:
3860:
3858:
3855:
3854:
3852:
3849:
3845:
3841:
3835:
3832:
3830:
3827:
3823:
3822:Class II PI 3
3820:
3818:
3815:
3814:
3813:
3810:
3808:
3805:
3803:
3800:
3798:
3797:Deoxycytidine
3795:
3793:
3790:
3788:
3785:
3783:
3780:
3778:
3775:
3773:
3770:
3766:
3765:ADP-thymidine
3763:
3762:
3761:
3758:
3756:
3753:
3751:
3748:
3744:
3741:
3739:
3736:
3734:
3731:
3729:
3726:
3724:
3721:
3720:
3719:
3716:
3714:
3711:
3707:
3704:
3703:
3702:
3699:
3697:
3694:
3692:
3689:
3688:
3686:
3683:
3679:
3675:
3672:
3669:
3661:
3657:
3651:
3646:
3642:
3638:
3631:
3626:
3624:
3619:
3617:
3612:
3611:
3608:
3596:
3593:
3589:
3585:
3581:
3577:
3574:
3573:
3572:
3569:
3568:
3566:
3562:
3552:
3549:
3547:
3544:
3543:
3541:
3538:
3533:
3527:
3524:
3523:
3521:
3518:
3517:Alanine cycle
3514:
3509:
3503:
3500:
3499:
3497:
3494:
3490:
3485:
3479:
3476:
3474:
3471:
3470:
3468:
3465:
3460:
3457:
3453:
3442:
3438:
3434:
3431:
3429:
3426:
3424:
3421:
3419:
3416:
3414:
3411:
3410:
3407:
3401:
3398:
3395:
3391:
3387:
3383:
3380:
3379:
3376:
3369:
3365:
3361:
3357:
3353:
3350:
3348:
3345:
3342:
3338:
3334:
3330:
3326:
3322:
3319:
3318:
3315:
3312:
3308:
3304:
3301:
3297:
3293:
3289:
3282:
3277:
3275:
3270:
3268:
3263:
3262:
3259:
3245:
3236:
3235:
3222:
3207:
3206:
3197:
3188:
3187:
3162:
3143:
3141:
3137:
3126:
3117:
3116:
3103:
3096:
3095:
3086:
3077:
3076:
3055:
3040:
3039:
3030:
3021:
3020:
2996:
2978:
2977:
2976:dehydrogenase
2966:
2957:
2956:
2943:
2936:
2935:
2924:
2918:
2917:
2906:
2898:
2892:
2891:
2881:
2874:
2873:
2862:
2856:
2855:
2845:
2830:
2829:
2820:
2814:
2813:
2803:
2796:
2795:
2784:
2778:
2777:
2767:
2752:
2751:
2742:
2736:
2735:
2726:
2722:
2719:
2712:
2707:
2705:
2700:
2698:
2693:
2692:
2689:
2682:
2678:
2675:
2674:
2662:
2658:
2653:
2648:
2644:
2640:
2636:
2632:
2625:
2618:
2610:
2606:
2601:
2596:
2592:
2588:
2584:
2580:
2576:
2569:
2561:
2557:
2552:
2547:
2542:
2537:
2533:
2529:
2526:(4): 1365â9.
2525:
2521:
2517:
2510:
2502:
2498:
2494:
2490:
2486:
2482:
2478:
2474:
2470:
2466:
2459:
2451:
2447:
2443:
2439:
2435:
2431:
2427:
2423:
2419:
2415:
2407:
2399:
2395:
2390:
2385:
2381:
2377:
2373:
2369:
2365:
2361:
2357:
2350:
2342:
2338:
2334:
2330:
2327:(2): 95â106.
2326:
2322:
2315:
2307:
2303:
2298:
2293:
2289:
2285:
2282:(9): 825â30.
2281:
2277:
2273:
2266:
2258:
2254:
2250:
2246:
2242:
2238:
2234:
2230:
2226:
2219:
2211:
2207:
2202:
2197:
2193:
2189:
2184:
2179:
2175:
2171:
2167:
2160:
2158:
2149:
2145:
2140:
2135:
2130:
2125:
2121:
2117:
2113:
2109:
2105:
2098:
2096:
2094:
2085:
2081:
2076:
2071:
2066:
2061:
2057:
2053:
2049:
2042:
2034:
2030:
2025:
2020:
2015:
2010:
2006:
2002:
1999:(5): 1894â9.
1998:
1994:
1990:
1983:
1975:
1971:
1966:
1961:
1958:(3): 1341â8.
1957:
1953:
1949:
1942:
1934:
1930:
1925:
1920:
1915:
1910:
1906:
1902:
1899:(8): 2762â6.
1898:
1894:
1890:
1883:
1875:
1871:
1866:
1861:
1858:(2): 528â35.
