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Information on EC 2.5.1.26 - alkylglycerone-phosphate synthase and Organism(s) Homo sapiens and UniProt Accession O00116
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2.5.1.26 alkylglycerone-phosphate synthaseIUBMB Comments
The ester-linked fatty acid of the substrate is cleaved and replaced by a long-chain alcohol in an ether linkage.
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Word Map
- 2.5.1.26
- ether
- shikimate
- dah7ps
- chorismate
- plasmalogens
-
chondrodysplasia
-
rhizomelic
- punctata
- zellweger
- prephenate
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phenylalanine-sensitive
- dhap-at
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4.1.2.15
-
tyrosine-sensitive
-
8-phosphate
- hexadecanol
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5-enolpyruvylshikimate
- d-erythrose
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tryptophan-sensitive
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plasmalogen-deficient
- medicine
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dihydroxyacetone-phosphate
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, alkyl-dhap, alkyl-dihydroxyacetonephosphate synthase, alkylglycerone phosphate synthase, alkyldihydroxyacetonephosphate synthase, alkyl dihydroxyacetone phosphate synthase, alkylglyceronephosphate synthase, alkyldihydroxyacetone phosphate synthase, alkylglycerone-phosphate synthase, alkyl-dihydroxyacetonephosphate-synthase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alkyl DHAP synthetase
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alkyl dihydroxyacetone phosphate synthase
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alkyl dihydroxyacetone phosphate synthetase
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alkyl-DHAP
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alkyldihydroxyacetone phosphate synthase
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alkyldihydroxyacetonephosphate synthase
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alkyldihydroxyacetonephosphate synthetase
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alkylglycerone phosphate synthase
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synthase, alkylglycerone phosphate
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synthetase, alkyldihydroxyacetone phosphate
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ether formation
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SYSTEMATIC NAME
IUBMB Comments
1-acyl-glycerone-3-phosphate:long-chain-alcohol O-3-phospho-2-oxopropanyltransferase
The ester-linked fatty acid of the substrate is cleaved and replaced by a long-chain alcohol in an ether linkage.
CAS REGISTRY NUMBER
COMMENTARY
102484-74-2
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64060-42-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-acyl-glycerone 3-phosphate + a long-chain alcohol
an alkyl-glycerone 3-phosphate + a long-chain acid anion
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-
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?
additional information
additional information
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overview on substrate specificity
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-acyl-glycerone 3-phosphate + a long-chain alcohol
an alkyl-glycerone 3-phosphate + a long-chain acid anion
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-
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3S)-3-(2-fluorophenyl)-N-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)butanamide
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3-(2,6-difluorophenyl)-N-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)butanamide
the inhibitor show higher binding affinity but retains the binding mode observed for (3S)-3-(2-fluorophenyl)-N-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)methyl)butanamide with the second fluorine atom likely enhancing the hydrophobic interactions with the aliphatic residues surrounding the substrate tunnel
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the enzyme is upregulated in multiple types of cancer cells and primary tumors
the enzyme is upregulated in multiple types of cancer cells and primary tumors
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
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AGPS protein level and phosphatidylethanolamine plasmalogen level are decreased in amyloid-beta protein precursor-deficient cells and brains, overview
metabolism
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alkyl-dihydroxyacetonephosphate-synthase, AGPS, is a rate limiting enzyme in plasmalogen synthesis, catalyzing the initial committed step in plasmalogen synthesis, phosphatidylethanolamine plasmalogen de novo synthesis, overview. Plasmalogens are major brain lipids
physiological function
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plasmalogens are decreased as a consequence of Alzheimer's disease and regulated by amyloid-beta precursor protein processing under physiological conditions. Under the pathological situation of Alzheimer's disease, increased amyloid-beta levels lead to increased reactive oxidative species production, reduced AGPS protein and plasmalogen level, overview. Alterations in amyloid precursor protein-dependent changes of AGPS expression result in reduced protein and plasmalogen levels
