利用同位素工具剖析和定量并行代谢途径。
Using isotopic tools to dissect and quantitate parallel metabolic pathways.
机构信息
Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
出版信息
J Am Chem Soc. 2010 May 12;132(18):6309-11. doi: 10.1021/ja100399m.
Abstract
4-Hydroxyacids are ubiquitous in human physiology. They are derived from the drugs of abuse gamma-hydroxybutyrate (GHB), gamma-hydroxypentanoate(GHP), in addition to the omnipresent lipid peroxidation product 4-hydroxy-2-(E)-nonenal (4-HNE). Previously we reported that 4-hydroxyacids are catabolized through two parallel pathways. In this report we detail two isotopic tools that have allowed the dissection of this catabolic process and illustrate how these tools can be used to quantify the relative flux down each pathway. We found that 4-hydroxynonanoate (4-hydroxyacid derived from 4-HNE) is primarly catabolized through a pathway that phosphorylates the C-4 hydroxyl and isomerizes it to a C-3 hydroxy compound, which is catabolized through beta-oxidation.
摘要
4-羟酸在人体生理中普遍存在。它们来源于滥用药物γ-羟基丁酸（GHB）、γ-羟基戊酸（GHP），此外还有无处不在的脂质过氧化产物 4-羟基-2-（E）-壬烯醛（4-HNE）。此前我们报道过，4-羟酸通过两条平行途径进行代谢。在本报告中，我们详细介绍了两种同位素工具，这些工具允许对该代谢过程进行剖析，并说明了如何使用这些工具来定量每条途径的相对通量。我们发现，4-羟基壬酸（由 4-HNE 衍生的 4-羟酸）主要通过一条途径代谢，该途径将 C-4 羟基磷酸化并将其异构化为 C-3 羟基化合物，然后通过β-氧化进行代谢。
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1
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J Biol Chem. 2009 Nov 27;284(48):33521-34. doi: 10.1074/jbc.M109.055665. Epub 2009 Sep 15.
2
Routes to 4-hydroxynonenal: fundamental issues in the mechanisms of lipid peroxidation.
J Biol Chem. 2008 Jun 6;283(23):15539-43. doi: 10.1074/jbc.R800001200. Epub 2008 Feb 19.
3
gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness.
CNS Drugs. 2006;20(12):993-1018. doi: 10.2165/00023210-200620120-00004.
4
Trends in gamma-hydroxybutyrate (GHB) and related drug intoxication: 1999 to 2003.
Ann Emerg Med. 2006 Feb;47(2):177-83. doi: 10.1016/j.annemergmed.2005.10.012. Epub 2005 Dec 28.
5
4-hydroxynonenal as a bioactive marker of pathophysiological processes.
Mol Aspects Med. 2003 Aug-Oct;24(4-5):281-91. doi: 10.1016/s0098-2997(03)00023-2.
6
Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways.
Mol Aspects Med. 2003 Aug-Oct;24(4-5):177-87. doi: 10.1016/s0098-2997(03)00012-8.
7
Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury.
Alcohol Clin Exp Res. 2003 Jun;27(6):1015-22. doi: 10.1097/01.ALC.0000071928.16732.26.
8
4-Hydroxy-2-nonenal: a product and mediator of oxidative stress.
Prog Lipid Res. 2003 Jul;42(4):318-43. doi: 10.1016/s0163-7827(03)00014-6.
9
4-hydroxynonenal detoxification by mitochondrial glutathione S-transferase is compromised by short-term ethanol consumption in rats.
Alcohol Clin Exp Res. 2002 Aug;26(8):1252-8. doi: 10.1097/01.ALC.0000024081.89523.81.
10
4-Hydroxynonenal in the pathomechanisms of oxidative stress.
IUBMB Life. 2000 Oct-Nov;50(4-5):315-21. doi: 10.1080/713803726.
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