1857:
1853:
1849:
1842:
1834:
1830:
1826:
1822:
1818:
1814:
1810:
1806:
1799:
1791:
1787:
1782:
1777:
1773:
1769:
1765:
1758:
1750:
1746:
1741:
1736:
1732:
1728:
1724:
1720:
1716:
1709:
1701:
1697:
1692:
1687:
1682:
1677:
1673:
1669:
1665:
1661:
1657:
1650:
1642:
1638:
1633:
1628:
1624:
1620:
1616:
1612:
1608:
1604:
1600:
1593:
1585:
1581:
1576:
1571:
1567:
1563:
1559:
1555:
1551:
1544:
1536:
1532:
1527:
1522:
1518:
1514:
1511:(1): 148â56.
1510:
1506:
1499:
1491:
1485:
1480:
1479:
1470:
1468:
1466:
1464:
1462:
1453:
1449:
1445:
1441:
1437:
1433:
1426:
1418:
1414:
1410:
1406:
1402:
1398:
1394:
1390:
1386:
1379:
1371:
1367:
1362:
1357:
1353:
1349:
1345:
1341:
1337:
1333:
1329:
1322:
1314:
1310:
1305:
1300:
1296:
1292:
1288:
1281:
1273:
1269:
1264:
1259:
1255:
1251:
1247:
1243:
1239:
1232:
1224:
1220:
1216:
1212:
1208:
1204:
1200:
1196:
1189:
1181:
1177:
1173:
1169:
1165:
1161:
1153:
1145:
1141:
1136:
1131:
1127:
1123:
1119:
1112:
1110:
1101:
1097:
1092:
1087:
1082:
1077:
1073:
1069:
1065:
1058:
1056:
1054:
1045:
1041:
1036:
1031:
1027:
1023:
1019:
1015:
1011:
1004:
996:
992:
988:
984:
980:
976:
972:
968:
961:
953:
949:
944:
939:
935:
931:
927:
920:
912:
908:
904:
900:
893:
885:
881:
877:
873:
869:
865:
861:
857:
850:
842:
836:
832:
827:
826:
817:
809:
805:
800:
795:
791:
787:
783:
779:
775:
768:
764:
757:
755:
751:
750:
745:
744:
739:
738:
733:
732:
731:Streblomastix
727:
723:
719:
705:
701:
699:
688:
686:
675:
673:
659:
650:
648:
644:
640:
636:
632:
628:
624:
609:
607:
603:
598:
594:
585:
583:
579:
575:
571:
562:
560:
550:
548:
538:
536:
532:
528:
517:
514:
510:
500:
497:
488:
486:
482:
478:
474:
464:
461:
457:
453:
452:fasting state
448:
444:
434:
432:
428:
424:
419:
414:
412:
404:
400:
396:
392:
387:
383:
380:
365:
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327:
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321:
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308:
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274:
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226:
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217:
214:
211:
209:
205:
202:
199:
197:
193:
188:
184:
181:
177:
174:
172:
171:Gene Ontology
168:
165:
162:
159:
156:
153:
149:
146:
143:
141:
137:
134:
131:
129:
125:
122:
119:
117:
113:
110:
109:NiceZyme view
107:
105:
101:
98:
95:
93:
89:
86:
83:
81:
77:
72:
69:
66:
64:
60:
57:
54:
52:
48:
43:
37:
30:
25:
20:
4842:Translocases
4839:
4826:
4813:
4800:
4787:
4777:Transferases
4774:
4761:
4618:Binding site
4520:
4498:
4473:
4094:
4059:
3817:Class I PI 3
3791:
3782:Pantothenate
3653:2.7.1-2.7.4:
3637:Transferases
3464:oxaloacetate
3432:
3229:
3204:
3203:
3181:
3132:
3110:
3092:
3070:
3036:
3014:
2972:
2950:
2930:
2914:
2904:
2888:
2868:
2852:
2826:
2810:
2790:
2774:
2748:
2732:
2634:
2630:
2617:
2582:
2578:
2568:
2523:
2519:
2509:
2468:
2464:
2458:
2417:
2413:
2406:
2363:
2359:
2349:
2324:
2320:
2314:
2279:
2275:
2265:
2232:
2228:
2218:
2173:
2169:
2111:
2107:
2055:
2051:
2041:
1996:
1992:
1982:
1955:
1951:
1941:
1896:
1892:
1882:
1855:
1851:
1841:
1808:
1804:
1798:
1771:
1767:
1757:
1722:
1719:Biochemistry
1718:
1708:
1663:
1659:
1649:
1606:
1602:
1592:
1557:
1553:
1543:
1508:
1504:
1498:
1478:Biochemistry
1477:
1435:
1432:Biochemistry
1431:
1425:
1392:
1388:
1378:
1335:
1331:
1321:
1294:
1290:
1280:
1245:
1241:
1231:
1198:
1194:
1188:
1166:(1): 28â44.
