Last update 01 Nov 2024

CHKA

Last update 01 Nov 2024

Basic Info

Synonyms

CHETK-alpha, CHKA, ChoKα

+ [5]

Introduction

Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:19915674, PubMed:34077757, PubMed:17007874). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:19915674, PubMed:17007874). Has higher activity with choline (PubMed:19915674, PubMed:17007874). May contribute to tumor cell growth (PubMed:19915674). This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (PubMed:34077757). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (PubMed:34077757). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (PubMed:34077757). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (PubMed:34077757).

Drugs associated with CHKA

EB-3D

Target

CHKA

Mechanism

CHKA inhibitors

Active Org.

University Hospital Padova

Originator Org.

University Hospital Padova

Active Indication

Refractory T Acute Lymphoblastic Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MN58b

Target

CHKA x CHKB

Mechanism

CHKA inhibitors [+1]

Active Org.

Instituto De Investigaciones Biomédicas De Córdoba

Originator Org.

Instituto De Investigaciones Biomédicas De Córdoba

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TCD-717

Target

CHKA

Mechanism

CHKA inhibitors

Active Org.-

Originator Org.

Traslational Cancer Drugs Pharma SL

Active Indication-

Inactive Indication

Advanced Malignant Solid Neoplasm

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CHKA

NCT01215864 / CompletedPhase 1

A Multicenter Phase I Study of TCD-717 Given by 4-Hour Intravenous Infusion in Patients With Advanced Solid Tumors

This is a Phase I dose escalation study of TCD-717, a novel drug that is a specific inhibitor of the enzyme choline kinase alpha, in patients with advanced solid tumors. The objectives of this study are to evaluate the safety of the drug and to determine the maximum tolerated dose and appropriate dose for phase II studies. Secondary objectives are to measure the efficacy of TCD-717; and in a substudy to be conducted in the MTD confirmation cohort only, to evaluate the potential correlation between the levels of tumor choline and tumor response to the choline kinase alpha inhibitor, TCD-717, using magnetic resonance spectroscopy. Pharmacokinetics analysis will be performed on patients enrolled in the maximum tolerated dose confirmation cohort.

Start Date01 Jan 2011

Sponsor / Collaborator

Traslational Cancer Drugs Pharma SL

100 Clinical Results associated with CHKA

100 Translational Medicine associated with CHKA

0 Patents (Medical) associated with CHKA

594

Literatures (Medical) associated with CHKA

01 Dec 2024·Cellular and Molecular Life Sciences

Mfsd7b facilitates choline transport and missense mutations affect choline transport function

Article

Author: Nguyen, Long N ; Sukumar, Viresh Krishnan ; Ha, Hoa Thi Thuy ; Nguyen, Dat T ; Cazenave-Gassiot, Amaury ; Nguyen, Toan Q ; Chua, Jonathan Wei Bao ; Lim, Lina Hsiu Kim

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

01 Dec 2024·Poultry Science

Integrative multiomics analysis identifies key genes regulating intramuscular fat deposition during development

Article

Author: Yu, Yang ; zhao, Guiping ; Zhao, Guiping ; Wang, Yongli ; Cui, Huanxian ; Wang, Shubai ; Cai, Richun ; Zhu, Jinmei ; Wen, Jie ; Zheng, Maiqing

Intramuscular fat (IMF) content is an important indicator of livestock and poultry meat quality. Enhancing IMF deposition can significantly improve meat quality. Focusing on the core process of IMF deposition, this study used the Jingxing Yellow (JXY) chickens as a model organism and employed multi-omics approaches, including RNA-sequencing (RNA-seq), Whole-genome bisulfite sequencing (WGBS), and metabolomics, to identify the key genes influencing IMF deposition in chickens during development. The results indicated that the contents of triglycerides (TG) and phospholipids (PLIP) exhibited an upward trend. The TG content did not differ significantly between day 1 (D1) and day 7 (D7), but increased significantly after 35 days (D35) of age. The WGBS results revealed that CpG methylation was the predominant methylation type in the breast muscle tissue of JXY chickens. Integrative analysis of RNA-seq and WGBS identified 50 genes, including PLA2G4F, PALMD, PLSCR5, ARHGEF26, LUM, DCN, TNRC6B, CACNA1C, ROBO1, and MBTPS2, whose methylation levels were significantly negatively correlated with their expression levels. In addition, the combined Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially-expressed metabolites (DEM) and differentially-expressed genes (DEG) converged on the glycerophospholipid metabolism pathway, which was significantly enriched in DEGs such as PLA2G4F, PLA2G15, LPIN1, MBOAT2, DGKH, AGPAT2, and CHKA, as well as DEM like glycerophosphocholine and phosphocholine. Notably, PLA2G4F was identified as a DEG by DNA methylation, suggesting that PLA2G4F could be a key candidate gene influencing IMF deposition during chicken development. These findings are expected to provide a solid theoretical foundation for improving meat quality through targeted genetic and epigenetic interventions.

01 Oct 2024·Poultry Science

Effect of myristic acid supplementation on triglyceride synthesis and related genes in the pectoral muscles of broiler chickens

Article

Author: Zhao, Guiping ; Wang, Yanke ; Liu, Xiaojing ; Wang, Yidong ; Wen, Jie ; Guo, Yuming ; Cui, Huanxian

Fatty acids (FAs) can serve as energy for poultry, maintain normal cell structure and function, and support a healthy immune system. Although the addition of polyunsaturated fatty acids (PUFAs) to the diet has been extensively studied and reported, the mechanism of action of saturated fatty acids (SFAs) remains to be elucidated. We investigated the effect of 0.04% dietary myristic acid (MA) on slaughter performance, lipid components, tissue FAs, and the transcriptome profile in chickens. The results showed that dietary MA had no effect on slaughter performance (body weight, carcass weight, eviscerated weight, and pectoral muscle weight) (P > 0.05). Dietary MA enrichment increased MA (P < 0.001) and triglycerides (TGs) (P < 0.01) levels in the pectoral muscle. The levels of palmitic acid, linoleic acid (LA), arachidonic acid (AA), SFAs, monounsaturated fatty acids (MUFAs), and PUFAs were significantly higher (P < 0.01) in the MA supplementation group compared to the control group. However, there were no significant differences in the ratios of PUFA/SFA and n6/omega-3 (n3) between the two groups. The MA content was positively correlated with the contents of palmitic acid, LA, linolenic acid (ALA), n3, n6, SFAs, and unsaturated fatty acids (UFA). DHCR24, which is known to be involved in steroid metabolism and cholesterol biosynthesis pathways, was found to be a significantly lower in the MA supplementation group compared to the control group (P < 0.05, log2(fold change) = -0.85). Five overlapping co-expressed genes were identified at the intersection between the differential expressed genes and Weighted Gene Co‑expression Network Analysis-derived hub genes associated with MA phenotype, namely BHLHE40, MSL1, PLAGL1, SRSF4, and ENSGALG00000026875. For the TG phenotype, a total of 28 genes were identified, including CHKA, KLF5, TGIF1, etc. Both sets included the gene PLAGL1, which has a negative correlation with the levels of MA and TG. This study provides valuable information to further understand the regulation of gene expression patterns by dietary supplementation with MA and examines at the molecular level the phenotypic changes induced by supplementation with MA.

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