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an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
the basic unit of money in Papua New Guinea

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/13 01:02:09」(JST)

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Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP.

Reaction

The pyruvate kinase reaction:

This process also requires a magnesium 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 final product of aerobic glycolysis. However, in anaerobic glycolysis, lactate dehydrogenase will utilize the NADH produced by glyceraldehyde phosphate dehydrogenase to reduce pyruvate to lactate. In humans, there are two pyruvate kinase isozymes: type M (muscle, SwissProt P14618) and type L,R (liver and erythrocyte, SwissProt P30613). The isozymes differ in primary structure and regulation.

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, in general, irreversible under wild-type conditions.

Pyruvate kinase activity is regulated by

Its own substrate PEP and fructose 1,6-bisphosphate, an intermediate in glycolysis, both of which enhance enzymatic activity. Thus, glycolysis is driven to operate faster when more substrate is present.
ATP is a negative allosteric inhibitor. This accounts for parallel regulation with PFK 1.
It is not known whether citrate plays a role in negative allosteric inhibition, however it is believed that acetyl-CoA does.
Alanine, a negative allosteric modulator

This protein may use the morpheein model of allosteric regulation. ^[1]

Like PFK, pyruvate kinase is regulated both by allosteric effectors and by covalent modification (phosphorylation). Pyruvate kinase is activated by F-1,6-BP in the liver, a second example of feedforward stimulation. ATP and alanine (a biosynthetic product of pyruvate) act as allosteric inhibitors of pyruvate kinase.

Liver pyruvate kinase is also regulated indirectly by epinephrine and glucagon, through protein kinase A. This protein kinase phosphorylates liver pyruvate kinase to deactivate it. Muscle pyruvate kinase is not inhibited by epinephrine activation of protein kinase A. Glucagon signals fasting (no glucose available). Thus, glycolysis is inhibited in the liver but unaffected in muscle when fasting. An increase in blood sugar leads to secretion of insulin, which activates phosphoprotein phosphatase I, leading to dephosphorylation and activation of pyruvate kinase. These controls prevent pyruvate kinase from being active at the same time as the enzymes that 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

Distribution of red blood cell abnormalities worldwide

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 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 being converted 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.

Alternatives

A reversible enzyme with a similar function, Pyruvate phosphate dikinase (PPDK), is found in some bacteria and has been transferred to a number of anaerobic eukaryote groups (for example, Streblomastix, Giardia, Entamoeba, and Trichomonas), it seems via horizontal gene transfer on two or more occasions. In some cases, the same organism will have both Pyruvate kinase and PPDK.^[2]

References

^ T. Selwood and E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function.". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.
^ Liapounova, Na; Hampl, V; Gordon, Pm; Sensen, Cw; Gedamu, L; Dacks, Jb (Dec 2006), "Reconstructing the mosaic glycolytic pathway of the anaerobic eukaryote Monocercomonoides" (Free full text), Eukaryotic Cell 5 (12): 2138–46, doi:10.1128/EC.00258-06, ISSN 1535-9778, PMC 1694820, PMID 17071828

External links

Pyruvate kinase at the US National Library of Medicine Medical Subject Headings (MeSH)

Molecular and Cellular Biology portal

UpToDate Contents

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1. ピルビン酸キナーゼ欠損症 pyruvate kinase deficiency
2. 小児における溶血性貧血の概要 overview of hemolytic anemias in children
3. Diagnosis of hemolytic anemia in the adult
4. マラリアの発症機序 pathogenesis of malaria
5. 小児における皮膚蒼白の評価 evaluation of pallor in children

English Journal

Reduction of d-lactate content in sauerkraut using starter cultures of recombinant Leuconostoc mesenteroides expressing the ldhL gene.

Jin Q1, Li L2, Moon JS2, Cho SK2, Kim YJ3, Lee SJ2, Han NS4.
Journal of bioscience and bioengineering.J Biosci Bioeng.2016 May;121(5):479-83. doi: 10.1016/j.jbiosc.2015.09.007. Epub 2015 Oct 21.
The d-form of lactate, which causes metabolic stress upon excessive dietary intake, is mainly produced by Leuconostoc sp., the predominant species in sauerkraut. To shift the metabolic flux of d-lactate from pyruvate to l-lactate, we expressed the l-lactate dehydrogenase (ldhL) gene in Leuconostoc m
PMID 26472127

Diagnosis of Pyruvate Kinase Deficiency.

