Last update 01 Nov 2024

kynureninase

Last update 01 Nov 2024

Basic Info

Synonyms

KYNU, kynureninase, L-kynurenine hydrolase

Introduction

Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.

Drugs associated with kynureninase

PEG-KYNase

Target

kynureninase

Mechanism

kynureninase modulators

Active Org.-

Originator Org.

MedImmune Pharma BV [+4]

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with kynureninase

100 Translational Medicine associated with kynureninase

0 Patents (Medical) associated with kynureninase

448

Literatures (Medical) associated with kynureninase

01 Sep 2024·Pediatric Obesity

Neurological‐related proteomic profiling in plasma of children with metabolic healthy and unhealthy overweight/obesity

Article

Author: Plaza-Florido, Abel ; Osuna-Prieto, Francisco J ; Olvera-Rojas, Marcos ; Solis-Urra, Patricio ; Ortega, Francisco B

SummaryObjectiveChildren with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological‐related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers.MethodsIn this cross‐sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety‐two‐protein targeted approach using Olink's® technology was used.ResultsWe identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood–brain barrier) related to brain health.ConclusionOur proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger‐scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery.

01 Aug 2024·Chemico-Biological Interactions

Integrative multi-omics analysis reveals ortho-topolin riboside exhibits anticancer activity by regulating metabolic pathways in radio-resistant triple negative breast cancer cells

Article

Author: Ahn, Junyoung ; Nam, Seung Min ; Cho, Somi Kim ; Kim, Dae Kyeong ; Lee, Ji Won ; Choi, Hyung-Kyoon

Radio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC₅₀) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log₂(FC) of MGLL = -0.13, log₂(FC) of acylglycerol lipase = -1.35, log₂(FC) of glycerol = -0.81), glycolysis (log₂(FC) of EGLN1 = 0.16, log₂(FC) of EGLN1 = 0.62, log₂(FC) of glucose = -0.76, log₂(FC) of lactate = -0.81), and kynurenine pathway (log₂(FC) of KYNU = 0.29, log₂(FC) of kynureninase = 0.55, log₂(FC) of alanine = 0.72). Additionally, proline metabolism (log₂(FC) of PYCR1 = -0.17, log₂(FC) of proline = -0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log₂(FC) of CCN1 = -0.15, log₂(FC) of CCN family member 1 = -1.02) and Rap 1 signaling pathway (log₂(FC) of PARD6B = -0.28, log₂(FC) of PAR6B = -3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients.

01 Aug 2024·Folia Microbiologica

Phylogeny and genomic analysis of Shewanella cutis sp. nov., isolated from freshwater pufferfish

Article

Author: Kujur, Ritu Rani Archana ; Das, Lipika ; Das, Subrata K ; Debnath, Tanmoy

Three closely related, aerobic, Gram-stain-negative, motile, rod-shaped bacterial strains (PS-2^T, PS-17, and PS-19) were isolated from the skin of freshwater pufferfish (Tetraodon cutcutia). Colonies are pinkish-colored. The optimum growth occurred at 28-30 °C, and the pH was 6.5-7. The major cellular fatty acids were C16:1 ω7c, iso-C15.0, C17:1 ω8c, C18:1 ω7c, and C16:0. The predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, and amino lipids. The genome size of strain PS-2^T is 4.8 Mbp, and the G + C content was 46.0%. The major fraction of genes were associated with biological processes (45.64%), followed by molecular function (29.86%) and cellular components (24.49%). The unique genes identified in strain PS-2^T secreted cyanophycinase, UDP-N-acetylglucosamine 2-epimerase, methyltransferase, kynureninase, ADA regulatory protein, biphenyl degradation, thermostable carboxypeptidase 1, tetrathionate respiration, etc. In addition, alanine and glutamate racemases were present. The 16S rRNA gene sequences shared 98.83-99.24% similarity with the closely related type strains of Shewanella. The ANI and AAI of strain PS-2^T with reference type strains of the genus Shewanella were below 95-96%, and the corresponding dDDH values were below 70%. A phylogenetic tree based on 16S rRNA gene sequences and genome-wide core genes revealed that strain PS-2^T clustered with Shewanella oneidensis LMG 19005^T in both phylogenetic trees. Based on the polyphasic analysis, the new isolates (PS-2^T, PS-17, and PS-19) represent a novel species of Shewanella, for which Shewanella cutis sp. nov. is proposed. The type strain is PS-2^T (= TBRC 15838^T = NBRC 115342^T).

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kynureninase

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