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Fructokinase (/fruc•to•ki•nase/ [-ki´nas]), also known as D-fructokinase or D-fructose (D-mannose) kinase,^[1] is an enzyme (EC 2.7.1.4) of the liver, intestine, and kidney cortex. Fructokinase is in a family of enzymes called transferases, meaning that this enzyme transfers functional groups; it is also considered a phosphotransferase (or, frequently, a kinase) since it specifically transfers a phosphate group.^[1] Fructokinase specifically catalyzes the transfer of a phosphate group from ATP (the substrate) to fructose as the initial step in its utilization.^[1] The main role of fructokinase is in carbohydrate metabolism, more specifically, sucrose and fructose metabolism. The reaction equation is as follows: ATP + D-fructose = ADP + D-fructose 6-phosphate. This is notable because in most tissues this reaction is catalyzed by hexokinase (EC 2.7.1.1).

Role in Plants and Bacteria

Fructokinase has been characterized from various organisms such as pea (Pisum sativum) seeds, avocado (Persera americana) fruit, and maize (Zea mays) kernels, and many more.^[2]

Specifically, fructokinase may also regulate starch synthesis in conjunction with SS, sucrose synthase, which first metabolizes sink tissue in plant tissues such as in potatoes.^[2] There are also two divergent fructokinase genes that are differentially expressed and which also have different enzymatic properties such as those found in tomatoes. In tomatoes, fructokinase 1 (Frk 1) mRNA is expressed at a constant level during fruit development. However, fructokinase 2 (Frk 2) mRNA has a high expression level in young tomato fruit but then decreases during the later stages of fruit development. Frk 2 has a higher affinity for fructose than Frk 1 but Frk 2 activity is inhibited by high levels of fructose, whereas Frk 1 activity is not.^[2]

In Sinorhizobium meliloti, a common gram-soil bacterium, fructokinase is also used in the metabolism of mannitol and sorbitol, in addition to the metabolism of fructose.^[3]

Role in Animals and Humans

In human liver, purified fructokinase, when coupled with aldolase, has been discovered to contribute to an alternative mechanism to produce oxalate from xylitol. In coupled sequence, fructokinase and aldolase produce glycolaldehyde, a precursor to oxalate, from D-xylulose via D-xylulose 1-phosphate.^[4]

In rat liver cells (hepatocytes), GTP is also a substrate of fructokinase. It can be used at a substantial rate by fructokinase. In these isolated hepatocytes, in vivo, when the concentration of ATP falls to about 1 millimole in a short time interval, GTP becomes an important substrate under these specific conditions.^[5] Unlike phosphofructokinase, fructokinase is not inhibited by ATP.^[6]^[7]

Diseases

Fructosuria or hepatic fructokinase deficiency is a rare but benign inherited metabolic disorder.^[8] This condition is caused by a deficiency of fructokinase in the liver. Affected individuals usually display a large blood fructose concentration after the ingestion of fructose, sucrose or sorbitol.^[9] The disease is mainly characterized by the detection of the abnormal excretion of fructose in the urine through a urinalysis. Fructokinase is needed for the synthesis of glycogen, the body's form of stored energy, from fructose. The presence of fructose in the blood and urine may lead to an incorrect diagnosis of diabetes mellitus. Biochemical abnormalities that may lead to the eventual diagnosis of fructosuria are hepatic fructokinase deficiency, levulosuria and ketohexokinase deficiency.

References

^ ^a ^b ^c DBGET ENZYME: 2.7.1.4. Retrieved 2007-05-06
^ ^a ^b ^c Odanaka S, Bennett AB, Kanayama Y (July 2002). "Distinct physiological roles of fructokinase isozymes revealed by gene-specific suppression of Frk1 and Frk2 expression in tomato". Plant Physiol. 129 (3): 1119–26. doi:10.1104/pp.000703. PMC 166506 . PMID 12114566.
^ Gardiol A, Arias A, Cerveñansky C, Gaggero C, Martínez-Drets G (October 1980). "Biochemical characterization of a fructokinase mutant of Rhizobium meliloti". J. Bacteriol. 144 (1): 12–6. PMC 294576 . PMID 6252186.
^ James HM, Bais R, Edwards JB, Rofe AM, Conyers AJ (February 1982). "Models for the metabolic production of oxalate from xylitol in humans: a role for fructokinase and aldolase". The Australian journal of experimental biology and medical science. 60 (Pt 1): 117–22. doi:10.1038/icb.1982.11. PMID 6284103.
^ Phillips MI, Davies DR (15 June 1985). "The mechanism of guanosine triphosphate depletion in the liver after a fructose load. The role of fructokinase". Biochem. J. 228 (3): 667–71. PMC 1145036 . PMID 2992452.
^ Samuel, Varman T (February 2011). "Fructose induced lipogenesis: from sugar to fat to insulin resistance". Trends in Endocrinology and Metabolism. 22 (2): 60–5. doi:10.1016/j.tem.2010.10.003. PMID 21067942. Retrieved 14 February 2014.
^ BRENDA
^ WebMD Children's Health - Fructosuria. Retrieved 2007-05-06
^ Asipu A, Hayward BE, O'Reilly J, Bonthron DT (September 2003). "Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria". Diabetes. 52 (9): 2426–32. doi:10.2337/diabetes.52.9.2426. PMID 12941785.

