azaserine

Azaserine
Systematic (IUPAC) name
	O-(2-Diazoacetyl)-L-serine
Clinical data
Legal status	?
Identifiers
CAS number	115-02-6
ATC code	None
PubChem	CID 5284344
ChemSpider	16735688
UNII	87299V3Q9W
KEGG	D03032
ChEBI	CHEBI:74846
ChEMBL	CHEMBL1095699
Chemical data
Formula	C5H7N3O4
Mol. mass	173.127 g/mol
	SMILES O=C(OC[C@H](N)C(O)=O)/C=[N+]=[N-];
	InChI InChI=1S/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1 ; Key:MZZGOOYMKKIOOX-VKHMYHEASA-N ;
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アザセリン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/31 03:14:32」(JST)

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[Wiki en表示]

Azaserine is a naturally occurring serine derivative diazo compound with antineoplastic and antibiotic properties deriving from its action as a purinergic antagonist and structural similarity to glutamine. Azazerine acts by competitively inhibiting glutamine amidotransferase, a key enzyme responsible for glutamine metabolism.

Mechanism of Action

Azaserine inhibits the rate limiting step of the metabolic hexosamine pathway and an irreversibly inhibits γ-glutamyltransferase by acting directly at the substrate-binding pocket. Independent of hexosamine pathway inhibition, azaserine has been demonstrated to protect against hyperglycemic endothelial damage by elevating serum concentrations of manganese-superoxide dismutase, directly reducing the concentration of reactive oxygen species.

Azaserine also downregulates the expression of VCAM-1 and ICAM-1 in response to TNF-α, and research indicates that it may have potential in identifying the L-leucine-favoring system transporter in human T-lymphocytes.

Properties

Azaserine has a solubility of 50 mg/mL in water, a melting point of 146-162 °C, a vapor pressure of 1.53x10⁻¹⁰mmHg at 25 °C, and decomposes before melting.^{[citation needed]}

References

Segel, G.B., et al. 1989. J. Biol. Chem. 264: 16399-16402. PMID 2789219
Hull, R.L., et al. 2007. Am. J. Physiol., Cell Physiol. 293: C1586-C1593. PMID 17804609
Wada, K., et al. 2008. J. Mol. Biol. 380: 361-372. PMID 18555071
Rajapakse, A.G., et al. 2009. Am. J. Physiol. Heart Circ. Physiol. 296: H815-H822. PMID 19136606
Angana Gupta Rajapakse, Xiu-Fen Ming, João M. Carvas, and Zhihong Yang. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects. http://ajpheart.physiology.org/content/296/3/H815.full
Lebedeva ZI, Kabanova EA, Berezov TT. 1986 Mar;12(3):413-20. 6-diazo-5-oxo-L-norleucine and azaserine as affinity inhibitors of glutamin(asparagin)ase.

English Journal

Hyperglycemia-induced downregulation of apolipoprotein M expression is not via the hexosamine pathway.

Jiang B1, Zhang X2, Di D1, Luo G3, Shi Y3, Zhang J3, Berggren-Söderlund M4, Nilsson-Ehle P4, Xu N5.
Lipids in health and disease.Lipids Health Dis.2015 Sep 16;14(1):110. doi: 10.1186/s12944-015-0103-5.
BACKGROUND: We previously demonstrated that hyperglycemia could suppress apolipoprotein M (apoM) synthesis both in vivo and in vitro; however, the mechanism of hyperglycemia-induced downregulation of apoM expression is unknown yet.METHODS: In the present study we further examined if hexosamine pathw
PMID 26377577

In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation.

Zimmerman AD1, Harris RB2.
American journal of physiology. Regulatory, integrative and comparative physiology.Am J Physiol Regul Integr Comp Physiol.2015 Mar 15;308(6):R543-55. doi: 10.1152/ajpregu.00347.2014. Epub 2015 Jan 7.
We previously reported that a 2-day peripheral infusion of glucosamine caused leptin resistance in rats, suggesting a role for the hexosamine biosynthetic pathway (HBP) in the development of leptin resistance. Here we tested leptin responsiveness in mice in which HBP activity was stimulated by offer
PMID 25568075

Hexosamine pathway but not interstitial changes mediates glucotoxicity in pancreatic β-cells as assessed by cytosolic Ca2+ response to glucose.

Yanagida K1, Maejima Y, Santoso P, Otgon-Uul Z, Yang Y, Sakuma K, Shimomura K, Yada T.
Aging.Aging (Albany NY).2014 Mar;6(3):207-14.
Hyperglycemia impairs insulin secretion as well as insulin action, being recognized as the glucotoxicity that accelerates diabetes. However, the mechanism underlying the glucotoxicity in pancreatic β-cells is not thoroughly understood. Hyperglycemia alters glucose metabolism within β-cells and int
PMID 24704640