Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells
<p dir="ltr">Leucine is an essential, ketogenic amino acid with proteinogenic, metabolic, and signaling roles. It is readily imported from the bloodstream into the brain parenchyma. Therefore, it could serve as a putative substrate that is complementing glucose for sustaining the met...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2022
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| الموضوعات: | |
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| _version_ | 1864513512378728448 |
|---|---|
| author | Eduard Gondáš (18877708) |
| author2 | Alžbeta Kráľová Trančíková (18877711) Eva Baranovičová (11004732) Jakub Šofranko (18877714) Jozef Hatok (18877717) Bhavani S. Kowtharapu (18877720) Tomáš Galanda (18877723) Dušan Dobrota (18877726) Peter Kubatka (11008854) Dietrich Busselberg (18877729) Radovan Murín (18877732) |
| author2_role | author author author author author author author author author author |
| author_facet | Eduard Gondáš (18877708) Alžbeta Kráľová Trančíková (18877711) Eva Baranovičová (11004732) Jakub Šofranko (18877714) Jozef Hatok (18877717) Bhavani S. Kowtharapu (18877720) Tomáš Galanda (18877723) Dušan Dobrota (18877726) Peter Kubatka (11008854) Dietrich Busselberg (18877729) Radovan Murín (18877732) |
| author_role | author |
| dc.creator.none.fl_str_mv | Eduard Gondáš (18877708) Alžbeta Kráľová Trančíková (18877711) Eva Baranovičová (11004732) Jakub Šofranko (18877714) Jozef Hatok (18877717) Bhavani S. Kowtharapu (18877720) Tomáš Galanda (18877723) Dušan Dobrota (18877726) Peter Kubatka (11008854) Dietrich Busselberg (18877729) Radovan Murín (18877732) |
| dc.date.none.fl_str_mv | 2022-01-24T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/cancers14030585 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Expression_of_3-Methylcrotonyl-CoA_Carboxylase_in_Brain_Tumors_and_Capability_to_Catabolize_Leucine_by_Human_Neural_Cancer_Cells/26095567 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis cancer cells metabolism leucine branched-chain amino acid 3-methylcrotonyl-CoA carboxylase ketone bodies citrate acetyl-CoA |
| dc.title.none.fl_str_mv | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Leucine is an essential, ketogenic amino acid with proteinogenic, metabolic, and signaling roles. It is readily imported from the bloodstream into the brain parenchyma. Therefore, it could serve as a putative substrate that is complementing glucose for sustaining the metabolic needs of brain tumor cells. Here, we investigated the ability of cultured human cancer cells to metabolize leucine. Indeed, cancer cells dispose of leucine from their environment and enrich their media with the metabolite 2-oxoisocaproate. The enrichment of the culture media with a high level of leucine stimulated the production of 3-hydroxybutyrate. When 13C6-leucine was offered, it led to an increased appearance of the heavier citrate isotope with a molar mass greater by two units in the culture media. The expression of 3-methylcrotonyl-CoA carboxylase (MCC), an enzyme characteristic for the irreversible part of the leucine catabolic pathway, was detected in cultured cancer cells and human tumor samples by immunoprobing methods. Our results demonstrate that these cancer cells can catabolize leucine and furnish its carbon atoms into the tricarboxylic acid (TCA) cycle. Furthermore, the release of 3-hydroxybutyrate and citrate by cancer cells suggests their capability to exchange these metabolites with their milieu and the capability to participate in their metabolism. This indicates that leucine could be an additional substrate for cancer cell metabolism in the brain parenchyma. In this way, leucine could potentially contribute to the synthesis of metabolites such as lipids, which require the withdrawal of citrate from the TCA cycle.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancers<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/cancers14030585" target="_blank">https://dx.doi.org/10.3390/cancers14030585</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_2b16384a078ea340ddfd91d9f2081afa |
| identifier_str_mv | 10.3390/cancers14030585 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26095567 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer CellsEduard Gondáš (18877708)Alžbeta Kráľová Trančíková (18877711)Eva Baranovičová (11004732)Jakub Šofranko (18877714)Jozef Hatok (18877717)Bhavani S. Kowtharapu (18877720)Tomáš Galanda (18877723)Dušan Dobrota (18877726)Peter Kubatka (11008854)Dietrich Busselberg (18877729)Radovan Murín (18877732)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical biochemistry and metabolomicsOncology and carcinogenesiscancer cellsmetabolismleucinebranched-chain amino acid3-methylcrotonyl-CoA carboxylaseketone bodiescitrateacetyl-CoA<p dir="ltr">Leucine is an essential, ketogenic amino acid with proteinogenic, metabolic, and signaling roles. It is readily imported from the bloodstream into the brain parenchyma. Therefore, it could serve as a putative substrate that is complementing glucose for sustaining the metabolic needs of brain tumor cells. Here, we investigated the ability of cultured human cancer cells to metabolize leucine. Indeed, cancer cells dispose of leucine from their environment and enrich their media with the metabolite 2-oxoisocaproate. The enrichment of the culture media with a high level of leucine stimulated the production of 3-hydroxybutyrate. When 13C6-leucine was offered, it led to an increased appearance of the heavier citrate isotope with a molar mass greater by two units in the culture media. The expression of 3-methylcrotonyl-CoA carboxylase (MCC), an enzyme characteristic for the irreversible part of the leucine catabolic pathway, was detected in cultured cancer cells and human tumor samples by immunoprobing methods. Our results demonstrate that these cancer cells can catabolize leucine and furnish its carbon atoms into the tricarboxylic acid (TCA) cycle. Furthermore, the release of 3-hydroxybutyrate and citrate by cancer cells suggests their capability to exchange these metabolites with their milieu and the capability to participate in their metabolism. This indicates that leucine could be an additional substrate for cancer cell metabolism in the brain parenchyma. In this way, leucine could potentially contribute to the synthesis of metabolites such as lipids, which require the withdrawal of citrate from the TCA cycle.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancers<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/cancers14030585" target="_blank">https://dx.doi.org/10.3390/cancers14030585</a></p>2022-01-24T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/cancers14030585https://figshare.com/articles/journal_contribution/Expression_of_3-Methylcrotonyl-CoA_Carboxylase_in_Brain_Tumors_and_Capability_to_Catabolize_Leucine_by_Human_Neural_Cancer_Cells/26095567CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260955672022-01-24T06:00:00Z |
| spellingShingle | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells Eduard Gondáš (18877708) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis cancer cells metabolism leucine branched-chain amino acid 3-methylcrotonyl-CoA carboxylase ketone bodies citrate acetyl-CoA |
| status_str | publishedVersion |
| title | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| title_full | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| title_fullStr | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| title_full_unstemmed | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| title_short | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| title_sort | Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis cancer cells metabolism leucine branched-chain amino acid 3-methylcrotonyl-CoA carboxylase ketone bodies citrate acetyl-CoA |