malfunction
knockdown of enzyme AGPS restores the drug sensitivity in glioma U-87MG/DDP and hepatic carcinoma Hep-G2/ADM cell lines. Silencing of AGPS leads to reduced cellular level of lysophosphatidic acid, lysophosphatidic acid-ether and prostaglandin E2, which can fuel aggressive and progress of cancer. Knockdown of AGPS also results in downregulation of multi-drug resistance proteins and anti-apoptosis proteins
malfunction
mutations in alkylglycerone phosphate synthase cause rhizomelic chondrodysplasia punctata, RCDP type 3 (RCDP3), a genetically heterogeneous autosomal recessive syndrome characterized by congenital cataracts, shortening of the proximal limbs, neurological abnormalities, seizures, growth delays, and severe intellectual disability. RCDP children die in the first decade of life due to respiratory complications, clinical phenotypes. Correlations of RCDP3 and bs2 phenotypes, detailed overview
malfunction
silencing of AGPS leads to reduced cellular level of lysophosphatidic acid, lysophosphatidic acid-ether and prostaglandin E2, which can fuel aggressive and progress of cancer. Effect of AGPS on adhesion, invasion and cell cycle of glioma and hepatic carcinoma cells, overview
malfunction
AGPS silencing suppresses the proliferation and migration potential of glioma U87MG cells, and suppresses the expression of the circular RNAs circ-ubiquitin-associated protein 2, circ-zinc finger protein 292 and circ-homeodomain-interacting protein kinase 3, and the long non-coding RNAs H19 imprinted maternally expressed transcript (non-protein coding), colon cancer-associated transcript 1 (non-protein coding) and hepatocellular carcinoma upregulated long non-coding RNA
malfunction
effects of AGPS silencing and knockout on circRNA expression in the thyroid cancer cell line FRO are investigated using circRNAs microarray
malfunction
knockdown of alkylglycerone-phosphate synthase leads to an overall reduction of ether lipid levels, as well as oncogenic signaling molecules, such as LPAe, PAFe and eicosanoids
metabolism
NF-kappaB and miR-127 may be the mediators of Tudor-SN-regulated AGPS via the mTOR signaling pathway
metabolism
positive correlation between the expression of alkylglycerone phosphate synthase (AGPS) and the malignant phenotype of thyroid cancer cell lines is identified. The inactivation of AGPS is able to decrease the malignancy of cancer, and inhibits tumor growth and invasion. AGPS is able to regulate the expression of circular RNAs (circRNAs), which may be the mechanism of its anticancer activity
physiological function
enzyme AGPS negatively regulates the invasion potential of glioma and hepatic carcinoma cells by modulating the expression of relevant genes and activity of the MAPK pathway. The MAPK signaling pathway is an important cell signaling pathway, involved in the regulation of many fundamental cellular processes
physiological function
the enzyme catalyzes the critical step in ether lipid synthesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ADAS_HUMAN
658
0
72912
Swiss-Prot
other Location (Reliability: 2)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
lentivirus-shRNA mediated AGPS silencing in Hep-G2/ADM and U-87MG/DDP cancer cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
downregulation of alkylglycerone phosphate synthase and circRNAs expression has a significant effect on the regulation of biological functions, including cell adhesion, cell cycle and metabolism in various tumor types
the enzyme is upregulated in multiple types of cancer cells and primary tumors
up-regulated across different types of aggressive cancers such as human breast 231MFP, melanoma C8161, and prostate PC-3 cancers
the amyloid precursor protein intracellular domain increases the expression of the alkyl-dihydroxyacetonephosphate-synthase in vivo and in vitro
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
enzyme AGPS may be a potential glioma and hepatic carcinoma therapeutic target
pharmacology
alkylglycerone phosphate synthase is an oncogene and can be considered as an antitumor drug target. The study designs novel nitrogenous heterocyclic compound improving targetability by computer-aided drug design technology targeting alkylglycerone phosphate synthase. A total of 12 nitrogenous heterocyclic compounds are designed and predicted the absorption, distribution, metabolism and excretion parameters/toxicity. Their activity in terms of proliferation inhibition, cell cycle arrest and apoptosis induction as then measured using an MTS assay and a high-content screening system in U251 cells. The results show that anti-glioma activity is present in several compounds, which is in accordance with the computer prediction. These compounds may be suitable for the development of a glioma therapeutic drug
medicine
medicine
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enzyme levels are strongly reduced in fibroblasts derived from Zellweger syndrome and rhizomelic chondrodysplasia punctata patients
medicine
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in fibroblast cell lines derived from Zellweger syndrome and rhizomelic chondrodysplasia punctata patients enzyme is mainly present as precursor form
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zomer, A.W.M.; de Weerd, W.F.C.; Langeveld, J.; van den Bosch, H.
Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver
Biochim. Biophys. Acta
1170
189-196
1993
Bos taurus, Cavia porcellus, Homo sapiens, Pan troglodytes, Rattus norvegicus
Van den Bosch, H.; de Vet, E.C.J.M.
Alkyl-dihydroxyacetonephosphate synthase
Biochim. Biophys. Acta
1348
35-44
1997
Cavia porcellus, Homo sapiens, Mus musculus
De Vet, E.C.J.M.; Van den Bosch, H.
Alkyl-dihydroxyacetonephosphate synthase
Cell Biochem. Biophys.
32
117-121
2000
Caenorhabditis elegans, Cavia porcellus, Homo sapiens
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Biermann, J.; Gootjes, J.; Wanders, R.J.A.; Van den Bosch, H.
Stability of alkyl-dihydroxyacetonephosphate synthase in human control and peroxisomal disorder fibroblasts
IUBMB Life
48
635-639
1999
Homo sapiens
De Vet, E.C.J.M.; Ijlst, L.; Oostheim, W.; Wanders, R.J.A.; Van Den Bosch, H.
Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome biogenesis disorders and identification of the point mutation underlying a single enzyme deficiency
J. Biol. Chem.
273
10296-10301
1998
Homo sapiens
Grimm, M.O.; Kuchenbecker, J.; Rothhaar, T.L.; Groesgen, S.; Hundsdoerfer, B.; Burg, V.K.; Friess, P.; Mueller, U.; Grimm, H.S.; Riemenschneider, M.; Hartmann, T.
Plasmalogen synthesis is regulated via alkyl-dihydroxyacetonephosphate-synthase by amyloid precursor protein processing and is affected in Alzheimers disease
J. Neurochem.
116
916-925
2011
Homo sapiens, Mus musculus
Zhu, Y.; Liu, X.J.; Yang, P.; Zhao, M.; Lv, L.X.; Zhang, G.D.; Wang, Q.; Zhang, L.
Alkylglyceronephosphate synthase (AGPS) alters lipid signaling pathways and supports chemotherapy resistance of glioma and hepatic carcinoma cell lines
Asian Pac. J. Cancer Prev.
15
3219-3226
2014
Homo sapiens (O00116)
Liegel, R.P.; Ronchetti, A.; Sidjanin, D.J.
Alkylglycerone phosphate synthase (AGPS) deficient mice: models for rhizomelic chondrodysplasia punctate type 3 (RCDP3) malformation syndrome
Mol. Genet. Metab. Rep.
1
299-311
2014
Homo sapiens (O00116), Homo sapiens, Mus musculus (Q8C0I1), Mus musculus, Mus musculus C57/BL6J (Q8C0I1)
Zhu, Y.; Zhu, L.; Lu, L.; Zhang, L.; Zhang, G.; Wang, Q.; Yang, P.
Role and mechanism of the alkylglycerone phosphate synthase in suppressing the invasion potential of human glioma and hepatic carcinoma cells in vitro
Oncol. Rep.
32
431-436
2014
Homo sapiens (O00116), Homo sapiens
Zhang, Y.; Jia, J.; Li, Y.; Chen, Y.G.; Huang, H.; Qiao, Y.; Zhu, Y.
Tudor-staphylococcal nuclease regulates the expression and biological function of alkylglycerone phosphate synthase via nuclear factor-kappaB and microRNA-127 in human glioma U87MG cells
Oncol. Lett.
15
9553-9558
2018
Homo sapiens (O00116), Homo sapiens
Stazi, G.; Battistelli, C.; Piano, V.; Mazzone, R.; Marrocco, B.; Marchese, S.; Louie, S.M.; Zwergel, C.; Antonini, L.; Patsilinakos, A.; Ragno, R.; Viviano, M.; Sbardella, G.; Ciogli, A.; Fabrizi, G.; Cirilli, R.; Strippoli, R.; Marchetti, A.; Tripodi, M.; Nomura, D.K.; Mattevi, A.; Mai, A.; Valent, V.a.l.e.n.t.e.
Development of alkyl glycerone phosphate synthase inhibitors Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells
Eur. J. Med. Chem.
163
722-735
2019
Homo sapiens (O00116), Cavia porcellus (P97275)
Hou, S.; Tan, J.; Yang, B.; He, L.; Zhu, Y.
Effect of alkylglycerone phosphate synthase on the expression profile of circRNAs in the human thyroid cancer cell line FRO
Oncol. Lett.
15
7889-7899
2018
Homo sapiens (O00116), Homo sapiens
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