Kynurenate Forming Enzymes in Liver, Kidney and Brain

Kido, Ryo

doi:10.1007/978-1-4684-5952-4_18

Cited by 5 publications

(9 citation statements)

References 28 publications

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“…KYNA is significantly synthesized in the mammalian periphery and also in the CNS, but to a lesser extent [2][3][4][5][6]. Three KATs (KAT I, KAT II, KAT III) have been identified in rat and human brain tissue [7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia

2023

Cell Physiol Biochem

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Background/Aims: Kynurenic acid (KYNA), a tryptophan metabolite along the kynurenine pathway, is an endogenous antagonist of glutamate ionotropic excitatory amino acid (EAA) receptors and the α7 nicotinic acetylcholine receptor (nAChR). The involvement of KYNA in various pathological conditions and during the aging process is significant. KYNA synthesis from L-kynurenine (L-KYN), through the action of several kynurenine aminotransferases (KATs), is present in the central nervous system (CNS) and periphery of mammals. We were interested in investigating the ability of the brain and peripheral organs of Helix pomatia snails to synthesize KYNA, in an in vitro study. In comparative studies between rat and snail, we looked for the synthesis of KYNA in the liver. We then looked for an effect of age on KYNA synthesis. Materials: Ten shell parameters of the Helix pomatia snail were used to establish an Age Rating Scale (ARS), i.e. body weight, shell weight, shell length, width and height, shell opening length and width, lip width, number of shell turns and external shell growth rings. An age of the snails was determined according to the ARS and the snails were divided into three groups, i.e. young, middle and old age. Homogenates of dissected regions, i.e. cerebral ganglia (CG), subpharyngeal ganglia (SG) consisting of pedal, visceral and pleural ganglia, heart and liver, were examined. KYNA was measured by high performance liquid chromatography (HPLC) and KAT activities were measured by an enzymatic method. Results: With respect to ARS, an evaluation of the age of the snails between young (1-2 years), middle (5-7 years) and old (9-13 years) showed significant differences (p<0.001). Analysis of KYNA levels in different snail tissues, i.e. CG, SG, heart and liver, showed an occurrence in the low femtomolar range. Marked and significant increases of KYNA were found in the liver of middle and old age groups. In the SG, KYNA decreased significantly with age. There were no differences in KYNA levels between groups in CG and heart. The lowest KAT activity was found in CG and SG (5 pmol/mg/h), while in heart and liver the values were visibly higher (between 8 and 80 pmol/mg/h). Only in the liver, and exceptionally only for KAT I, the activity increased significantly with age, i.e. up to 14 years. No age-related changes in KAT I, II and III activities were found in CG and SG. Snail liver shows a different pattern of KAT activities compared to the rat liver. Conclusion: Regions of the CNS and periphery of the snail Helix pomatia are able to synthesize KYNA due to KAT activities. In the snail liver, KAT I activity increased with age. Notably, there was no age-related increase in KAT activities in the heart and especially in the CNS of Helix pomatia, indicating significant differences from mammals. A moderate KYNA metabolism in the Helix pomatia snail in the periods studied, up to 14 years, could be a physiological phenomenon that protects organs from possible functional insufficiency due to high KYNA levels, as has been suggested. It is reasonable to search for the factor(s) that could regulate the concentration of KYNA in the body of the snail.

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Section: Introductionmentioning

confidence: 99%

Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia

2023

Cell Physiol Biochem

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“…KYNA’s involvement in human neurodegenerative and neuroinflammatory processes has been well documented,1,12 thus the increased KYNA metabolism is seen in Alzheimer’s patients,13 in patients with subcortical sclerotic encephalopathy,14 in patients infected with HIV-1 virus,15,16 in patients with Schizophrenia17 and also in elderly human subjects 18. KYNA is synthesized by irreversible transamination of L-kynurenine 20,21. In organs of mammalians several aminotransferases convert L-kynurenine into KYNA 21,22.…”

Section: Introductionmentioning

confidence: 99%

“…KYNA is synthesized by irreversible transamination of L-kynurenine 20,21. In organs of mammalians several aminotransferases convert L-kynurenine into KYNA 21,22. In peripheral tissues of rats there are at least four types of proteins which are capable of catalysing the kynurenine-2-oxoacids transamination reaction to produce KYNA 21,22.…”