Gallagher PG1, Glader B2,3.
Pediatric blood & cancer.Pediatr Blood Cancer.2016 May;63(5):771-2. doi: 10.1002/pbc.25922. Epub 2016 Feb 2.
PMID 26836632

Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.

Kager L1,2, Minkov M1,3, Zeitlhofer P4, Fahrner B1, Ratzinger F5, Boztug K1,6, Dossenbach-Glaninger A7, Haas OA1,2,4.
Pediatric blood & cancer.Pediatr Blood Cancer.2016 May;63(5):914-6. doi: 10.1002/pbc.25878. Epub 2016 Jan 5.
We report two children with severe chronic hemolytic anemia, the cause of which was difficult to establish because of transfusion dependency. Reduced erythrocyte pyruvate kinase activity in their asymptomatic parents provided the diagnostic clues for mutation screening of the PKLR gene and revealed
PMID 26728349

Japanese Journal

Changes in activity and transcript level of liver and gill metabolic enzymes during smoltification in wild and hatchery-reared masu salmon (Oncorhynchus masou)

Mizuno Shinya,Urabe Hirokazu,Aoyama Tomoya,Omori Hajime,Iijima Anai,Kasugai Kiyoshi,Torao Mitsuru,Misaka Naoyuki,Koide Nobuhisa,Ueda Hiroshi
Aquaculture 362-363, 109-120, 2012-09-28
… Increases in gill pyruvate kinase activity during smoltification, which were found in wild fish and indicated activation of glycolysis, were not detected in hatchery fish. … On the other hand, there were no remarkable differences in hepatic and gill 3-hydroxyacyl-coenzyme A dehydrogenase related to lipolysis and creatine kinase activities, which operate in resolution of creatine phosphate, during smoltification between hatchery and wild fish. …
NAID 120004930532

Analysis of energy generation and glycolysis pathway in diminazene aceturate-resistant Babesia gibsoni isolate in vitro

Rajapakshage Bandula Kumara Wickramasekara,Yamasaki Masahiro,Murakami Masahiro,Tamura Yu,Lim Sue Yee,Osuga Tatsuyuki,Sasaki Noboru,Nakamura Kensuke,Ohta Hiroshi,Takiguchi Mitsuyoshi
Japanese Journal of Veterinary Research 60(2), 51-61, 2012-08
… Therefore, in the present study, the concentrations of ATP, glucose, lactate, and pyruvate, and the activities of lactate dehydrogenase and pyruvate kinase in the wild-type and DA-resistant isolate of B. … Meanwhile, the concentrations of lactate and pyruvate and the activities of lactate dehydrogenase and pyruvate kinase in the DA-resistant B. …
NAID 120004689049

Related Pictures

★リンクテーブル★

リンク元	「解糖系」「ピルビン酸キナーゼ欠乏症」「代謝系」「ピルビン酸キナーゼ」「PK」
拡張検索	「phosphoenolpyruvate kinase」「pyruvate kinase deficiency」「pyruvate kinase欠損症」
関連記事	「kinase」「pyruvate」

「解糖系」

Search
PMC	articles
PubMed	articles
NCBI	proteins

	Pyruvate kinase with three domains presented in different colors.
Identifiers
EC number	2.7.1.40
CAS number	9001-59-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: glycolytic pathway
同: エムデン-マイヤーホフ経路 Embden-Meyerhof pathway
関: 解糖、TCA回路

CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2OH)H-O- グルコース (OHが↓↓↑↓↑)
CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- グルコース-6-リン酸 (OHが↓↓↑↓↑)
C(CH2OH)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-6-リン酸
C(CH2O-PO3)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-1,6-リン酸

glucose
↓-hexokinase/glucokinase(liver)
glucose 6-phosphate
↓-phosphohexose isomerase
fructose 6-phosphate
↓-phosphofructokinase
fructose 1,6-bisphosphate
↓-aldolase
glyceraldehyde 3-phosphate
↓-glyceraldehyde-3-phosphate dehydrogenase
1,3-bisphosphoglycerate
↓-phosphoglycerate kinase →ATP
3-phosphoglycerate
↓-phosphoglyceate mutase
2-phosphoglycerate
↓-enolase
phosphoenolpyruvate
↓-pyruvate kinase → ATP
pyruvate
　－(pyruvate dehydrogenase)→acetyl-CoA
　－(pyruvate carboxylase)→oxaloacetate－(NADH+H+)→malate