1163:
1159:
1152:
1125:
1121:
1071:
1067:
1017:
1013:
1003:
970:
967:Biochemistry
966:
960:
933:
929:
919:
902:
898:
892:
862:(2): 193â6.
859:
855:
849:
824:
816:
781:
777:
767:
747:
741:
735:
729:
715:
712:Alternatives
694:
681:
670:
656:
627:mitochondria
620:
591:
568:
556:
547:futile cycle
544:
523:
506:
494:
470:
440:
415:
408:
376:
357:
341:
335:
333:
309:
286:
236:
235:
97:BRENDA entry
4613:Active site
4368:Transposase
4358:Recombinase
4003:-nucleoside
3829:Sphingosine
3337:Glucokinase
2235:: 133â151.
1526:10261/78345
749:Trichomonas
531:epinephrine
427:lactic acid
85:IntEnz view
45:Identifiers
4901:Glycolysis
4885:Categories
4816:Isomerases
4790:Hydrolases
4657:Regulation
4170:Telomerase
4013:Polymerase
3787:Mevalonate
3750:Riboflavin
3641:phosphorus
3564:Regulatory
3493:Cori cycle
3384:(Aldolase
3321:Hexokinase
3310:Glycolysis
3296:glycolysis
3288:Metabolism
2750:Hexokinase
2718:Glycolysis
760:References
617:Deficiency
473:hexokinase
467:Regulation
373:Glycolysis
354:glycolysis
344:(Uniprot:
245:glycolysis
154:structures
121:KEGG entry
68:9001-59-6
4695:EC number
4362:Integrase
4286:3' to 5'
3931:Guanylate
3926:Uridylate
3916:Adenylate
3760:Thymidine
3755:Shikimate
3136:hydratase
2934:isomerase
2794:isomerase
2249:1532-8600
2192:1664-8021
2058:(1): 72.
1833:205030574
1811:: 48â53.
1768:Structure
1417:205296677
743:Entamoeba
726:eukaryote
649:(CNSHA).
643:hemolysis
635:TCA cycle
580:(T3) and
533:activate
423:TCA cycle
393:(PEP) to
259:(PEP) to
249:catalyzes
74:Databases
4891:EC 2.7.1
4719:Kinetics
4643:Cofactor
4606:Activity
4296:RNase PH
3904:acceptor
3885:Creatine
3878:acceptor
3850:acceptor
3792:Pyruvate
3777:Glycerol
3738:Platelet
3713:Galacto-
3684:acceptor
3537:glycerol
3364:Platelet
3234:Pyruvate
3008:NADH + H
2988:NADH + H
2872:aldolase
2661:17071828
2609:23178880
2501:12776382
2450:16111842
2442:18337823
2398:22052977
2341:19519368
2306:26087744
2257:28403938
2210:31275349
2148:11698644
2084:23837608
2033:20133837
1825:29775756
1749:25629396
1700:25713368
1641:23064226
1584:27227511
1452:11669648
1409:28338685
1370:20441757
1223:45447144
1144:10751408
1100:29468140
1044:20978194
995:24625677
987:15996096
808:20857498
722:bacteria
600:binding
582:glucagon
527:glucagon
399:pyruvate
368:Reaction
320:splicing
289:isozymes
277:pyruvate
265:pyruvate
225:proteins
213:articles
201:articles
158:RCSB PDB
56:2.7.1.40
4875:Biology
4829:Ligases
4599:Enzymes
4247:PrimPol
4232:Primase
3706:Hepatic
3701:Fructo-
3513:alanine
3489:lactate
3428:Enolase
3303:enzymes
3140:enolase
2734:Glucose
2652:1694820
2600:3511602
2560:5260939
2528:Bibcode
2493:4734564
2473:Bibcode
2465:Science
2422:Bibcode
2389:3471535
2368:Bibcode
2360:Science
2297:5053227
2201:6593282
2176:: 472.
2116:Bibcode
2075:3710280
2024:2838216
2001:Bibcode
1974:8504825
1901:Bibcode
1790:9519410
1740:5286843
1691:4364213
1668:Bibcode
1632:3894725
1611:Bibcode
1575:5115163
1535:4729424
1361:2862152
1340:Bibcode
1313:7493933
1272:8655535
1215:8577250
1180:8230205
1091:5808394
1035:2982937
952:3020052
911:1532331
884:3262531
876:2379684
799:3005776
737:Giardia
574:insulin
447:glucose
431:ethanol
379:enolate
358:E. coli
342:E. coli
337:E. coli
316:introns
314:and 11
305:alanine
239:is the
180:QuickGO
145:profile
128:MetaCyc
63:CAS no.
