Distribution of D-3-aminoisobutyrate-pyruvate aminotransferase in the rat brain

Abe, Masao; Ochi, Shinichiro; Mori, Yoko; Yamazaki, Kiyohiro; Ishimaru, Takashi; Yoshino, Yuta; Fukuhara, Ryuji; Tanimukai, Satoshi; Matsuda, Seiji; Ueno, Shu‐ichi

doi:10.1186/1471-2202-15-53

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The major ADMA-eliminating route involves an enzymatic reaction catabolizing ADMA to citrulline and dimethylamine through ubiquitously localized dimethylarginine dimethylaminohydrolase (DDAH) (Nijveldt et al 2003). Of interest, transamination of ADMA to d-keto-d-( N , N -dimethylguanidino) valeric acid by alanine-glyoxylate aminotransferase 2, distributed throughout the brain, is an additional metabolic pathway of ADMA removal (Abe et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

2016

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Alterations in brain nitric oxide (NO)/cGMP synthesis contribute to the pathogenesis of hepatic encephalopathy (HE). An increased asymmetrically dimethylated derivative of l-arginine (ADMA), an endogenous inhibitor of NO synthases, was observed in plasma of HE patients and animal models. It is not clear whether changes in brain ADMA reflect its increased local synthesis therefore affecting NO/cGMP pathway, or are a consequence of its increased peripheral blood content. We measured extracellular concentration of ADMA and symmetrically dimethylated isoform (SDMA) in the prefrontal cortex of control and thioacetamide (TAA)-induced HE rats. A contribution of locally synthesized dimethylarginines (DMAs) in their extracellular level in the brain was studied after direct infusion of the inhibitor of DMAs synthesizing enzymes (PRMTs), S-adenosylhomocysteine (AdoHcy, 2 mM), or the methyl donor, S-adenosylmethionine (AdoMet, 2 mM), via a microdialysis probe. Next, we analyzed whether locally synthesized ADMA attains physiological significance by determination of extracellular cGMP. The expression of PRMT-1 was also examined. Concentration of ADMA and SDMA, detected by positive mode electrospray LC–DMS–MS/MS, was greatly enhanced in TAA rats and was decreased (by 30 %) after AdoHcy and AdoMet infusion. TAA-induced increase (by 40 %) in cGMP was unaffected after AdoHcy administration. The expression of PRMT-1 in TAA rat brain was unaltered. The results suggest that (i) the TAA-induced increase in extracellular DMAs may result from their effective synthesis in the brain, and (ii) the excess of extracellular ADMA does not translate into changes in the extracellular cGMP concentration and implicate a minor role in brain NO/cGMP pathway control.

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Section: Introductionmentioning

confidence: 99%

Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

2016

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“…Much less is known about the physiological role of AGXT-2 in ADMA metabolism. AGXT-2 is a pyridoxal phosphate-dependent aminotransferase that, in the rat, is expressed at high levels in the kidney [ 25 ] and brain [ 26 ]. AGXT-2 can also utilize ADMA as a donor of amino groups, leading to the formation of DMGV [ 27 – 29 ].…”

Section: Asymmetric Dimethyl L -Arginine (Adma) Amentioning

confidence: 99%

Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?

Czarnecka

Milewski

2016

Neurochem Res

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The methylated derivative of l-arginine, asymmetric dimethylarginine (ADMA) is synthesized in different mammalian tissues including the brain. ADMA acts as an endogenous, nonselective, competitive inhibitor of all three isoforms of nitric oxide synthase (NOS) and may limit l-arginine supply from the plasma to the enzyme via reducing its transport by cationic amino acid transporters. Hepatic encephalopathy (HE) is a relatively frequently diagnosed complex neuropsychiatric syndrome associated with acute or chronic liver failure, characterized by symptoms linked with impaired brain function leading to neurological disabilities. The l-arginine—nitric oxide (NO) pathway is crucially involved in the pathomechanism of HE via modulating important cerebral processes that are thought to contribute to the major HE symptoms. Specifically, activation of this pathway in acute HE leads to an increase in NO production and free radical formation, thus, contributing to astrocytic swelling and cerebral edema. Moreover, the NO-cGMP pathway seems to be involved in cerebral blood flow (CBF) regulation, altered in HE. For this reason, depressed NO-cGMP signaling accompanying chronic HE and ensuing cGMP deficit contributes to the cognitive and motor failure. However, it should be remembered that ADMA, a relatively little known element limiting NO synthesis in HE, may also influence the NO-cGMP pathway regulation. In this review, we will discuss the contribution of ADMA to the regulation of the NO-cGMP pathway in the brain, correlation of ADMA level with CBF and cognitive alterations observed during HE progression in patients and/or animal models of HE.

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Kidney and liver are the main organs of expression of a key metabolic enzyme alanine:glyoxylate aminotransferase 2 in humans

Jarzebska

Georgi

Jabs

et al. 2019

Atherosclerosis Supplements

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Distribution of D-3-aminoisobutyrate-pyruvate aminotransferase in the rat brain

Cited by 3 publications

References 23 publications

Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?

Kidney and liver are the main organs of expression of a key metabolic enzyme alanine:glyoxylate aminotransferase 2 in humans

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