解糖系の酵素 (first aid step1 2006 p.87, FASTEP1_87_酵素一覧.xls)

1	galactokinase	キナーゼ
2	galactose-1-phosphate uridyltransferase	転移酵素
3	hexokinase/glucokinase	キナーゼ
4	glucose-6-phosphatase	ホスファターゼ
5	glucose-6-phosphate dehydrogenase	脱水素酵素
6	transketolase
7	phosphofructokinase	キナーゼ
8	fructose-1,6-bisphosphatase	ホスファターゼ
9	fructokinase	キナーゼ	フルクトキナーゼ
10	aldolase B		アルドラーゼ
11	pyruvate kinase	キナーゼ	ピルビン酸キナーゼ
12	pyruvate dehydrogenase	脱水素酵素	ピルビン酸デヒドロゲナーゼ
13	HMG-CoA reductase	還元酵素	HMG-CoA還元酵素
14	pyruvate carboxylase	カルボキシラーゼ	ピルビン酸カルボキシラーゼ
15	PEP carboxykinase	キナーゼ	PEPカルボキシキナーゼ
16	citrate synthase	合成酵素	クエン酸合成酵素
17	α-ketoglutarate dehydrogenase	脱水素酵素	α-ケトグルタミン酸脱水素酵素
18	ornithine transcarbamylase	転移酵素	オルニチンカルバモイルトランスフェラーゼ

「ピルビン酸キナーゼ欠乏症」

　　[★]

英: pyruvate kinase deficiency PK deficiency, PKD, deficiency of pyruvate kinase, deficiency of PK
同: ピルビン酸キナーゼ欠損症
関: ピルビン酸キナーゼ

first aid step1 2006 p.89

遺伝

常染色体劣性遺伝

病態生理

ピルビン酸キナーゼ pyruvate kinaseの著しい活性低下により赤血球内のATP産生が阻害される　→　ATP欠乏により赤血球の細胞膜よりカリウムが流出して溶血を来す。、

赤血球：ATP、ピルビン酸、NADの減少。2,3-DPGの増加

症状

黄疸、溶血性貧血

USMLE

Q book p.140 39

「代謝系」

　　[★]

英: metabolic pathway
関: 代謝経路

解糖系
TCA回路
電子伝達系
尿酸回路
糖新生経路

1 galactokinase
2 galactose-1-phosphate uridyltransferase
3 hexokinase/glucokinase
4 glucose-6-phosphatase
5 glucose-6-phosphate dehydrogenase
6 transketolase
7 phosphofructokinase
8 fructose-1,6-bisphosphatase
9 fructokinase
10 aldolase B
11 pyruvate kinase
12 pyruvate dehydrogenase
13 HMG-CoA reductase
14 pyruvate carboxylase
15 PEP carboxykinase
16 citrate synthase
17 α-ketoglutarate dehydrogenase
18 ornithine transcarbamylase

「ピルビン酸キナーゼ」

　　[★]

英: pyruvate kinase, PK
同: ホスホエノールピルビン酸キナーゼ phosphoenolpyruvate kinase、ホスホエノールトランスホスホリラーゼ phosphoenol transphosphorylase
関: 解糖系

first aid step1 2006 p.87,89

ピルビン酸の生合成反応

ピルビン酸合成 (ホスホエノールピルビン酸 + ADP　→ ピルビン酸 + ATP)

CH₂-C(OPO₃^2-)-COOH + ADP + H⁺ －(ピルビン酸キナーゼ)→  CH₃-CO-COO^- + ATP

臨床関連

溶血性貧血(ピルビン酸キナーゼ欠乏症？)

「PK」

　　[★]

ピルビン酸キナーゼ pyruvate kinase

「phosphoenolpyruvate kinase」

　　[★] ピルビン酸キナーゼ。ホスホエノールピルビン酸キナーゼ

「pyruvate kinase deficiency」

　　[★] ピルビン酸キナーゼ欠乏症

「pyruvate kinase欠損症」