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Phosphofructokinase is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.

The enzyme-catalysed transfer of a phosphoryl group from ATP is an important reaction in a wide variety of biological processes.^[1] One enzyme that utilizes this reaction is phosphofructokinase (PFK), which catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6- bisphosphate, a key regulatory step in the glycolytic pathway.^[2]^[3] It is allosterically inhibited by ATP and allosterically activated by AMP, thus indicating the cell's energetic needs when it undergoes the glycolytic pathway.^[4] PFK exists as a homotetramer in bacteria and mammals (where each monomer possesses 2 similar domains) and as an octomer in yeast (where there are 4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian monomers, possessing 2 similar domains^[3]). This protein may use the morpheein model of allosteric regulation.^[5]

PFK is about 300 amino acids in length, and structural studies of the bacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved in ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound magnesium ion bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6- bisphosphate); and in an 'open' state, the magnesium ion binds only the ADP,^[6] as the 2 products are now further apart. These conformations are thought to be successive stages of a reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react.^[6]

Deficiency in PFK leads to glycogenosis type VII (Tarui's disease), an autosomal recessive disorder characterised by severe nausea, vomiting, muscle cramps and myoglobinuria in response to bursts of intense or vigorous exercise.^[3] Sufferers are usually able to lead a reasonably ordinary life by learning to adjust activity levels.^[3]

Regulation

There are two types of the enzyme:

Type	Synonyms	EC number	Substrate	Product	Subunit genes
Phosphofructokinase 1	6-phosphofructokinase phosphohexokinase	EC 2.7.1.11	Fructose 6-phosphate	Fructose-1,6-bisphosphate	PFKL, PFKM, PFKP
Phosphofructokinase 2	6-phosphofructo-2-kinase	EC 2.7.1.105	Fructose 6-phosphate	Fructose-2,6-bisphosphate	PFKFB1, PFKFB2, PFKFB3, PFKFB4

References

^ Evans PR, Hellinga HW (1987). "Mutations in the active site of Escherichia coli phosphofructokinase". Nature. 327 (6121): 437–439. doi:10.1038/327437a0. PMID 2953977.
^ Wegener G, Krause U (2002). "Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle". Biochem. Soc. Trans. 30 (2): 264–270. doi:10.1042/bst0300264. PMID 12023862.
^ ^a ^b ^c ^d Raben N, Exelbert R, Spiegel R, Sherman JB, Nakajima H, Plotz P, Heinisch J (1995). "Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency". Am. J. Hum. Genet. 56 (1): 131–141. PMC 1801305. PMID 7825568.
^ Garrett, Reginald; Grisham, Reginald (2012). Biochemistry. Cengage Learning. p. 585. ISBN 978-1133106296.
^ T. Selwood; 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.
^ ^a ^b Shirakihara Y, Evans PR (1988). "Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products". J. Mol. Biol. 204 (4): 973–994. doi:10.1016/0022-2836(88)90056-3. PMID 2975709.

External links

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

This article incorporates text from the public domain Pfam and InterPro IPR000023

This biochemistry article is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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1. ホスホフルクトキナーゼ欠損症（糖原病VII型、垂井病） phosphofructokinase deficiency glycogen storage disease vii tarui disease
2. グルコースおよびグリコーゲン代謝の遺伝性疾患の概要 overview of inherited disorders of glucose and glycogen metabolism
3. ホスホグリセリン酸キナーゼ欠損症およびホスホグリセリン酸ムターゼ欠損症 phosphoglycerate kinase deficiency and phosphoglycerate mutase deficiency
4. 小児における溶血性貧血の概要 overview of hemolytic anemias in children
5. 代謝性ミオパチーへのアプローチ approach to the metabolic myopathies

English Journal

Central metabolic pathways of Aureobasidium pullulans CGMCC1234 for pullulan production.

Sheng L1, Liu C2, Tong Q3, Ma M4.
Carbohydrate polymers.Carbohydr Polym.2015 Dec 10;134:333-6. doi: 10.1016/j.carbpol.2015.08.016. Epub 2015 Aug 13.
With the purpose of understanding the metabolic network of Aureobasidium pullulans, the central metabolic pathways were confirmed by the activities of the key enzymes involved in different pathways. The effect of different iodoacetic acid concentrations on pullulan fermentation was also investigated
PMID 26428132

Targeting glycolysis in the malaria parasite Plasmodium Falciparum.

van Niekerk DD1, Penkler G1,2, du Toit F1, Snoep JL1,2,3.
The FEBS journal.FEBS J.2015 Dec 9. doi: 10.1111/febs.13615. [Epub ahead of print]
Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed
PMID 26648082

O-linked N-acetylglucosaminylation of Sp1 interferes with Sp1 activation of glycolytic genes.