4861:Portal
4803:Lyases
4534:2.7.13
4512:2.7.12
4487:2.7.11
4462:2.7.10
4301:PNPase
4269:PNPase
4225:POLRMT
4220:ssRNAP
3733:Muscle
3696:Gluco-
3660:kinase
3588:PFKFB4
3584:PFKFB3
3580:PFKFB2
3576:PFKFB1
3360:Muscle
3168:
3147:
3002:NAD+ P
2982:NAD+ P
2683:(MeSH)
2659:
2649:
2607:
2597:
2558:
2551:223473
2548:
2499:
2491:
2448:
2440:
2414:Nature
2396:
2386:
2339:
2304:
2294:
2255:
2247:
2208:
2198:
2190:
2146:
2136:
2082:
2072:
2031:
2021:
1972:
1933:183209
1931:
1924:430732
1921:
1874:188818
1872:
1831:
1823:
1788:
1747:
1737:
1698:
1688:
1639:
1629:
1603:Nature
1582:
1572:
1533:
1486:
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1415:
1407:
1368:
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1263:178107
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950:
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874:
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796:
746:, and
606:ChREBP
593:ChREBP
273:kinase
241:enzyme
208:PubMed
190:Search
176:AmiGO
164:PDBsum
104:ExPASy
92:BRENDA
80:IntEnz
51:EC no.
4755:Types
4382:2.7.8
4351:Other
3990:2.7.7
3950:2.7.6
3895:2.7.4
3872:2.7.3
3844:2.7.2
3728:Liver
3691:Hexo-
3678:2.7.1
3535:from
3511:from
3487:from
3356:Liver
2497:S2CID
2446:S2CID
2139:61106
1829:S2CID
1413:S2CID
1219:S2CID
991:S2CID
880:S2CID
595:is a
312:exons
287:Four
255:from
247:. It
140:PRIAM
4847:list
4840:EC7
4834:list
4827:EC6
4821:list
4814:EC5
4808:list
4801:EC4
4795:list
4788:EC3
4782:list
4775:EC2
4769:list
4762:EC1
4521:see
4499:see
4474:see
3848:COOH
3647:2.7)
3441:PKM2
3437:PKLR
3231:2 Ă
3183:2 Ă
3112:2 Ă
3072:2 Ă
3016:2 Ă
2952:2 Ă
2657:PMID
2605:PMID
2556:PMID
2489:PMID
2438:PMID
2394:PMID
2337:PMID
2302:PMID
2253:PMID
2245:ISSN
2206:PMID
2188:ISSN
2144:PMID
2080:PMID
2029:PMID
1970:PMID
1929:PMID
1870:PMID
1821:PMID
1805:Gene
1786:PMID
1745:PMID
1696:PMID
1637:PMID
1580:PMID
1531:PMID
1484:ISBN
1448:PMID
1405:PMID
1366:PMID
1309:PMID
1268:PMID
1211:PMID
1176:PMID
1140:PMID
1096:PMID
1040:PMID
983:PMID
948:PMID
907:PMID
872:PMID
835:ISBN
804:PMID
529:and
350:PykF
346:PykA
297:PKM2
293:PKLR
220:NCBI
161:PDBe
116:KEGG
36:1PKN
4264:PAP
4205:III
4139:/Y
4130:TDT
4111:/X
4103:III
4095:Pfu
4070:/B
4060:Taq
4035:/A
3802:PFP
3772:NAD
3462:to
3366:)â/
3339:)â/
3333:HK3
3329:HK2
3325:HK1
3214:ATP
3211:ADP
3064:ATP
3061:ADP
3047:ATP
3044:ADP
2837:ADP
2834:ATP
2759:ADP
2756:ATP
2647:PMC
2639:doi
2595:PMC
2587:doi
2546:PMC
2536:doi
2481:doi
2469:179
2430:doi
2418:452
2384:PMC
2376:doi
2364:334
2329:doi
2292:PMC
2284:doi
2237:doi
2196:PMC
2178:doi
2134:PMC
2124:doi
2070:PMC
2060:doi
2019:PMC
2009:doi
1997:107
1960:doi
1956:213
1919:PMC
1909:doi
1860:doi
1856:252
1813:doi
1809:668
1776:doi
1735:PMC
1727:doi
1686:PMC
1676:doi
1664:112
1627:PMC
1619:doi
1607:491
1570:PMC
1562:doi
1521:hdl
1513:doi
1440:doi
1397:doi
1356:PMC
1348:doi
1299:doi
1295:270
1258:PMC
1250:doi
1246:178
1203:doi
1168:doi
1164:234
1130:doi
1126:275
1086:PMC
1076:doi
1030:PMC
1022:doi
975:doi
938:doi
934:261
864:doi
831:132
794:PMC
786:doi
479:by
429:or
403:ATP
269:ATP
196:PMC
152:PDB
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