External links

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

UpToDate Contents

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1. メソアメリカ腎症 mesoamerican nephropathy

English Journal

Cell Wall Invertase Promotes Fruit Set under Heat Stress by Suppressing ROS-Independent Cell Death.

Liu YH1, Offler CE1, Ruan YL2.
Plant physiology.Plant Physiol.2016 Sep;172(1):163-80. doi: 10.1104/pp.16.00959. Epub 2016 Jul 26.
Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop
PMID 27462084

Dietary Fructose and GLUT5 Transporter Activity Contribute to Antipsychotic-Induced Weight Gain.

Palavicino-Maggio CB1, Kuzhikandathil EV2.
Schizophrenia bulletin.Schizophr Bull.2016 Sep;42(5):1270-9. doi: 10.1093/schbul/sbw037. Epub 2016 Apr 7.
Receptors for antipsychotics in the hypothalamus contribute to antipsychotics-induced weight gain; however, many of these receptors are also expressed in the intestine. The role of these intestinally-expressed receptors, and their potential modulation of nutrient absorption, have not been investigat
PMID 27056716

Aging-associated Renal Disease in Mice is Fructokinase Dependent.

Roncal-Jimenez CA1, Ishimoto T2, Lanaspa MA3, Milagres T4, Andres-Hernando A2, Jensen T2, Miyazaki M2, Doke T5, Hayasaki T5, Nakagawa T6, Maruyama S7, Long DA8, Kuwabara M4, Sanchez-Lozada LG9, Kang DH10, Johnson RJ11.
American journal of physiology. Renal physiology.Am J Physiol Renal Physiol.2016 Jul 27:ajprenal.00306.2016. doi: 10.1152/ajprenal.00306.2016. [Epub ahead of print]
Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydra
PMID 27465991

Japanese Journal

Effect of Ethanol on the Expression of Two Fructokinases in Rice Seedlings

Plant Production Science 17(4), 305-310, 2014
NAID 130004699252

Effects of High Nitrogen Supply on the Susceptibility to Coolness at the Young Microspore Stage in Rice (Oryza sativa L.): Gene Expression Analysis in Mature Anthers

Plant Production Science 12(3), 271-277, 2009
NAID 130004462169

好気・嫌気条件下イネ発芽種子における2種類のフルクトキナーゼの特性

Journal of plant research 119(4), 351-356, 2006-07-01
NAID 10018186358

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★リンクテーブル★

リンク元	「解糖系」「代謝系」「フルクトキナーゼ」
拡張検索	「muscle phosphofructokinase deficiency」「liver type phosphofructokinase-1」「muscle type phosphofructokinase-1」「type C phosphofructokinase-1」「fructokinase deficiency」

「解糖系」

Search
PMC	articles
PubMed	articles
NCBI	proteins

Fructokinase
	Fructokinase dimer, Bacillus subtilis
Identifiers
EC number	2.7.1.4
CAS number	9030-51-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
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

「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

「フルクトキナーゼ」

　　[★]

英: fructokinase

-fructokinase

「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

「type C phosphofructokinase-1」

　　[★]

C型ホスホフルクトキナーゼ1

「fructokinase deficiency」

　　[★] フルクトキナーゼ欠乏症

[dbget-1] DBGET ENZYME: 2.7.1.4. Retrieved 2007-05-06

[Odanaka-2] Odanaka S, Bennett AB, Kanayama Y (July 2002). "Distinct physiological roles of fructokinase isozymes revealed by gene-specific suppression of Frk1 and Frk2 expression in tomato". Plant Physiol. 129 (3): 1119–26. doi:10.1104/pp.000703. PMC 166506 . PMID 12114566.

[Gardiol-3] Gardiol A, Arias A, Cerveñansky C, Gaggero C, Martínez-Drets G (October 1980). "Biochemical characterization of a fructokinase mutant of Rhizobium meliloti". J. Bacteriol. 144 (1): 12–6. PMC 294576 . PMID 6252186.

[James-4] James HM, Bais R, Edwards JB, Rofe AM, Conyers AJ (February 1982). "Models for the metabolic production of oxalate from xylitol in humans: a role for fructokinase and aldolase". The Australian journal of experimental biology and medical science. 60 (Pt 1): 117–22. doi:10.1038/icb.1982.11. PMID 6284103.

[Phillips-5] Phillips MI, Davies DR (15 June 1985). "The mechanism of guanosine triphosphate depletion in the liver after a fructose load. The role of fructokinase". Biochem. J. 228 (3): 667–71. PMC 1145036 . PMID 2992452.

[6] Samuel, Varman T (February 2011). "Fructose induced lipogenesis: from sugar to fat to insulin resistance". Trends in Endocrinology and Metabolism. 22 (2): 60–5. doi:10.1016/j.tem.2010.10.003. PMID 21067942. Retrieved 14 February 2014.

[7] BRENDA

[8] WebMD Children's Health - Fructosuria. Retrieved 2007-05-06

[Asipu-9] Asipu A, Hayward BE, O'Reilly J, Bonthron DT (September 2003). "Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria". Diabetes. 52 (9): 2426–32. doi:10.2337/diabetes.52.9.2426. PMID 12941785.

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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案内

案内

fructokinase