Lim K1, Yoon BH2, Ha CH3.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2015 Dec 4;468(1-2):349-53. doi: 10.1016/j.bbrc.2015.10.096. Epub 2015 Oct 22.
Glycolysis, the primary pathway metabolizing glucose for energy production, is connected to the hexosamine biosynthetic pathway (HBP) which produces UDP-N-acetylglucosamine (UDP-GlcNAc), a GlcNAc donor for O-linked GlcNAc modification (O-GlcNAc), as well as for traditional elongated glycosylation. T
PMID 26499076

Japanese Journal

Structures of Burkholderia thailandensis nucleoside kinase : implications for the catalytic mechanism and nucleoside selectivity

Yasutake Yoshiaki,Ota Hiroko,Hino Emisa,Sakasegawa Shin-ichi,Tamura Tomohiro
Acta Crystallographica Section D, Biological Crystallography 67(11), 945-956, 2011-11
… The nucleoside kinase (NK) from the mesophilic Gram-negative bacterium Burkholderia thailandensis (BthNK) is a member of the phosphofructokinase B (Pfk-B) family and catalyzes the Mg^[2+]- and ATP-dependent phosphorylation of a broad range of nucleosides such as inosine (INO), adenosine (ADO) and mizoribine (MZR). …
NAID 120003560612

イネにおける Rhizoctonia solani の感染によって誘導されるPFP及びPFKの活性とmRNAの発現変化

ムトゥクムセンビ,野瀬昭博
日本作物學會紀事 80, 146-147, 2011-08-30
NAID 10029462859

Related Pictures

★リンクテーブル★

リンク元	「解糖系」「ホスホフルクトキナーゼ」「代謝系」「フルクトース6-リン酸」「フルクトース1,6-ビスリン酸」
拡張検索	「muscle phosphofructokinase deficiency」「liver type phosphofructokinase-1」「muscle type phosphofructokinase-1」「deficiency of phosphofructokinase」「type C phosphofructokinase-1」

「解糖系」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Phosphofructokinase
Identifiers
Symbol	Ppfruckinase
Pfam	PF00365
InterPro	IPR000023
PROSITE	PDOC00336
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

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

「ホスホフルクトキナーゼ」

　　[★]

英: phosphofructokinase, PFK
同: ホスホフルクトキナーゼ1 phosphofructokinase-1
関: ホスホフルクトキナーゼ2。解糖系

生体内での調節

乳酸アシドーシスにおいて

重炭酸Naの投与でアシドーシスを補正する場合、HCO3-はphosphofructokinaseの活性を亢進させるので、乳酸アシドーシスを悪化させることがある。

急性呼吸性アルカローシスにいて

血液のpHが上昇するとホスホフルクトキナーゼの活性が亢進するため、血液中のリン酸が細胞内に取り込まれる結果、低リン血症を来すことがある。

解糖系

fructose-6-phosphate－(phosphofructokinase)→fructose-1,6-bisphosphate

臨床関連

糖原病垂井病

「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

「フルクトース6-リン酸」

　　[★]

英: fructose6-phosphate, F6P, fructose 6-phosphate
同: フルクトース6リン酸、フルクトース一リン酸 fructose monophosphate
関

解糖系

glucose-6-phosphate－(phosphohexose isomerase)→fructose-6-phosphate

fructose-6-phosphate－(phosphofructokinase)→fructose-1,6-bisphosphate

「フルクトース1,6-ビスリン酸」

　　[★]

英: fructose 1,6-bisphosphate FBP
同: フルクトース1,6-二リン酸 fructose 1,6-diphosphate
関: [[]]

解糖系

fructose-6-phosphate－(phosphofructokinase)→fructose-1,6-bisphosphate

fructose-1,6-bisphosphate－(aldolase)→glyceraldehyde 3-phosphate + dihydroxyacetone phosphate

「muscle phosphofructokinase deficiency」

　　[★]

筋ホスホフルクトキナーゼ欠損症

関: glycogen storage disease type VII、Tarui disease

「liver type phosphofructokinase-1」

　　[★]

肝臓型ホスホフルクトキナーゼ1、肝ホスホフルクトキナーゼ1

「muscle type phosphofructokinase-1」

　　[★]

筋肉型ホスホフルクトキナーゼ1、筋ホスホフルクトキナーゼ1

「deficiency of phosphofructokinase」

　　[★] ホスホフルクトキナーゼ欠乏症

「type C phosphofructokinase-1」

　　[★]

C型ホスホフルクトキナーゼ1

[PUB00004002-1] Evans PR, Hellinga HW (1987). "Mutations in the active site of Escherichia coli phosphofructokinase". Nature. 327 (6121): 437–439. doi:10.1038/327437a0. PMID 2953977.

[PUB00014238-2] Wegener G, Krause U (2002). "Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle". Biochem. Soc. Trans. 30 (2): 264–270. doi:10.1042/bst0300264. PMID 12023862.

[PUB00000020-3] Raben N, Exelbert R, Spiegel R, Sherman JB, Nakajima H, Plotz P, Heinisch J (1995). "Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency". Am. J. Hum. Genet. 56 (1): 131–141. PMC 1801305. PMID 7825568.

[4] Garrett, Reginald; Grisham, Reginald (2012). Biochemistry. Cengage Learning. p. 585. ISBN 978-1133106296.

[pmid22182754-5] T. Selwood; 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.

[PUB00003237-6] Shirakihara Y, Evans PR (1988). "Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products". J. Mol. Biol. 204 (4): 973–994. doi:10.1016/0022-2836(88)90056-3. PMID 2975709.

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

匿名

検索

案内

案内

phosphofructokinase