Section: Introductionmentioning

confidence: 99%

“…In organs of mammalians several aminotransferases convert L-kynurenine into KYNA 21,22. In peripheral tissues of rats there are at least four types of proteins which are capable of catalysing the kynurenine-2-oxoacids transamination reaction to produce KYNA 21,22. In human and rat brain tissues kynurenine aminotransferase I, II and III (KAT I KAT II and KAT III) were described, and significant differences in respect to the regional brain distribution were revealed 13,23–25.…”

Section: Introductionmentioning

confidence: 99%

“…21,22 In peripheral tissues of rats there are at least four types of proteins which are capable of catalysing the kynurenine-2-oxoacids transamination reaction to produce KYNA. 21,22 In human and rat brain tissues kynurenine aminotransferase I, II and III (KAT I KAT II and KAT III) were described, and significant differences in respect to the regional brain distribution were revealed. 13,23–25 KAT I, KAT II and KAT III are capable of synthesizing KYNA, and show different catalytic characteristics, 23–29 which suggests that substantially KAT II and probably KAT III act under physiological conditions, whereas KAT I may have a particular importance in pathological conditions, like in microglia activation.…”

Section: Introductionmentioning

confidence: 99%

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Endogenous Kynurenine Aminotransferases Inhibitor is Proposed to Act as “Glia Depressing Factor” (GDF)

Baran

Kepplinger

Draxler

2010

Int J�Tryptophan�Res

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The endogenous neuroinhibitory amino acid receptor antagonist kynurenic acid (KYNA) has been hypothetically linked to physiological processes and to the pathogenesis of several brain disorders. The aim of this study was to search KYNA metabolism i.e. KYNA levels and enzymes synthesising KYNA kynurenine aminotransferase I and II (KAT I and II) in the central nervous system (CNS) and in the peripheral nervous system. Within the investigated species we found a remarkably low KYNA content (3.4 nM) in piglet’s serum compared to rat and human serum. Furthermore, in contrast to high KAT activity present in rat and human livers, a lack of KAT I and KAT II activity was found in piglet liver and other piglet peripheral organs. Therefore we attempted to find a reason for the absence of KYNA formation in piglet peripheral tissue and we researched to find if KYNA formation in rat liver homogenate (measured under standard assay conditions for KAT activity) can be influenced by the application of piglet tissue homogenates and other body fluids. KYNA formation in rat liver homogenate was investigated in the presence of piglet liver, piglet brain, rat brain and human brain homogenates, and also in the presence of cerebrospinal fluid (CSF) of the control and of Multiple Sclerosis patients. We found a significant and dose dependent reduction of rat liver KAT I and KAT II activities in the presence of piglet brain, piglet liver, and human brain, but not in the presence of rat brain homogenate. Interestingly, CSF of the human control subjects significantly lowered rat liver KAT I activity. Furthermore, the inhibitory effect of CSF of Multiple Sclerosis (MS) patients was significantly weaker when compared to the CSF of control subjects. Our data, for the first time, indicated the presence of active component(s)—depressing factor—in the body, which was able to block KYNA formation. Reduced KAT inhibitory effect by CSF of MS patients would suggest a lowered “depressing factor” level in CSF of MS patients and is possibly responsible for an enhancement of KYNA formation and for glia activation and gliosis in the CNS. Subsequently, two fractions obtained after centrifugation of CSF from patients with Neuroborreliosis showed a significantly different ability to block KAT I activity. The CSF-sediment fraction exerts a stronger inhibitory activity than the CSF-supernatant fraction, supporting further the presence of a depressing factor. For the first time, data revealed and demonstrated the ability of endogenous components to block KYNA’s synthesis. We propose that a glia depressing factor (GDF), which is abundantly present in the body, might simultaneously control glia cell’s KAT activity, respectively KYNA synthesis and also glia proliferation. The mechanism(s) of action, the composition and structure of this factor needs to be further elaborated.

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Liver and Kidney Kynurenine Aminotransferase Activity in Different Strains of Rats

Costa

Ragazzi

Caparrotta

et al. 1999

Advances in Experimental Medicine and Biology

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Kynurenate Forming Enzymes in Liver, Kidney and Brain

Cited by 5 publications

References 28 publications

Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia

Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia

Endogenous Kynurenine Aminotransferases Inhibitor is Proposed to Act as “Glia Depressing Factor” (GDF)

Liver and Kidney Kynurenine Aminotransferase Activity in Different Strains of Rats

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